trimethoprim--sulfamethoxazole-drug-combination and Pneumonia--Pneumocystis

Echinocandins form a new drug class for the treatment of Pneumocystis pneumonia (PCP), but their efficacies have not been confirmed. The objective of this study was to review the all-cause mortality and efficacy of echinocandins combined with trimethoprim/sulfamethoxazole (TMP/SMZ) for the treatment of PCP. A meta-analysis of retrospective case-control studies of echinocandins combined with TMP/SMZ or TMP/SMZ alone for treating adult PCP was performed. Pubmed, Web of Sciences, Cochrane Register of Controlled Trials, and Embase databases were searched from inception to October 20, 2021. The quality of the included studies was assessed using the Newcastle-Ottawa scale (NOS). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a fixed effects model in the meta-analysis to derive pooled estimates of effect size. Five-hundred forty articles were identified and screened, and five studies were included meta-analysis. Echinocandins combined with TMP/SMZ led to a reduction in all-cause mortality of pneumocystis pneumonia (OR = 0.47; 95%CI 0.32-0.71; P = 0.0003), and the total positive response rate of echinocandins combined with TMP/SMZ was higher than that of TMP/SMZ (OR = 2.16; 95%CI 1.46-3.19; P = 0.0001). This meta-analysis based on retrospective case-control studies was first to show that echinocandins combined with TMP/SMZ for the treatment of pneumocystis pneumonia can lead to a reduction in mortality and improvement in treatment response rates. It is suggested that echinocandins may be a good drug for treating PCP.

Topics: Adult; Echinocandins; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci Pneumonia (PCP) is a common cause of opportunistic lung infection and is associated with high mortality in immunocompromised patients. Few reports describe pneumocystis jiroveci as a causative agent of tyrosine kinase inhibitor or blinatumomab related infections. Case presentation A 64-year-old man with philadelphia chromosome positive acute lymphoblastic leukemia (ALL) presented to the intensive care unit with intermittent high fever and shortness of breath. Three cycles of tyrosine kinase inhibitor (TKI) with blinatumomab therapy were given in recent 4 months. Next-generation sequencing of bronchoalveolar lavage fluid and peripheral blood showed pneumocystis jiroveci. After trimethoprim- sulfamethoxazole treatment and subsequent mechanical ventilation, the infection was controlled successfully.. Due to susceptibility and early onset of PCP in ALL patients received TKI combined with blinatumomab therapy, so we should be alert to PCP when pulmonary infection occurred.

Topics: Antibodies, Bispecific; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Protein Kinase Inhibitors; Trimethoprim, Sulfamethoxazole Drug Combination; Tyrosine Kinase Inhibitors

Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human immunodeficiency virus (HIV) infection, organ transplantation, leukemia, and immunosuppressive therapy. Here we describe the rare case of PCP in a non-HIV-infected diabetic patient and find possible reasons for the association through a literature review.. A 65-years-old male was admitted to our hospital due to a 10-year history of abnormal blood glucose levels and edema of both lower extremities for half a month. However, the patient developed a high fever and progressive dyspnea during hospitalization.. The patient had elevated blood sugar levels, a low white blood cell count within normal limits, and severe lymphopenia. His blood G test and lactate dehydrogenase levels increased significantly. Multiple sputa and bronchoalveolar lavage fluid specimens for Pneumocystis jirovecii (PJ) nucleic acid detection were positive. Chest computed tomography scan demonstrated hazy patchy shadows in the lungs suspected to be pulmonary infections. No tumor, transplantation, or an autoimmune disease was found in the examinations. The patient was diagnosed with PCP finally.. A combination of oral trimethoprim-sulfamethoxazole and intravenous caspofungin was administered immediately against PJ. The patient was also treated with noninvasive ventilator-assisted ventilation, subcutaneous insulin, and hemodialysis therapy.. The patient was discharged home finally with a fair general condition and was followed up without respiratory symptoms.. The compromised immunity in HIV-negative patients with diabetes may be related to lymphocyte decrease and dysfunction, which may cause diabetic patients prone to PJ. Although PCP is rare in diabetes, it should be paid attention to the high rate of misdiagnosis and missed diagnosis.

Topics: Aged; Diabetes Mellitus; HIV Infections; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is an opportunistic fungal infection that occurs in people with impaired or suppressed immunity such as patients with human immunodeficiency virus or organ transplant. However, the incidence and characteristics of PCP in the population with long-term hemodialysis is poorly described in the literature.. We present a case of a 50-year-old female patient being transferred to our hospital in February 2022 with a 20-day history of cough and tight breath. She received amoxicillin and cephalosporin anti-infection treatment successively in local hospital but no significant improvement in symptoms. She had a 2-year history of hemodialysis and no relevant transplantation and human immunodeficiency virus infection. She was diagnosed as ANCA associated vasculitis (AAV) and given oral prednisone acetate (20 mg/day) and methotrexate (2.5 mg/week) half a year ago.. Based on the patient's medical history, Lung computerized tomography image, the Next generation sequencing report, the patient was diagnosed with renal failure, anti-neutrophil cytoplasmic antibody associated vasculitis, and Pneumocystis pneumonia.. The dosage of immunosuppressant was reduced due to leucocyte dripping and fever, and antibiotic and antifungal treatment were also given. The patient's lung condition was getting worse and noninvasive ventilator was required to maintain blood oxygen. Blood filtration is used to remove toxins. Ganciclovir and trimethoprim-sulfamethoxazole was used based on the next generation sequencing report.. The patient died of respiratory failure.. The risk of PCP in hemodialysis patients may be higher than that in ordinary population, and the prognosis of patients with immunosuppression may be worse. Dynamic assessment of vasculitis activity is necessary for hemodialysis patients with AAV because infections may obscure lung symptoms of AAV. It is not recommended that hemodialysis patients with long-term immunosuppression should reduce or stop the dosage of immunosuppressive drugs during the treatment because it may aggravate the condition of PCP. There is still no clear conclusion on whether hemodialysis patients need preventive medicine, but the identification of risk factors and early diagnosis and treatment are important for the prognosis of PCP on hemodialysis population.

Topics: Anti-Infective Agents; Female; HIV Infections; HIV Seropositivity; Humans; Immunosuppressive Agents; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in patients without HIV infection. In contrast to PCP in patients infected with HIV, diagnosis is often delayed and illness is associated with increased mortality.. To provide a comprehensive review of clinical presentation, risk factors, diagnostic strategies, and treatment options for PCP in patients without HIV infection.. Web-based literature review on PCP for trials, meta-analyses, and systematic reviews using PubMed. The restriction to the English language was applied.. Common underlying conditions in patients without HIV infection having PCP are haematological malignancies, autoimmune and inflammatory diseases, solid organ or haematopoietic stem cell transplant, and previous corticosteroid exposure. New risk groups include patients receiving monoclonal antibodies and immunomodulating therapies. Patients without HIV infection who have PCP present with rapid onset and progression of pneumonia, increased duration of hospitalization and a significantly higher mortality rate than patients infected with HIV. PCP is diagnosed by a combination of clinical symptoms and radiological as well as mycological features. Results of immunofluorescence microscopy from bronchoalveolar lavage, PCR testing, and computed tomography imaging as well as the evaluation of clinical presentation are required. The established treatment regime consists of trimethoprim and sulfamethoxazole.. Although the number of patients with immunosuppression due to causes different from HIV is increasing, a simultaneous rise in PCP incidence is observed. In the group of patients without HIV infection, rapid onset of symptoms, a more complex course, and a high mortality rate are recorded. Therefore, the time to diagnosis must be as short as possible to initiate effective therapy promptly. This review aims to raise awareness of PCP in an increasingly affected at-risk group and provides clinicians with a practical guide for efficient diagnosis and targeted therapy. Furthermore, it intends to display current inadequacies in research on the topic of PCP.

Topics: Bronchoalveolar Lavage; HIV Infections; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis infection manifests predominantly as an interstitial pneumonia in immunocompromised patients. Diagnostic testing in the appropriate clinical context can be highly sensitive and specific and involves radiographic imaging, fungal biomarkers, nucleic acid amplification, histopathology, and lung fluid or tissue sampling. Trimethoprim-sulfamethoxazole remains the first-choice agent for treatment and prophylaxis. Investigation continues to promote a deeper understanding of the pathogen's ecology, epidemiology, host susceptibility, and optimal treatment and prevention strategies in solid organ transplant recipients.

Topics: Humans; Immunocompromised Host; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

CD19-targeted chimeric antigen receptor (CAR)-T cell therapy involves administration of patient-derived T cells that target B cells, resulting in B-cell depletion and aplasia. In immunity against Pneumocystis jirovecii (Pj), CD4+ T cells and, more recently, B cells, are generally considered important. Antigen presentation by B cells to CD4+ T cells is particularly important. Trimethoprim-sulfamethoxazole (TMP/SMX) for Pj pneumonia (PJP) prophylaxis is generally discontinued when the CD4+ T-cell count is >200/μL. Here we report the first case, to our knowledge, of PJP in a patient with a CD4+ T cell count of >200/μL after CAR-T cell therapy.. A 14-year-old girl developed hemophagocytic lymphohistiocytosis (HLH) after cord blood transplantation (CBT) for relapsed precursor B-cell acute lymphoblastic leukemia (B-ALL). Twenty-one months after CBT, she was diagnosed with combined second relapse in the bone marrow and central nervous system. The patient was treated with CD19-targeted CAR-T cell therapy for the relapse. After CAR-T cell therapy, the patient remained in remission and continued to receive TMP/SMX for PJP prophylaxis. Seven months after CAR-T cell therapy, CD4+ T cells recovered and TMP/SMX was discontinued. The B-cell aplasia persisted. Ten months after CAR-T cell therapy, the patient developed PJP. The patient was also considered to have macrophage hyperactivation at the onset of PJP. Treatment with immunoglobulin, TMP/SMX, and prednisolone was initiated, and the patient's symptoms rapidly ameliorated.. The patient in the present case developed PJP despite a CD4+ T-cell count of >200/μL after CAR-T cell therapy, probably because of inadequate CD4+ T-cell activation caused by B-cell depletion after CAR-T cell therapy and repeated abnormal macrophage immune responses after CBT. It is important to determine the duration of TMP/SMX for prophylaxis after CAR-T cell therapy according to each case, as well as the CD4+ T-cell count.

Topics: Adolescent; CD4-Positive T-Lymphocytes; Cell- and Tissue-Based Therapy; Female; Humans; Pneumonia, Pneumocystis; Receptors, Chimeric Antigen; Recurrence; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Vascular anomalies (VAs) are increasingly being treated with PI3K/AKT/mTOR pathway inhibitors. These drugs have immunosuppressive properties and thus theoretically overexpose patients to opportunistic infections, especially Pneumocystis jirovecii pneumonia (PJP). PJP prophylaxis use lacks consensus. We aimed to investigate the prevalence of PJP in patients receiving mTOR/PI3K/AKT inhibitors for VAs and determine any indication for pneumocystis prophylaxis in this population.. The study was conducted in 2 parts: (1) we sent a survey to a panel of international experts of VAs asking about their use of pneumocystis prophylaxis drugs and (2) we performed a systematic review of the literature of all published cases of patients receiving these drugs for VA to estimate the prevalence of PJP in this population.. Answers from 68 experts were analyzed: 21 (30.9%) answered they always add PJP prophylaxis when prescribing mTOR inhibitors, 20 (29.4%) case-by-case, and 27 (39.7%) never. For the systematic review, among 3,053 reports screened, 217 were included involving 1,189 patients (1,143 received sirolimus, 38 everolimus, 4 alpelisib, 4 miransertib). Among the 1,189 cases, 2 (0.2%) PJP were reported: one under sirolimus and one under everolimus. Thus, the prevalence of PJP was estimated at 0.88 cases/1,000 patients under sirolimus (95% CI: -0.84 to 2.59) and 26.31 cases/1,000 under everolimus (95% CI: -24.58 to 77.18). Patients with PJP never received prophylaxis drugs. We found no PJP cases under alpelisib and miransertib. PJP prophylaxis was given in 218 (18.3%) cases, more frequently for children (91.3 vs. 77.2% in the non-prophylaxis group, p = 0.012), mostly trimethoprim-sulfamethoxazole (186 patients, 85.3%).. Our study shows that even if PJP is a rare event, it may occur in patients with VAs treated with an mTOR inhibitor. Although our results cannot allow for revising guidelines, prophylaxis with TMP-SMX might be appropriate for a subgroup of patients with risk factors for PJP.

Topics: Child; Everolimus; Humans; Immunocompromised Host; MTOR Inhibitors; Phosphatidylinositol 3-Kinases; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; Proto-Oncogene Proteins c-akt; Retrospective Studies; TOR Serine-Threonine Kinases; Trimethoprim, Sulfamethoxazole Drug Combination

(1) Background:

Topics: Cohort Studies; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with inflammatory bowel disease (IBD) are at increased risk of developing Pneumocystis jirovecii pneumonia (PJP) than the general population. Many medications utilized for the treatment of IBD affect the immune system, potentially further increasing the risk of PJP. Recommendations for prophylaxis against PJP in this patient population are based upon limited evidence, and risk factors for PJP development are not well-agreed upon. The purpose of this systematic review was to consolidate and evaluate the evidence for PJP prophylaxis in patients with IBD. An electronic literature search was performed, and 29 studies were included in the review, of which 24 were case reports or case series. Combined data from five cohort studies showed an absolute risk of developing PJP to be 0.07%. The majority of patients who developed PJP were receiving corticosteroids at the time of diagnosis (76%). The number of concomitant immunosuppressants received at time of PJP diagnosis varied from one to four. All studies reporting treatment of PJP utilized sulfamethoxazole-trimethoprim. Of the 27 studies reporting mortality data, 19% of patients died. Given the lack of conclusive data regarding risk factors for PJP development and the overall low incidence of PJP in patients with IBD, it is recommended to assess the patient's risk on a case-by-case basis to determine whether PJP prophylaxis is warranted.

Topics: Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection causing significant morbidity and mortality in immunocompromised patients. The conventional treatment of PJP is sulfamethoxazole-trimethoprim (SMX-TMP) dosed at 15-20 mg/kg/day of the trimethoprim component. Several studies have suggested similar mortality outcomes and an improved adverse effect profile using a lower dose (<15 mg/kg/day) SMX-TMP regimen. Our objective of this meta-analysis was to evaluate the safety and efficacy of lower dose SMX-TMP for PJP pneumonia.. We conducted a systematic review and meta-analysis of the existing literature according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MEDLINE and Embase databases were searched from inception to January 15, 2020, for studies in English evaluating low-dose SMX-TMP (<15 mg/kg/day) compared to conventional dosing for the treatment of PJP. Outcomes evaluated in our meta-analysis include survival and adverse reactions.. After excluding studies that did not meet our inclusion criteria, four studies were analyzed for adverse reactions and three for mortality. Overall, there was no significant difference in mortality between low-dose and conventional-dose SMX-TMP groups (relative risk [RR]: 0.55, 95% confidence interval [CI], 0.18-1.70). There was a significant decrease in the rate of adverse reactions for the low-dose group compared with the conventional-dose group (RR: 0.70, 95% CI, 0.53-0.91).. This meta-analysis shows a significant decrease in adverse reactions and similar mortality rates with lower-dose SMX-TMP compared to conventional dosing. A low-dose SMX-TMP regimen in the treatment of PJP should be considered a viable option as it could potentially decrease treatment discontinuation rates and reduce patient harm.

Topics: Anti-Bacterial Agents; Humans; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pulmonary toxoplasmosis (PT) is an infectious disease that can be fatal if reactivation occurs in the recipients of hematopoietic stem cell transplantation (HSCT) who were previously infected with Toxoplasma gondii. However, whether the toxoplasmosis reactivation is an actual risk factor for patients receiving immunosuppressive therapies without HSCT remains unclear. Therefore, reactivated PT is not typically considered as a differential diagnosis for pneumonia other than in patients with HSCT or human immunodeficiency virus (HIV).. A 77-year-old man presented with fever and nonproductive cough for several days. He was hospitalized due to atypical pneumonia that worsened immediately despite antibiotic therapy. Before 4 months, he was diagnosed with immune thrombocytopenia (ITP) and received corticosteroid therapy. Trimethoprim-sulfamethoxazole (ST) was administered to prevent pneumocystis pneumonia resulting from corticosteroid therapy.. The serological and culture test results were negative for all pathogens except T. gondii immunoglobulin G antibody. Polymerase chain reaction, which can detect T. gondii from frozen bronchoalveolar lavage fluid, showed positive results. Therefore, he was diagnosed with PT.. ST, clindamycin, and azithromycin were administered. Pyrimethamine and sulfadiazine could not be administered because his general condition significantly worsened at the time of polymerase chain reaction (PCR) examination.. The patient died of acute respiratory distress syndrome despite anti-T. gondii treatment. An autopsy revealed a severe organizing pneumonia and a small area of bronchopneumonia.. PT should be considered as a differential diagnosis in patients with pneumonia, particularly in seropositive patients who receive immunosuppressive therapies even for other than HSCT or HIV.

Topics: Adrenal Cortex Hormones; Aged; Humans; Male; Pneumonia, Pneumocystis; Purpura, Thrombocytopenic, Idiopathic; Symptom Flare Up; Thrombocytopenia; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

To ensure the safety of high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT), evidence-based recommendations on infectious complications after HDC/ASCT are given. This guideline not only focuses on patients with haematological malignancies but also addresses the specifics of HDC/ASCT patients with solid tumours or autoimmune disorders. In addition to HBV and HCV, HEV screening is nowadays mandatory prior to ASCT. For patients with HBs antigen and/or anti-HBc antibody positivity, HBV nucleic acid testing is strongly recommended for 6 months after HDC/ASCT or for the duration of a respective maintenance therapy. Prevention of VZV reactivation by vaccination is strongly recommended. Cotrimoxazole for the prevention of Pneumocystis jirovecii is supported. Invasive fungal diseases are less frequent after HDC/ASCT, therefore, primary systemic antifungal prophylaxis is not recommended. Data do not support a benefit of protective room ventilation e.g. HEPA filtration. Thus, AGIHO only supports this technique with marginal strength. Fluoroquinolone prophylaxis is recommended to prevent bacterial infections, although a survival advantage has not been demonstrated.

Topics: Germany; Hematologic Neoplasms; Hematology; Hematopoietic Stem Cell Transplantation; Hepacivirus; Hepatitis B; Hepatitis B Antibodies; Hepatitis B virus; Hepatitis C; Humans; Medical Oncology; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; RNA, Viral; Societies, Medical; Transplantation, Autologous; Trimethoprim, Sulfamethoxazole Drug Combination

There is still no consensus on the optimal management of COVID-19 within the general population due to the emerging evidence base. High-risk groups, including kidney transplant recipients living with HIV present unique additional challenges. Here we discuss two kidney transplant recipients living with HIV with SARS-CoV-2 infection and their clinical course, and review the existing literature for this subset of challenging patients.

Topics: Adult; Anti-Bacterial Agents; Anti-HIV Agents; Atovaquone; CD4 Lymphocyte Count; CD4-CD8 Ratio; COVID-19; Dideoxynucleosides; Female; Glucocorticoids; Graft Rejection; HIV Infections; HIV-1; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Lamivudine; Male; Middle Aged; Mycophenolic Acid; Pneumonia, Pneumocystis; Prednisolone; Raltegravir Potassium; RNA, Viral; SARS-CoV-2; Tacrolimus; Trimethoprim, Sulfamethoxazole Drug Combination

The incidence of Pneumocystis jirovecii pneumonia (PJP) has increased over recent years in patients with systemic autoimmune rheumatic diseases (SARD). PJP prognosis is poor in those receiving immunosuppressive therapy and glucocorticoids in particular. Despite the effectiveness of cotrimoxazole against PJP, the risk of adverse effects remains significant, and no consensus has emerged regarding the need for PJP prophylaxis in SARD patients undergoing immunosuppressor therapies.Objective: To evaluate the efficacy and safety of cotrimoxazole prophylaxis against PJP in SARD adult patients receiving immunosuppressive therapies. Methods: We performed a systematic review, consulting MEDLINE, EMBASE, and Cochrane Library databases up to April 2020. Outcomes covered prevention of PJP, other infections, morbidity, mortality, and safety. The information obtained was summarized with a narrative review and results were tabulated. Of the 318 identified references, 8 were included. Two were randomized controlled trials and six observational studies. The quality of studies was moderate or low. Despite disparities in the cotrimoxazole prophylaxis regimens described, results were consistent in terms of efficacy, particularly with glucocorticoid doses > 20 mg/day. However, cotrimoxazole 400 mg/80 mg/day, prescribed three times/ week, or 200 mg/40 mg/day or in dose escalation, exhibited similar positive performances. Conversely, cotrimoxazole 400 mg/80 mg/day showed higher incidences of withdrawals and adverse effects. Cotrimoxazole prophylaxis against PJP exhibited efficacy in SARD, mainly in patients taking glucocorticoids ≥ 20 mg/day. All cotrimoxazole regimens exposed seemed equally efficacious, although, higher quality trials are needed. Adverse effects were observed 2 months after initiation, particularly with the 400 mg/80 mg/day regimen. Conversely, escalation dosing or 200 mg/40 mg/day regimens appeared better tolerated.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Rheumatic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia is a common opportunistic respiratory infection among children with human immunodeficiency virus and a weakened immune system. The primary infection in immunocompetent patients may be asymptomatic, whereas fever, shortness of breath, night sweats, nonproductive (dry) cough, pneumonia, progressive respiratory distress and apnea are cardinal symptoms of full-blown pneumocystis pneumonia. The diagnosis can be confirmed by histochemical staining of biological specimens or, recently, by polymerase chain reaction. International recommendations indicate that the drug of choice is the intravenously administered trimethoprim-sulfamethoxazole combination. Early diagnosis and appropriate treatment reduce the mortality of the disease. This article briefly highlights the epidemiology of Pneumocystis pneumonia, its diagnosis and therapeutic options in the pediatric population.

Topics: AIDS-Related Opportunistic Infections; Child; Humans; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) has a significant impact on the mortality of immunocompromised patients. It is not known whether the prophylactic application of trimethoprim-sulfamethoxazole (TMP-SMZ) can reduce the incidence of PCP and mortality in the human immunodeficiency virus (HIV)-negative immunodeficient population. The safety profile is also unknown. There have been few reports on this topic. The aim of this study was to systematically evaluate the efficacy and safety of the use of TMP-SMZ for the prevention of PCP in this population of patients from the perspective of evidence-based medicine.. A comprehensive search without restrictions on publication status or other parameters was conducted. Clinical randomized controlled trials (RCTs) or case-control trials (CCSs) of TMP-SMZ used for the prevention of PCP in HIV-negative immunocompromised populations were considered eligible. A meta-analysis was performed using the Mantel-Haenszel fixed-effects model or Mantel-Haenszel random-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and reported.. Of the 2392 records identified, 19 studies (n = 4135 patients) were included. The efficacy analysis results indicated that the PCP incidence was lower in the TMP-SMZ group than in the control group (OR = 0.27, 95% CI (0.10, 0.77), p = 0.01); however, the rate of drug discontinuation was higher in the TMP-SMZ group than in the control group (OR = 14.31, 95% CI (4.78, 42.91), p<0.00001). In addition, there was no statistically significant difference in the rate of mortality between the two groups (OR = 0.54, 95% CI (0.21, 1.37), p = 0.19). The safety analysis results showed that the rate of adverse events (AEs) was higher in the TMP-SMZ group than in the control group (OR = 1.92, 95% CI (1.06, 3.47), p = 0.03).. TMP-SMZ has a better effect than other drugs or the placebo with regard to preventing PCP in HIV-negative immunocompromised individuals, but it may not necessarily reduce the rate of mortality, the rate of drug discontinuation or AEs. Due to the limitations of the research methodologies used, additional large-scale clinical trials and well-designed research studies are needed to identify more effective therapies for the prevention of PCP.

Topics: Adolescent; Adult; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Immunologic Deficiency Syndromes; Male; Middle Aged; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Humans; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity in immunocompromised patients, with a higher mortality in non-HIV than in HIV patients. P. jirovecii is one of the rare transmissible pathogenic fungi and the only one that depends fully on the host to survive and proliferate. Transmissibility among humans is one of the main specificities of P. jirovecii. Hence, the description of multiple outbreaks raises questions regarding preventive care management of the disease, especially in the non-HIV population. Indeed, chemoprophylaxis is well codified in HIV patients but there is a trend for modifications of the recommendations in the non-HIV population. In this review, we aim to discuss the mode of transmission of P. jirovecii, identify published outbreaks of PCP and describe molecular tools available to study these outbreaks. Finally, we discuss public health and infection control implications of PCP outbreaks in hospital setting for in- and outpatients.

Topics: Chemoprevention; Cross Infection; Disease Outbreaks; HIV Infections; Humans; Immunocompromised Host; Infection Control; Mycological Typing Techniques; Pneumocystis carinii; Pneumonia, Pneumocystis; Public Health; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Humans; Immunocompromised Host; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

A fixed dose of trimethoprim-sulphamethoxazole (TMP/SMZ) is the first-line therapy for Pneumocystis jirovecii pneumonia (PJP). Other alternative regiments have shown a suboptimal cure rate. However, TMP/SMZ has been reported to cause haemolyses when administered to patients with G6DP deficiency. PJP might be fatal without treatment. To date, there is still insufficient evidence to manage PJP with TMP/SMZ in G6DP deficiency population.. We report a G6PD-deficient patient with human immunodeficiency virus (HIV) and PJP infection treated successfully with 21 days of high dose TMP/SMZ without any signs and symptoms of haemolysis.. Based on our experience, it is worth to note that despite TMP/SMZ is consider unsafe in patient with pre-existing G6PD-deficiency, it could still be suggested as the initial drug of choice in Taiwanese or southeast Asian population for treating PJP infected HIV patient.

Topics: Adult; Anti-Bacterial Agents; Glucosephosphate Dehydrogenase Deficiency; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Several cases of Pneumocystosis pneumonia (PCP) have been reported in patients with hypercortisolism, mainly in patients with severe ectopic ACTH syndrome (EAS). We report 2 cases of PCP that did not develop until after starting treatment with metyrapone, one of which occurred in an outpatient with Cushing's disease (CD) without pulmonary symptoms before medical treatment for CD. Patient 1 presented as an outpatient with CD and severe hypercortisolism but nonetheless in good general condition. Treatment with metyrapone was started before pituitary surgery. Patient 2 had EAS due to prostate cancer. Respiratory failure in the two patients occurred 4 days and 30 days, respectively, after the start of metyrapone treatment. In both cases, chest CT showed bilateral interstitial infiltrates, and Pneumocystis jirovecii was found on bronchoalveolar lavage (BAL). A literature review was performed to identify risk factors for PCP in patients with CD: we identified 20 other cases of PCP in patients treated for hypercortisolism, including 16 patients with EAS. Ninety percent of patients had free urinary cortisol greater than 6 times the upper limit of normal (ULN). In conclusion, onset of PCP after initiation of anticortisolic therapy is not limited to patients with EAS, and may occur in CD patients with elevated cortisol levels, even if the patient remains in good general condition and has no pulmonary symptoms before treatment. In such patients, routine prophylactic treatment with trimethoprim/sulfamethoxazole (TMP/SMX) should be considered.

Topics: ACTH Syndrome, Ectopic; Adult; Aged; Aged, 80 and over; Cushing Syndrome; Humans; Immunologic Deficiency Syndromes; Male; Metyrapone; Middle Aged; Opportunistic Infections; Outpatients; Pneumonia, Pneumocystis; Premedication; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia is a common opportunistic respiratory infection among children with human immunodeficiency virus and a weakened immune system. The primary infection in immunocompetent patients may be asymptomatic, whereas fever, shortness of breath, night sweats, nonproductive (dry) cough, pneumonia, progressive respiratory distress and apnea are cardinal symptoms of full-blown pneumocystis pneumonia. The diagnosis can be confirmed by histochemical staining of biological specimens or, recently, by polymerase chain reaction. International recommendations indicate that the drug of choice is the intravenously administered trimethoprim-sulfamethoxazole combination. Early diagnosis and appropriate treatment reduce the mortality of the disease. This article briefly highlights the epidemiology of Pneumocystis pneumonia, its diagnosis and therapeutic options in the pediatric population.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Child, Preschool; Humans; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is an opportunistic disease that mainly affects patients with a deficiency of cell-mediated immunity, especially acquired immunodeficiency syndrome (AIDS). The incidence of PCP in these patients has declined substantially owing to the widespread use of antiretroviral therapy and PCP prophylaxis. However, PCP is still a major AIDS-related opportunistic infection, particularly in patients with advanced immunosuppression in whom human immunodeficiency virus type 1 (HIV-1) infection remains undiagnosed or untreated. The clinical manifestations, diagnosis, treatment, and prevention of PCP in patients with HIV-1 infection are addressed in this review.

Topics: Anti-Bacterial Agents; Biomarkers; HIV Infections; HIV-1; Humans; Immunity, Cellular; L-Lactate Dehydrogenase; Mucin-1; Opportunistic Infections; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PcP) has for many years been reported mostly in human immunodeficiency virus-infected patients. Increasingly, it also affects other immunocompromised patients, e.g. after organ or allogeneic stem cell/bone marrow transplantation, patients with hematologic malignancies or autoimmune diseases. The diagnosis of PcP relies on a critical evaluation of clinical symptoms, risk factors, radiologic features and microbiological tests. High dose cotrimoxazole is the most effective therapeutic option. Rapid initiation is essential, since mortality is especially high in patients admitted to intensive care with respiratory failure. This article reviews the current epidemiology of PcP and highlights the diagnostic and therapeutic options. Recommendations for primary and secondary prophylaxis are summarized.

Topics: Anti-Bacterial Agents; HIV Infections; Humans; Immunocompromised Host; Opportunistic Infections; Pneumocystis carinii; Pneumocystis Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PcP), a common and often life-threatening opportunistic infection in HIV-infected patients. However, non-HIV, immunocompromised patients are at risk of PcP as well, whereas the mortality appears to be higher among these patients. Pneumocystis co-infections with other microorganisms are less frequent and only sparse reports of combined PcP and invasive pulmonary fungal infections exist in the literature, especially in the non-HIV patients. Two cases of pulmonary co-infections by P. jirovecii and Aspergillus fumigatus are presented. Both patients were non-HIV infected, the first one was suffering from crescentic IgA nephropathy under immunosuppressive treatment and the second from resistant non-Hodgkin lymphoma under chemotherapy. Both patients were treated with intravenous trimethoprim/sulphamethoxazole (TMP/SMX) combined with voriconazole. The first patient showed gradual clinical improvement while the outcome for the second patient was unfavourable. In addition, a literature review of the previous published cases of co-infection by P. jirovecii and other fungi in non-HIV patients was performed. Our target was to provide comprehensive information on this kind of infections, highlighting the importance of clinical suspicion.

Topics: Adult; Aged, 80 and over; AIDS-Related Opportunistic Infections; Aspergillus fumigatus; Coinfection; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Invasive Fungal Infections; Lung; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Pulmonary Aspergillosis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART), Pneumocystis pneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART. Areas covered: This review summarizes the diagnosis and first-line and alternative treatment and prophylaxis for Pneumocystis pneumonia in HIV-infected patients. Articles for this review were identified through searching PubMed. Search terms included: 'Pneumocystis pneumonia', 'Pneumocystis jirovecii pneumonia', 'Pneumocystis carinii pneumonia', 'trimethoprim-sulfamethoxazole', 'primaquine', 'trimetrexate', 'dapsone', 'pentamidine', 'atovaquone', 'echinocandins', 'human immunodeficiency virus infection', 'acquired immunodeficiency syndrome', 'resistance to sulfamide' and combinations of these terms. We limited the search to English language papers that were published between 1981 and March 2017. We screened all identified articles and cross-referenced studies from retrieved articles. Expert commentary: Trimethoprim-sulfamethoxazole will continue to be the first-line agent for Pneumocystis pneumonia given its cost, availability of both oral and parenteral formulations, and effectiveness or efficacy in both treatment and prophylaxis. Whether resistance due to mutations within dihydropteroate synthase gene compromises treatment effectiveness remains controversial. Continued search for effective alternatives with better safety profiles for Pneumocystis pneumonia is warranted.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Bacterial Proteins; CD4 Lymphocyte Count; Dihydropteroate Synthase; Drug Resistance, Bacterial; HIV-1; Humans; Immunocompromised Host; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia plays an increasing role in patients with autoimmune disorders, due to more intensive immunosuppressive therapy. Humans seem to be the most important pathogen reservoir. Diseases are probably caused by airborne new infections. Cough, subfebrile temperature and dyspnea on exertion are the leading symptoms. In addition to imaging, in particular high-resolution computed tomography, pathogen detection by staining methods or molecular genetic methods plays the decisive role. Trimethoprim and sulfamethoxazole (TMP-SMX) is the most important medication for treatment. Adjuvant corticosteroid treatment is sometimes recommended, but evidence for benefits in patients with rheumatological disorders is not well documented. For patients on high-dose systemic corticosteroid treatment or intensive combined immunosuppression, primary prophylaxis is recommended by many experts. TMP-SMX remains the first-choice preventive treatment in these patients.

Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Bacteriological Techniques; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Opportunistic Infections; Pneumonia, Pneumocystis; Primary Prevention; Risk Factors; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

In recent years, the incidence of Pneumocystis jirovecii pneumonia (PJP) has increased in immunocompromised patients without human immunodeficiency virus (HIV) infection. Chemoprophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is highly effective in preventing PJP in both HIV-positive and -seronegative patients. In HIV-positive patients, the risk of PJP is strongly correlated with decreased CD4 cell count. The role of CD4 cell count in the pathogenesis of PJP in non-HIV immunocompromised patients is less well studied. For most immunosuppressive conditions, no clear guidelines indicate whether to start TMP-SMX.. We conducted a systematic literature review with the aim to provide a comprehensive overview on the role of CD4 cell counts in managing the risk of PJP in HIV-seronegative patients.. Of the 63 individual studies retrieved, 14 studies report on CD4 cell counts in a variety of immunosuppressive conditions. CD4 cell count were <200/μL in 73.1% of the patients.. CD4 cell count <200/μL is a sensitive biomarker to identify non-HIV immunocompromised patients who are at risk for PJP. Measuring CD4 cell counts could help clinicians identify patients who may benefit from TMP-SMX prophylaxis.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotic Prophylaxis; CD4 Lymphocyte Count; HIV Seronegativity; Humans; Immunocompromised Host; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is a ubiquitous fungus, which causes pneumonia in humans. Diagnosis was hampered by the inability to culture the organism, and based on microscopic examination of respiratory samples or clinical presentation. New assays can assist in the diagnosis and even aid with the emergence of resistant infections. Areas covered: This manuscript will provide background information on Pneumocystis pneumonia (PcP). Diagnosis, from radiological to non-microbiological (e.g. Lactate dehydrogenase) and microbiological investigations (Microscopy, PCR, β-D-Glucan) will be discussed. Recommendations on prophylactic and therapeutic management will be covered. Expert commentary: PcP diagnosis using microscopy is far from optimal and false negatives will occur. With an incidence of 1% or less, the pre-test probability of not having PcP is 99% and testing is suited to excluding disease. Microscopy provides a high degree of diagnostic confidence but it is not infallible, and its lower sensitivity limits its application. Newer diagnostics (PCR, β-D-Glucan) can aid management and improve performance when testing less invasive specimens, such as upper respiratory samples or blood, alleviating clinical pressure. Combination testing may allow PcP to be both diagnosed and excluded, and molecular testing can assist in the detection of emerging resistant PcP.

Topics: Antifungal Agents; beta-Glucans; Biomarkers; Dapsone; Disease Management; Humans; Incidence; L-Lactate Dehydrogenase; Microscopy; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Proteoglycans; Radiography, Thoracic; Trimethoprim, Sulfamethoxazole Drug Combination

The presentation of Pneumocystis pneumonia (PCP) in previously healthy men having sex with men (MSM) in San Francisco and New York City in 1981 heralded the beginning of the human immunodeficiency virus (HIV) pandemic. Despite a decreasing incidence of PCP among patients with HIV/AIDS (acquired immunodeficiency syndrome) since the advent of combination antiretroviral therapy in the mid-1990s, PCP remains one of the most common AIDS-defining opportunistic infections in the United States and Western Europe. Newer molecular diagnostic tests in conjunction with standard immunofluorescent or colorimetric tests have allowed for more rapid and accurate diagnosis. Although several effective oral and intravenous therapies exist to treat PCP, mortality rates in HIV-infected individuals remain unacceptably high, especially in those with advanced AIDS. The identification of specific mutations in Pneumocystis genes targeted by trimethoprim-sulfamethoxazole has raised concerns about the development of resistance to the drug of choice and may ultimately lead to greater utilization of alternative therapies to treat PCP in the future.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Resistance, Microbial; HIV Infections; Humans; Molecular Diagnostic Techniques; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG.A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid-base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity.Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX.

Topics: Acidosis, Lactic; Adult; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Propylene Glycol; Solvents; Trimethoprim, Sulfamethoxazole Drug Combination

Summarize data on the pathophysiology, treatment, and prevention options for non-AIDS immunocompromised patients who have Pneumocystis jirovecii pneumonia (PJP); review the epidemiology of patients presenting with PJP; and discuss the first and second-line pharmacological options for treatment and prophylaxis of PJP in this population.. MEDLINE (1989-February 2016) searched. Terms searched included combinations of Pneumocystis jirovecii, Pneumocystis carinii, non-HIV, infected, patients, prevention, prophylaxis, Bactrim, treatment, AIDS, opportunistic, immunocompromised, cancer, and pathophysiology. Articles included had the most relevant information on PJP pathophysiology, and first-/second-line treatment and prophylactic options. Inclusion criteria were met and evaluated with 43 sources.. P jirovecii has a complicated life-cycle; it seeks to find compromised immune systems in order to replicate, causing life-threatening complications. With immunosuppressive medications coming to market for immunomodulating diseases, PJP has become a prevalent opportunistic infection in the non-HIV population. CD4+ lymphocyte count <200 cells/µL is the primary risk factor for PJP presentation in these patients. With data from clinical trials, trimethoprim/sulfamethoxazole (TMP/SMX) has become the primary treatment and prophylaxis of PJP in the non-HIV population, although second-line options are available.. PJP is a health problem that may result in an increased concern as more immunomodulating medications to treat various disease states are developed. Patients on these drugs or those with immunosuppressive diseases should have their CD4+ count monitored. Health care providers should continue to use TMP/SMX as the primary option in non-HIV, immunocompromised patients for treatment and prophylaxis of PJP.

Topics: CD4 Lymphocyte Count; Humans; Immunocompromised Host; Immunosuppressive Agents; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is responsible for Pneumocystis pneumonia (PCP), which occurs almost exclusively in immunocompromised individuals. Trimethoprim-sulfamethoxazole (TMP-SMZ) is regarded as the first-line treatment and prophylaxis for P. jirovecii infection, but the frequency of adverse reactions and newly emerged antibiotic resistance limit its use.. Ulcerations and hemorrhages involving the tongue were noted secondary to TMP-SMZ desensitization against PCP in a 46-year-old male who had previously been diagnosed with IgA nephropathy and sustained prolonged corticosteroid therapy. There was an urgent need for an alternative regimen due to the severe response to TMP-SMZ. The patient was successfully treated with a combination therapy of caspofungin and clindamycin.. Caspofungin combined with clindamycin is an optional treatment for PCP when treatment with TMP-SMZ fails or in patients who cannot tolerate TMP-SMZ.

Topics: Antifungal Agents; Caspofungin; Clindamycin; Echinocandins; Glomerulonephritis, IGA; Humans; Immunocompromised Host; Lipopeptides; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography, Thoracic; Sputum; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia (PCP) is frequently reported in lymphoma patients treated with rituximab-contained regimens. There is a trend toward a difference in PCP risk between bi- and tri-weekly regimens. The aims of this systemic review and meta-analysis were to estimate the risk for PCP in these patients, compare the impact of different regimens on the risk, and evaluate the efficacy of prophylaxis. The cohort studies with incept up to January 2014 were retrieved from the Cochrane Library, Medline, Embase, and Web of Science databases. Studies that compared the incidence of PCP in patients with and without rituximab treatment were conducted. Studies that reported the results of prophylaxis were concentrated to evaluate the efficacy of prophylaxis. Fixed effect Mantel-Haenszel model was chosen as the main analysis method. Funnel plots were examined to estimate the potential selection bias. Egger's test and Begg's test were used for the determination of possible small study bias. Eleven cohort studies that met the inclusion criteria were finally included. Results indicated that rituximab was associated with a significantly increased risk for PCP (28/942 vs 5/977; risk ratio: 3.65; 95% confidence interval 1.65 to 8.07; P=0.001), and no heterogeneity existed between different studies (I2=0%). Little significant difference in PCP risk was found between bi-weekly and tri-weekly regimens (risk ratio: 3.11; 95% confidence interval 0.92 to 10.52, P=0.068). PCP risk was inversely associated with prophylaxis in patients treated with rituximab (0/222 vs 26/986; risk ratio: 0.28; 95% confidence interval 0.09 to 0.94; P=0.039). In conclusion, PCP risk was increased significantly in lymphoma patients subjected to rituximab-contained chemotherapies. Difference in PCP risk between bi-weekly and tri-weekly regimens was not significant. Additionally, prophylaxis was dramatically effective in preventing PCP in rituximab-received lymphoma patients, suggesting that rituximab should be recommended for these patients.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Humans; Incidence; Lymphoma; Odds Ratio; Pneumocystis carinii; Pneumonia, Pneumocystis; Publication Bias; Rituximab; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Humans; Immunocompromised Host; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is the only fungus of its kind to be pathogenic in humans. It is primarily responsible for pneumonia (PJP). The key to understanding immune defences has focused on T-cells, mainly because of the HIV infection epidemic. Patients presenting with PJP all have a CD4 count below 200/mm(3). The introduction of systematic primary prophylaxis and the use of new anti-retroviral drugs have significantly reduced the incidence of this disease in the HIV-infected population, mainly in developed countries. The increasingly frequent use of corticosteroids, chemotherapy, and other immunosuppressive drugs has led to an outbreak of PJP in patients not infected by HIV. These patients presenting with PJP have more rapid and severe symptoms, sometimes atypical, leading to delay the initiation of a specific anti-infective therapy, sometimes a cause of death. However, the contribution of new diagnostic tools and a better understanding of patients at risk should improve their survival.

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; beta-Glucans; Connective Tissue Diseases; Drug Therapy, Combination; Early Diagnosis; HIV Seronegativity; Humans; Immunocompromised Host; Immunologic Deficiency Syndromes; Immunologic Factors; Immunosuppressive Agents; Neoplasms; Organ Transplantation; Pneumocystis carinii; Pneumocystis Infections; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Postoperative Complications; Prognosis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PJP) is an important opportunistic infection that has been increasingly reported in patients with rheumatic disease. Reported incidence among patients taking TNF inhibitors (TNFi) has varied, but has usually been low. Still, disease causes significant mortality among those affected and must be considered in patients with rheumatological disease presenting with dyspnea and cough. Diagnosis can be difficult in the non-HIV population, and our understanding of the epidemiology and natural history after exposure is changing. Trimethoprim-sulfamethoxazole is believed to be the most effective agent for treatment and prophylaxis, but is associated with significant adverse effects. Given the low incidence reported in most studies of patients on TNFi, prophylaxis is probably not beneficial for this patient population as a whole.

Topics: Antirheumatic Agents; Chemoprevention; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Rheumatic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

Pneumocystis pneumonia (PCP) is a disease affecting immunocompromised patients. PCP among these patients is associated with significant morbidity and mortality.. To assess the effectiveness of PCP prophylaxis among non-HIV immunocompromised patients; and to define the type of immunocompromised patient for whom evidence suggests a benefit for PCP prophylaxis.. Electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE and EMBASE (to March 2014), LILACS (to March 2014), relevant conference proceedings; and references of identified trials.. Randomised controlled trials (RCTs) or quasi-RCTs comparing prophylaxis with an antibiotic effective against PCP versus placebo, no intervention, or antibiotic(s) with no activity against PCP; and trials comparing different antibiotics effective against PCP among immunocompromised non-HIV patients. We only included trials in which Pneumocystis infections were available as an outcome.. Two review authors independently assessed risk of bias in each trial and extracted data from the included trials. We contacted authors of the included trials to obtain missing data. The primary outcome was documented PCP infections. Risk ratios (RR) with 95% confidence intervals (CI) were estimated and pooled using the random-effects model.. Thirteen trials performed between the years 1974 and 2008 were included, involving 1412 patients. Four trials included 520 children with acute lymphoblastic leukemia and the remaining trials included adults with acute leukemia, solid organ transplantation or autologous bone marrow transplantation. Compared to no treatment or treatment with fluoroquinolones (inactive against Pneumocystis), there was an 85% reduction in the occurrence of PCP in patients receiving prophylaxis with trimethoprim/sulfamethoxazole, RR of 0.15 (95% CI 0.04 to 0.62; 10 trials, 1000 patients). The evidence was graded as moderate due to possible risk of bias. PCP-related mortality was also significantly reduced, RR of 0.17 (95% CI 0.03 to 0.94; nine trials, 886 patients) (low quality of evidence due to possible risk of bias and imprecision), but in trials comparing PCP prophylaxis against placebo or no treatment there was no significant effect on all-cause mortality (low quality of evidence due to imprecision). Occurrence of leukopenia or neutropenia and their duration were not reported consistently. No significant differences in overall adverse events or events requiring discontinuation were seen comparing trimethoprim/sulfamethoxazole to no treatment or placebo (four trials, 470 patients, moderate quality evidence). No differences between once daily versus thrice weekly trimethoprim/sulfamethoxazole were seen (two trials, 207 patients).. Given an event rate of 6.2% in the control groups of the included trials, prophylaxis for PCP using trimethoprim/sulfamethoxazole is highly effective among non-HIV immunocompromised patients, with a number needed to treat to prevent PCP of 19 patients (95% CI 17 to 42). Prophylaxis should be considered for patients with a similar baseline risk of PCP.

Topics: Adult; Anti-Infective Agents; Child; HIV Seronegativity; Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii infection (PJP) is a common cause of pneumonia in patients with cancer-related immunosuppression. There are well-defined patients who are at risk of PJP due to the status of their underlying malignancy, treatment-related immunosuppression and/or concomitant use of corticosteroids. Prophylaxis is highly effective and should be given to all patients at moderate to high risk of PJP. Trimethoprim-sulfamethoxazole is the drug of choice for prophylaxis and treatment, although several alternative agents are available.

Topics: Adrenal Cortex Hormones; Antibiotic Prophylaxis; Consensus; Drug Administration Schedule; Humans; Immunocompromised Host; Neoplasms; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PJP) is a severe and life-threatening complication in immunocompromised patients. Trimethoprim/sulfamethoxazole (TMP-SMZ) is well known for its effectiveness as prophylaxis of PJP. However, the use of TMP-SMZ is associated with various adverse effects that may not be tolerated by critically ill patients. Caspofungin is recommended for invasive fungal infections, but the treatment of PJP after solid organ transplantation (SOT) is an off-label use of this drug. In this study, three cases of severe PJP in renal transplant recipients treated with a combination of caspofungin and low-dose TMP-SMZ were presented. Initial findings indicated that the combined treatment may be beneficial for the treatment of PJP and decrease the incidence of TMP-SMZ-related adverse effects.

Topics: Adult; Caspofungin; Drug Therapy, Combination; Echinocandins; Humans; Kidney Transplantation; Lipopeptides; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Despite the dramatic decrease in opportunistic infections after the introduction of highly active antiretroviral therapy, Pneumocystis jirovecii pneumonia remains the major AIDS related infection in France.. The clinical, radiological and microbiological diagnosis is usually easily made in HIV-infected patients. The preferred treatment is high dose trimethoprim-sulfamethoxazole, in association with steroids in cases of severe hypoxaemia. This has led to a dramatic reduction in mortality in these patients. Prophylactic treatment is mandatory in highly immunosuppressed patients (CD4 counts<200/μL) whose viraemia is not well controlled by antiretroviral therapy.. Whether PCR-based diagnosis would be useful for HIV-infected patients is a matter of debate, as is also the clinical significance of P. jirovecii colonization. The best alternative regimens for treating P. jirovecii pneumonia in cases of treatment failure or severe intolerance to trimethoprim-sulfamethoxazole are not clearly defined.. In the context of universal HIV testing and recent guideline recommendations to start antiretroviral therapy early in the course of HIV infection, the frequency of P. jirovecii pneumonia should continue to decline in France.

Topics: AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; France; HIV; HIV Infections; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Accompanying the increased use of biologic and non-biologic antirheumatic agents, patients with RA have been exposed to an increased risk of Pneumocystis jirovecii infection, which causes acute fulminant P. jirovecii pneumonia (PCP). Mortality in this population is higher than in HIV-infected individuals. Several guidelines and recommendations for HIV-infected individuals are available; however, such guidelines for RA patients remain less clear. Between 2006 and 2008 we encountered a clustering event of P. jirovecii infection among RA outpatients. Through our experience with this outbreak and a review of the recent medical literature regarding asymptomatic colonization and its clinical significance, transmission modes of infection and prophylaxis of PCP, we have learned the following lessons: PCP outbreaks among RA patients can occur through person-to-person transmission in outpatient facilities; asymptomatic carriers serve as reservoirs and sources of infection; and short-term prophylaxis for eradication of P. jirovecii is effective in controlling PCP outbreaks among RA outpatients.

Topics: Anti-Infective Agents; Arthritis, Rheumatoid; Contact Tracing; Disease Reservoirs; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Infectious Disease Transmission, Professional-to-Patient; Kidney Transplantation; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Complications; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci is an important pathogen in patients undergoing SOT and HSCT. Universal prophylaxis is recommended for all adults and children with SOT and HSCT, considering that its use significantly reduces the occurrence and mortality associated with pneumonia by this agent. The drug of choice is cotrimoxazole (A1) three times a week, low-dose scheme, that has proved equally effective and better tolerated than the daily regimen and/or at high doses. Prophylaxis starts 7 to 14 days post transplant in SOT recipients and post-implant in HSCT, with an average duration of 6 months except in liver and lung transplant as in HSCT with significant degree of immunosuppression, that lasts for 1 year. Alternatives for prophylaxis are dapsone (B2), aerosolized pentamidine (B2) and atovaquone (C2).

Topics: Adult; Anti-Infective Agents; Child; Dapsone; Drug Administration Schedule; Evidence-Based Medicine; Humans; Incidence; Organ Transplantation; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Complications; Practice Guidelines as Topic; Risk Factors; Stem Cell Transplantation; Trimethoprim, Sulfamethoxazole Drug Combination

During the past 30 years, major advances have been made in our understanding of HIV/AIDS and Pneumocystis pneumonia (PCP), but significant gaps remain. Pneumocystis is classified as a fungus and is host-species specific, but an understanding of its reservoir, mode of transmission, and pathogenesis is incomplete. PCP remains a frequent AIDS-defining diagnosis and is a frequent opportunistic pneumonia in the United States and in Europe, but comparable epidemiologic data from other areas of the world that are burdened with HIV/AIDS are limited. Pneumocystis cannot be cultured, and bronchoscopy with bronchoalveolar lavage is the gold standard procedure to diagnose PCP, but noninvasive diagnostic tests and biomarkers show promise that must be validated. Trimethoprim-sulfamethoxazole is the recommended first-line treatment and prophylaxis regimen, but putative trimethoprim-sulfamethoxazole drug resistance is an emerging concern. The International HIV-associated Opportunistic Pneumonias (IHOP) study was established to address these knowledge gaps. This review describes recent advances in the pathogenesis, epidemiology, diagnosis, and management of HIV-associated PCP and ongoing areas of clinical and translational research that are part of the IHOP study and the Longitudinal Studies of HIV-associated Lung Infections and Complications (Lung HIV).

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Anti-Infective Agents; beta-Glucans; Biomarkers; Bronchoalveolar Lavage; Bronchoscopy; CD4 Lymphocyte Count; Dihydropteroate Synthase; Drug Resistance, Fungal; HIV Infections; Humans; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Pneumothorax; Polymerase Chain Reaction; Primary Prevention; Radiography, Thoracic; S-Adenosylmethionine; Secondary Prevention; Tetrahydrofolate Dehydrogenase; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Bronchoalveolar Lavage Fluid; Caspofungin; Diagnosis, Differential; Echinocandins; Humans; Lipopeptides; Lung; Opportunistic Infections; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Severe combined immunodeficiency (SCID) is a heterogeneous group of congenital diseases characterized by their presentation with life threatening infections in the first months of life. The clinical presentation and the therapeutic outcome is influenced by multiple factors: the genetic defect, infectious complications, the presence of maternal T cells the development of Omenn syndrome, as well as non-immunological signs and symptoms of the disease. Hematopoietic stem cell transplantation (HSCT) to date is the only established curative option and allows long-term cure of the disease. Therapeutic objectives of HSCT in SCID clearly differ from those in malignant or hematological disease. Disease specific aspects and their influence on the therapeutic strategy in SCID will be discussed in this review.

Topics: Anti-Infective Agents; Donor Selection; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infant, Newborn; Opportunistic Infections; Patient Isolation; Pneumocystis carinii; Pneumonia, Pneumocystis; Prognosis; Severe Combined Immunodeficiency; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in immunocompromised renal transplant recipients. In recent years, PCP outbreaks in renal transplant centers have been reported in many countries. Person-to-person transmission between PCP patients and other recipients lacking prophylaxis is one of the possible sources of infection. To prevent infection, effective prophylaxis in susceptible patients is recommended. Trimethoprim-sulfamethoxazole (TMP-SMX) is the most effective drug for PCP prophylaxis, but its recommended duration of use after transplantation varies among the different guidelines. The European Renal Association recommends a prophylaxis period of 4 months after transplantation, the American Society of Transplantation (AST) 6-12 months, and the Kidney Disease Improving Global Outcomes guidelines 3-6 months. Lifelong prophylaxis with TMP-SMX is not recommended in renal transplant recipients; however, in many cases, PCP has occurred after the recommended prophylaxis periods after transplantation. In this minireview, we discuss the risk factors including environmental-nosocomial exposure; state-of-the-art diagnosis, treatment, prophylaxis and isolation; and references to the AST 2009 guidelines with the aim of integrating our experience with PCP outbreaks into recent reports, and we discuss how renal transplant recipients can be protected from PCP.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Cross Infection; Humans; Immunocompromised Host; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Complications; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis (Pc) jirovecii causes severe interstitial pneumonia in patients with immunodeficiency, in whom this fungus adheres with type-I alveolar epithelial cells. Therefore, it is important to perform quick diagnosis and treatment for Pc pneumonia (PcP). In general, a combination of two antifolate agents, sulfamethoxazole (inhibition of dihydropteroate synthase (DHPS)) and trimethoprim (inhibition of dihydrofolate reductase), is the first choice for PcP treatment, and pentamidine or atovaquone (inhibition of cytochrome b) are the alternative reagents for the therapy. Amino acid substitutions of drug-binding sites in DHPS shown in genotypic analysis have been reported to be associated with failures of prophylaxis / treatment or severe mortality for PcP, while there is another article showing a negative relationship between the DHPS mutations and poor prognosis. Drug sensitivity tests using the phenotypes as well as genotypes are necessary, although it is difficult to culture Pc. This review focuses on the relationship between mutations of drug-targeting molecules and treatment failure based on original data and other reports. In addition, trials of phenotypic analyses for Pc are described as promising investigations.

Topics: Adult; Aged; Atovaquone; Dihydropteroate Synthase; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Mutation; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this study was to clarify the potential advantages of a low-dose regimen of trimethoprim-sulfamethoxazole prophylaxis to prevent Pneumocystis jirovecii pneumonia (PJP) in transplant recipients (80/400 mg/d every day or 160/800 mg/d every other day) with those obtained from the full-dose prophylaxis (160/800 mg/d every day) or no prophylaxis.. Prospectively randomized and retrospectively case controlled studies were selected.. Four studies matched the inclusion criteria-2 randomized and 2 case controls-for a total of 570 patients. The pneumonia incidence was 0% after full-dose prophylaxis (0/181), 1% after the low-dose regimen (1/105), and 11% with no prophylaxis (31/284). Pneumonia occurrences were significant lower between the full-dose prophylaxis versus the no prophylaxis group (0% vs 11%; P < .001), and between the low-dose and no prophylaxis groups (1% vs 11%; P < .001). There was no difference between patients receiving the full-dose prophylaxis versus the low-dose regimen (0% vs 1%; P = NS).. The low-dose gives similar results as the full-dose regimen for the prevention of PJP and seems a feasible, safe option for transplanted patients.

Topics: Anti-Infective Agents; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Caspofungin; Echinocandins; Humans; Leukemia, Myelomonocytic, Chronic; Lipopeptides; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Uremia

Pneumocystis pneumonia (PCP) is a life-threatening infection in immunocompromised children with quantitative and qualitative defects in T lymphocytes. At risk are children with lymphoid malignancies, HIV infection, corticosteroid therapy, transplantation and primary immunodeficiency states. Diagnosis is established through direct examination or polymerase chain reaction (PCR) from respiratory secretions. Trimethoprim-sulphamethoxazole is used for initial therapy in most patients, while pentamidine, atovaquone, clindamycin plus primaquine, and dapsone plus trimethoprim are alternatives. Prophylaxis of high-risk patients reduces but does not eliminate the risk of PCP. Improved understanding of the pathogenesis of PCP is important for future advances against this life-threatening infection.

Topics: Anti-Infective Agents; Child; Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Use of cyclophosphamide in systemic lupus erythematosus (SLE) is associated with Pneumocystis jirovecii pneumonia (PJP) that has substantial morbidity and mortality. However, the frequency of PJP in these patients is unknown and there are no guidelines for prophylactic antibiotics.. The objectives of this study are to evaluate the frequency of PJP and the need for prophylactic antibiotics in these patients.. We estimated incidence of PJP and use of prophylactic trimethoprim-sulfamethoxazole in these patients by a literature search and an e-mail survey of US rheumatologists.. We identified 18 manuscripts dealing with infections in SLE patients treated with cyclophosphamide. In these manuscripts, 121 cases of PJP were identified in 76,156 SLE patients with a frequency of 15.88 per 10,000 patients.Of 264 rheumatologists surveyed, 133 (50.37%) were using prophylactic antibiotics in these patients. One hundred thirty-one (49.63%) respondents did not use prophylactic antibiotics. 5,174 SLE patients received cyclophosphamide in last 5 years with 19.6 +/- 30.6 (mean +/- SD) patients per rheumatologist. 32 cases of PJP were reported. The total cumulative experience of 264 rheumatologists was 4742 years [(17.96 +/- 10.35) (mean +/- SD)] with a PJP rate of 67.48 per 10,000 years of practice.. The frequency of PJP in SLE patients on cyclophosphamide remains low (0.1588%). Therefore, routine use of trimethoprim-sulfamethoxazole for PJP prophylaxis in SLE patients on cyclophosphamide does not appear to be substantiated by this study, except in those with elevated risk, ie, with severe leucopenia, lymphopenia, high dose corticosteroids, hypocomplementemia, active renal disease, and higher mean SLEDAI score. There is a need for consensus guidelines addressing prophylactic antibiotics in these patients.

Topics: Anti-Infective Agents; Antibiotic Prophylaxis; Antirheumatic Agents; Comorbidity; Cyclophosphamide; Health Care Surveys; Humans; Lupus Erythematosus, Systemic; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Animals; Anti-Bacterial Agents; Cryptococcosis; Cryptococcus neoformans; HIV Infections; Humans; Pneumocystis carinii; Pneumocystis Infections; Pneumonia, Pneumocystis; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is an opportunistic pathogen causing life-threatening pneumonia in immunosuppressed patients. The number of non-HIV immunosuppressed patients at risk for Pneumocystis pneumonia is rapidly growing. In contrast to HIV patients, there are no guidelines for Pneumocystis prophylaxis in other immunocompromised hosts. A detailed analysis of current literature data allowed us hereby to define the type of immunocompromised patients for whom evidence suggests a benefit for PCP prophylaxis.

Topics: Anti-Infective Agents; Connective Tissue Diseases; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; HIV Infections; Humans; Immunocompromised Host; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Protein-Energy Malnutrition; Randomized Controlled Trials as Topic; Risk Factors; Transplantation; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis

Pneumocystis pneumonia (PCP) is a common AIDS-defining opportunistic illness in people with HIV infection, but its incidence has fallen with use of prophylactic treatment. Without treatment, PCP is likely to be fatal in people with AIDS, so placebo-controlled studies would be considered unethical.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of first-line antipneumocystis treatments for Pneumocystis pneumonia in people infected with HIV? What are the effects of adjuvant corticosteroids in people receiving first-line antipneumocystis treatments for Pneumocystis pneumonia in people infected with HIV? What are the effects of treatments for Pneumocystis pneumonia in people infected with HIV who have not responded to first-line antipneumocystis treatment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 22 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: adjuvant corticosteroids, aerosolised or intravenous pentamidine, atovaquone, clindamycin-primaquone, treatment after failure of first-line treatment, trimethoprim-dapsone, and trimethoprim-sulfamethoxazole (TMP-SMX, co-trimoxazole).

Topics: Administration, Oral; Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Atovaquone; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP).. We did a systematic search of MEDLINE for all randomized and observational studies of PCP treatment published up to August 2007 and included individual treatment data of AIDS-associated PCP from a tricenter study. We calculated pooled estimates of reported outcome of second-line treatment using averaged odds ratios (ORs).. Twenty-nine studies with sufficient detail of second-line treatment and outcome, including data from 82 individual cases from the tricenter study, yielded a total of 468 PCP second-line treatment episodes. Response rates to second-line treatment were comparable for trimethoprim-sulfamethoxazole (TMP-SMX; 68%) and clindamycin-primaquine (73%) (OR for response = 2.1 [95% confidence interval (CI): 1.1 to 3.2] and 2.7 [95% CI: 1.3 to 4.0], respectively) but were considerably lower for intravenous pentamidine (44%; OR = 0.8 [95% CI: 0.6 to 1.0]).. Clindamycin-primaquine is an alternative to intravenous pentamidine as second-line treatment for PCP in patients who fail treatment with TMP-SMX. TMP-SMX should be used as a second-line treatment for those failing first-line treatments with regimens other than TMP-SMX.

Topics: AIDS-Related Opportunistic Infections; Clindamycin; Cohort Studies; Humans; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Primaquine; Salvage Therapy; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Inflammatory Agents; Antiprotozoal Agents; Biopsy; Bronchoscopy; CD4 Lymphocyte Count; Clindamycin; Dapsone; Developing Countries; Drug Therapy, Combination; Global Health; Humans; Oxygen Inhalation Therapy; Patient Selection; Pentamidine; Pneumonia, Pneumocystis; Prednisone; Primaquine; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is a disease affecting immunocompromised patients. PCP among these patients is associated with significant morbidity and mortality.. To assess the effectiveness of PCP prophylaxis among non-HIV immunocompromised patients. To define the type of immunocompromised patients for whom evidence suggests a benefit for PCP prophylaxis.. Electronic searches of The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 1, 2007), PubMed (March 2007), LILACS (March 2007), relevant conference proceedings; references of identified trials; the first author of each included trial was contacted.. RCTs or quasi- RCTs comparing prophylaxis with an antibiotic effective against Pneumocystis versus placebo, no intervention, an antibiotic/s with no activity against Pneumocystis or another antibiotic effective against Pneumocystis for immune-compromised non-HIV patients. Only trials pre-defining Pneumocystis infections as an outcome were included.. Two authors independently appraised the quality of each trial and extracted data from included trials. Relative risks (RR), with 95% confidence intervals (CI) were estimated and pooled using the random effects model.. Eleven trials including 1155 patients (520 children), performed between the years 1974 and 1997, were included. Compared to no treatment or treatment with fluoroquinolones (inactive against Pneumocystis), there was a 91% reduction in the occurrence of PCP in patients receiving prophylaxis with trimethoprim/sulfamethoxazole, RR 0.09 (95% CI 0.02 to 0.32), eight trials, 821 patients. No significant difference was encountered in all cause mortality, RR 0.81 (95% CI 0.27 to 2.37), five trials, 509 patients, while PCP-related mortality was significantly reduced, RR 0.17 (95% CI 0.03 to 0.94), seven trials, 701 patients. Occurrence of leukopenia, neutropenia and their duration were not reported consistently. No significant difference in any adverse event was seen comparing trimethoprim/sulfamethoxazole to no treatment/ placebo (four trials, 470 patients). No differences between once daily versus thrice weekly trimethoprim/sulfamethoxazole were seen (two trials, 207 patients).. Given an event rate of 7.5% as in included trials' control group, prophylaxis for PCP using TMP/SMX is highly effective among non-HIV patients, with a number needed to treat of 15 patients (95% CI 13 to 20). Prophylaxis should be considered for the types of patients with hematological malignancies, bone marrow transplantation and solid organ transplantation included in these trials.

Topics: Adult; Anti-Infective Agents; Child; Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the efficacy of prophylaxis for Pneumocystis pneumonia (PCP), caused by Pneumocystis jirovecii (formerly Pneumocystis carinii), for immunocompromised non-HIV-infected patients by conducting a systematic review and meta-analysis.. We searched for randomized controlled trials that compared prophylaxis using antibiotics effective against P jirovecii, given orally or intravenously, vs placebo, no intervention, or antibiotics with no activity against P jirovecii. In addition, we included trials that compared different PCP prophylactic regimens or administration schedules. The search included the Cochrane Central Register of Controlled Trials, PubMed, Latin American and Caribbean Health Sciences Literature, and conference proceedings. No language, year, or publication restrictions were applied. Two reviewers (H.G. and M.P.) independently searched, selected trials, extracted data, and performed methodological quality assessment. Relative risks (RRs) with 95% confidence intervals (CIs) are reported. Meta-analysis was performed using the random-effects model.. Twelve randomized trials were identified, including 1245 patients (50% children) who had undergone autologous bone marrow or solid organ transplant or who had hematologic cancer. When trimethoprim-sulfamethoxazole was administered, a 91% reduction was observed in the occurrence of PCP (RR, 0.09; 95% CI, 0.02-0.32); the number needed to treat was 15 (95% CI, 13-20) patients, with no heterogeneity. Pneumocystis pneumonia-related mortality was significantly reduced (RR, 0.17; 95% CI, 0.03-0.94), whereas all-cause mortality did not differ significantly (RR, 0.79; 95% CI, 0.18-3.46). Adverse events that required discontinuation occurred in 3.1% of adults and none of the children, and all were reversible. No differences between once-daily and thrice-weekly administration schedules were found.. Balanced against severe adverse events, PCP prophylaxis is warranted when the risk for PCP is higher than 3.5% for adults. Adverse events are less frequent in children, for whom prophylaxis might be warranted at lower PCP incidence rates.

Topics: Anti-Infective Agents; Antibiotic Prophylaxis; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Bacterial infection is a major cause of morbidity and mortality among patients with HIV living in Africa. Broadening the scope of cotrimoxazole (CTX) prophylaxis to cover patients whose CD4 counts are above 200 cells/mm(3) has been suggested as a means of improving the control of infectious disease on the continent. CTX has demonstrated antimalarial benefit in Central and West Africa, but in areas of high bacterial resistance to CTX, the prophylactic role of CTX as an antibacterial agent is less clear. In particular there is little to suggest that prophylactic CTX provides reliable control against the pneumococcus. In both South Africa and the Gambia, several clinical studies with pneumococcal conjugate vaccines have resulted in improved clinical outcomes for children with and without HIV infection. There is clearly much more that needs to be done, and conjugate vaccines provide a unique opportunity to improve the future lives of Africa's children.

Topics: Adolescent; Adult; Africa South of the Sahara; Anti-Infective Agents; Bacterial Infections; Child; HIV Infections; Humans; Infant, Newborn; Pneumococcal Vaccines; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

We report a case of dual Mycobacterium tuberculosis (TB) and Pneumocystis jiroveci (carinii) (PCP) lymphadenitis in a patient with HIV who had been receiving trimethoprim-sulfamethoxazole (TMP-SMX) as systemic prophylaxis for PCP. This patient was successfully treated with antituberculosis medications and TMP-SMX. Our review of the literature identified this as the first reported case of dual TB and PCP lymphadenitis in an HIV-infected host and highlights the potential limitations of TMP-SMX prophylaxis.

Topics: Adult; Antibiotic Prophylaxis; Female; HIV Infections; Humans; Lymphadenitis; Mycobacterium tuberculosis; Pneumocystis carinii; Pneumocystis Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Lymph Node

We report a case of rhabdomyolysis associated with the use of trimethoprim-sulfamethoxazole (TMP-SMX) in a newly diagnosed AIDS patient with presumed Pneumocystis jiroveci (formerly named Pneumocystis Carinii) pneumonia. The present case is significant because of the paucity of similar cases in the literature and the relative frequency with which TMP-SMX is used today.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Male; Pneumonia, Pneumocystis; Rhabdomyolysis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Antiprotozoal Agents; Atovaquone; Clindamycin; Dapsone; Drug Therapy, Combination; HIV Infections; Humans; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci (P. jiroveci) is the etiological agent of pneumocystis pneumonia (PCP) in immunodeficient patients. The increased interest of clinicians in this particular pathogen during the past decade was prompted by rising numbers of patients with immunosuppression caused by AIDS, chemotherapy, or organ transplantation. Premature, seriously ill infants at intensive care units constitute a potential risk group for infection with P. jiroveci. Recent advances in medical sciences, owing mainly to developments in molecular biology, permitted the verification of the taxonomic position of pathogens and contributed to a better understanding of new aspects of pathophysiology and pathogenesis of PCP. It has been demonstrated that the genus Pneumocystis represents a heterogeneous group of opportunistic fungi exhibiting narrow host specificity. Pneumocystis jiroveci is the species which is specific for humans. The present paper outlines the clinical symptoms of PCP in infants, currently used diagnostic methods, and treatment procedures in PCP.

Topics: Anti-Infective Agents; Antifungal Agents; Humans; Infant, Newborn; Infant, Premature, Diseases; Intensive Care, Neonatal; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pediatric heart transplantation is a surgical therapy for dilated cardiomyopathy and for complex congenital heart defects with low pulmonary artery resistance. However, it is still discussed as controversial because of uncertain long-term results. We report our experience with pediatric heart transplantation in a heterogeneous population.. Since 1988, 50 heart transplants were performed in 47 patients (30 with dilated cardiomyopathy, 17 with congenital heart disease). Mean age was 9.4 +/- 6.9 years (range, 4 days to 17.9 years). Twenty-three patients had a total of 36 previous operations. Clinical outcome was evaluated retrospectively.. Perioperative mortality was 6% due to primary graft failure. Late mortality (12%) was caused by acute rejection (n = 2), pneumonia (n = 2), intracranial hemorrhage (n = 1), and suicide (n = 1). Mean follow-up was 5.24 +/- 3.6 years. Actuarial 1, 5, and 10 year survival was 86%, 86%, and 80% and improved significantly after 1995 (92% [1 year]; 92% [5 years]). There was no significant difference between patients with dilated or congenital heart disease (1 year: 86% vs 82%; 5 years: 83% vs 74%; 10 years 83% vs 74%; p = 0.62). Three patients with therapy resistant acute or chronic rejection and assisted circulation underwent retransplantation and are alive. Freedom from acute rejection after 5 years was 40% with primary cyclosporine immunosuppression regime and 56% with tacrolimus. Since the introduction of mycophenolate mofetil, freedom from acute rejection increased to 62%. All survivors are at home and in good cardiac condition.. Pediatric heart transplantation is the treatment of choice for end-stage dilated cardiomyopathy as for congenital heart disease with excellent clinical midterm results. It is a valid alternative to reconstructive surgery in borderline patients. However, further follow-up is necessary to evaluate the long-term side effects of immunosuppressants.

Topics: Adolescent; Antiviral Agents; Bacterial Infections; Cardiomyopathy, Dilated; Child; Child, Preschool; Cyclosporine; Cytomegalovirus Infections; Extracorporeal Membrane Oxygenation; Female; Follow-Up Studies; Ganciclovir; Germany; Graft Rejection; Heart Defects, Congenital; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Immunosuppressive Agents; Life Tables; Lymphoma, Non-Hodgkin; Male; Mycophenolic Acid; Pneumonia, Pneumocystis; Postoperative Complications; Reoperation; Retrospective Studies; Survival Analysis; Survival Rate; Tacrolimus; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vascular Resistance; Virus Diseases

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Antifungal Agents; Antitubercular Agents; Antiviral Agents; Azithromycin; Chickenpox; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Ganciclovir; Herpes Simplex; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Pneumonia, Pneumocystis; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Topics: Atovaquone; Clindamycin; Corticosterone; Dapsone; Drug Therapy, Combination; HIV Infections; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cytokines; Humans; Macrophages; Pneumocystis carinii; Pneumonia, Pneumocystis; Pulmonary Alveoli; Trimethoprim, Sulfamethoxazole Drug Combination

Infants with HIV infection are vulnerable to Pneumocystis carinii pneumonia (PCP) during their first year of life. WHO and the Joint United Nations Programme on HIV/AIDS now recommend that all children of HIV-positive mothers receive prophylactic cotrimoxazole against PCP from six weeks of age and continue this therapy until exposure through breast milk ceases-and the infant is confirmed to be HIV-negative (rarely before one year of age). Empirical prophylaxis invokes a trade-off between possible benefit to the infant versus the risk of resistance to antibiotics and antimalarials. From a critical analysis of the literature, we offer a conceptual model demonstrating how, under certain circumstances, a policy of mass cotrimoxazole prophylaxis may be counterproductive.

Topics: Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Breast Feeding; Chemoprevention; Drug Resistance; Humans; Infant; Infant, Newborn; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

A case of Pneumocystis carinii pneumonia in a patient without an underlying immunosuppressing condition is reported, and 12 other previously reported cases are reviewed. When compared with Pneumocystis carinii pneumonia in association with AIDS and in other immunosuppressing conditions, Pneumocystis carinii pneumonia in patients without predisposing conditions resembles more closely that seen in immunosuppressing conditions other than AIDS.

Topics: Follow-Up Studies; Humans; Immunocompetence; Infusions, Intravenous; Male; Middle Aged; Pneumonia, Pneumocystis; Risk Assessment; Severity of Illness Index; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Drug Therapy, Combination; HIV Infections; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii is an opportunistic eukaryotic pathogen most common causing pneumonia in immunocompromised host. DNA P. carinii f. sp. hominis has been frequently detected in air samples collected from environments of P. carinii pneumonia (PCP) patients and nasal swabs samples from contact health care workers and family. Epidemiological studies suggested not-only the possibility of person-to-person infection transmission. First hypothesis of reactivation latent infection of the causing the new episode of PCP based on serological studies. Recently findings based molecular studies has suggested new acquired infection may to be cause of many cases of PCP. Early diagnosis, therapy and effective prophylaxis of PCP is a very important strategy to reduce morbidity and mortality among infected patients. The combination of trimethoprim (TMP) and sulfamethoxazole (SMX) is effective for prophylaxis and treatment P. carinii pneumonia. Empiric therapy in immunocompromised host also including AIDS patients with anti-Pneumocystis prophylaxis is also not recommended. Both dapsone and sulfamethoxazole act inhibiting the folate biosynthetic enzyme DHPS. Mutations identified in P. carinii in gene coding this enzyme are associated with resistance to sulfonamide. P. carinii may also developing resistance to atovaquone, second-line therapeutic and prophylactic agent.

Topics: Anti-Infective Agents; Antifungal Agents; Atovaquone; Drug Resistance, Multiple, Fungal; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia is a major cause of illness and death in immunocompromised hosts. The numbers of pneumocystis pneumonia cases in Thailand have increased each year from 1992 to 2000 and peaked in 2000 at 6,255 cases. The microbe that causes pneumocystis pneumonia in humans is called Pneumocystis jirovecii. Pneumocystis sp. was discovered nearly a century ago, but the knowledge of Pneumocystis sp. remained poorly understood, until the molecular biology techniques help scientists verify it fungus nature. In the past, Pneumocystis sp. was misclassified as protozoan due to its morphologic features. Later, it was reclassified as fungus due to DNA analysis. Cotrimaxazole, the combination of trimethoprim-sulfamethoxazole, is the drug of choice for treatment and prophylaxis of pneumocystis pneumonia. However, increasing evidence of mutations in the enzyme dihydropteroate synthase (DHPS), the target of sulfa drugs represent emergence of sulfa resistance.

Topics: Animals; Anti-Infective Agents; Drug Resistance, Microbial; Genotype; Humans; Life Cycle Stages; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Bronchoalveolar Lavage Fluid; Humans; Immunocompromised Host; Intermittent Positive-Pressure Ventilation; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Chickenpox; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Ganciclovir; Herpes Simplex; Humans; Mycobacterium avium-intracellulare Infection; Naphthoquinones; Pneumonia, Pneumocystis; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Herpes Simplex; Herpes Zoster; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Naphthoquinones; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Topics: Anti-Infective Agents; Connective Tissue Diseases; Drug Therapy, Combination; Humans; Molecular Diagnostic Techniques; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) is still the commonest AIDS-defining condition in the UK, although absolute numbers have fallen since 1990 with the advent of prophylaxis and highly active antiretroviral therapy (HAART). Further decreases in its incidence are unlikely unless efforts are made to reduce late first presentations of HIV, improve retention of patients in care and improve adherence to P. carinii prophylaxis. The widespread development of key mutations in the P. carinii dihydropteroate synthase gene in the 1990's suggests that the organism is evolving under positive evolutionary pressure, possibly mediated by widespread use of co-trimoxazole and dapsone prophylaxis. It is not clear whether these mutants lead to treatment failure with co-trimoxazole, since most episodes are treated successfully and failure of prophylaxis is rare. Molecular diagnosis of PCP is restricted to research use, due to difficulties with sensitivity, specificity and turn-around times. Patients are infected with multiple P. carinii subtypes and re-infection from an environmental source is probably more important than re-activation of an existing infection. Person-to-person transmission does not appear to be a major source of infection in HIV-infected patients. Recent reports have highlighted the potential complications of initiating HAART during treatment of PCP.

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Antiretroviral Therapy, Highly Active; Drug Resistance, Fungal; HIV Infections; Humans; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A 45-year-old man underwent renal transplant for end-stage renal disease complicating systemic lupus erythematosis. Within 24 hours of initiating Pneumocystis carinii pneumonia (PCP) prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) he developed fever and confusion. Cerebrospinal fluid examination revealed a pleocytosis but cultures were negative. The patient improved within three days after cessation of the TMP-SMX but symptoms recurred rapidly upon drug rechallenge. Drug-induced aseptic meningitis is an uncommon but well described clinical entity. This is the first case described in a patient following renal transplantation. The literature is reviewed and the clinical features, diagnostic challenges and possible mechanisms of TMP-SMX-induced aseptic meningitis are discussed. This problem may be more common in the transplant population than is recognized given the difficulty of diagnosis combined with the widespread use of TMP-SMX as PCP prophylaxis.

Topics: Anti-Infective Agents; Humans; Kidney Transplantation; Male; Meningitis, Aseptic; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the relative efficacies of alternative antipneumocystis agents in human immunodeficiency virus (HIV)-infected patients with Pneumocystis carinii pneumonia unresponsive to primary drug treatment with a combination product of trimethoprim and sulfamethoxazole or parenteral pentamidine.. Meta-analysis of 27 published clinical drug trials, case series, and case reports involving P carinii pneumonia. Data extracted included underlying disease, primary antipneumocystis treatment, days of failed primary treatment, salvage regimen, use of systemic corticosteroids and antiretroviral drugs, and clinical outcome.. In 497 patients with microbiologically confirmed P carinii pneumonia (456 with HIV or acquired immunodeficiency syndrome), initial antipneumocystis treatment failed and they therefore required alternative drug therapy. Failed regimens included trimethoprim-sulfamethoxazole (160 patients), intravenous pentamidine (63 patients), trimethoprim-sulfamethoxazole and/or pentamidine (258 patients), aerosolized pentamidine (6 patients), atovaquone (3 patients), dapsone (3 patients), a combination product of trimethoprim and dapsone (2 patients), and trimethoprim-sulfamethoxazole followed by a combination of clindamycin and primaquine phosphate (2 patients). Efficacies of salvage regimens were as follows: clindamycin-primaquine (42 to 44 [88%-92%] of 48 patients; P<10(-8)), atovaquone (4 [80%] of 5), eflornithine hydrochloride (40 [57%] of 70; P<.01), trimethoprim-sulfamethoxazole (27 [53%] of 51; P<.08), pentamidine (64 [39%] of 164), and trimetrexate (47 [30%] of 159).. The combination of clindamycin plus primaquine appears to be the most effective alternative treatment for patients with P carinii pneumonia who are unresponsive to conventional antipneumocystis agents.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Child; Child, Preschool; Clindamycin; Drug Therapy, Combination; Eflornithine; Female; Humans; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Salvage Therapy; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

A 70-year-old man treated for 6 months with prednisolone for nephrotic syndrome, was referred to our pulmonary division because of a nodule in the right lower lung field. Nocardia asteroides was isolated from the culture of the percutaneous lung aspiration, and the case was diagnosed as pulmonary nocardiosis. The lesion disappeared after 2 months of therapy with sulfamethoxazole/trimethoprim (1,600 mg/320 mg once a day). Though it had been given prophylactically (800 mg/160 mg twice a week) for the prevention of pneumocystis carinii pneumonitis.

Topics: Aged; Humans; Male; Nephrotic Syndrome; Nocardia asteroides; Nocardia Infections; Opportunistic Infections; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonitis (PCP) is one of the most important opportunistic infections in children and adolescents with cancer. Its high frequency and a considerable mortality have led to primary chemoprophylaxis in patients with hematological malignancies and following allogeneic hematopoietic stem cell transplantation. Although less well characterized, patients with autologous stem cell transplantation and patients with dose-intensive chemotherapy for pediatric solid tumors may have a similarly high risk for PCP based on their profound T-cell depletion. For more than two decades, effective chemoprophylaxis for PCP has been available. Trimethoprim and sulfamethoxazole (TMP/SMX) is the prophylactic modality of first choice. The combination has been shown to be almost 100 % efficacious in pediatric cancer patients at highest risk, and it is usually well tolerated in this setting. Secondary alternatives to TMP/SMX include oral dapsone, oral atovaquone, and aerosolized pentamidine-isethionate. These modalities are less effective than TMP/SMX, and have been evaluated predominantly in HIV-infected patients. This article reviews epidemiology and current approaches to chemoprophylaxis for PCP in children and adolescents with cancer and/or hematopoietic stem cell transplantation, and provides evidence-based guidelines for indications and modalities of PCP prophylaxis in this population.

Topics: Adolescent; Age Factors; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Atovaquone; Child; Child, Preschool; Dapsone; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Naphthoquinones; Neoplasms; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chemoprevention; Child; Child, Preschool; HIV Infections; Humans; Infant; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; CD4 Lymphocyte Count; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Inflammatory Agents; Diagnosis, Differential; Drug Therapy, Combination; Humans; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Prednisolone; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination

Antiinfective drugs may show the same mechanisms of nephrotoxicity as other drugs, and these can be subgrouped into vascular, tubulotoxic, tubulo-obstructive, and immunologic effects. While vascular effects of antiinfective drugs are rare, tubulotoxicity is a well known phenomenon, especially in connection with aminoglycosides and amphotericin B as well as cephalosporins, pentamidine, foscarnet, and cidovir. The tubulo-obstructive effect caused by precipitation of the drug and first observed after treatment with sulfonamides in the 1940s, has become a renascent problem now that high doses of sulfonamides are being given to immunocompromised patients (sulfadiazine, cotrimoxazole). Moreover, this effect has also been associated with newer antiviral drugs like acyclovir and indinavir. We describe a transplant patient who received high doses of cotrimoxazole for pneumocystis carinii pneumonia and lost transplant function mainly due to bioptically proven glomerular and tubular crystallization with tubular degeneration caused by sulfamethoxazole. Acute interstitial nephritis is the main immunologic effect of antiinfective drugs (especially rifampicin but also cephalosporins, quinolones, sulfonamides, and penicillins). Immune stimulation by cytokine treatment (mainly interferon-alpha) involves several kinds of autoimmune renal diseases like acute interstitial nephritis or glomerulonephritis as well as interstitial and vascular rejection of renal transplants.

Topics: Adult; Anti-Infective Agents; Autoimmune Diseases; Female; Glomerulonephritis; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Transplantation; Kidney Tubules; Nephritis, Interstitial; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Animals; Antibiotic Prophylaxis; Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Fungal Vaccines; Humans; Microbial Sensitivity Tests; Naphthoquinones; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Pyrimethamine; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/Sulfamethoxazole is the most effective medication used in both the treatment and prevention of Pneumocystis carinii pneumonia (PCP) in patients with HIV/AIDS. Its use, however, is accompanied by a high incidence of adverse reactions, especially fever, myalgia and rash (sulfa hypersensitivity). In a group of our patients, we have examined the clinical parameters at the time of onset of sulfa hypersensitivity, and the success of a desensitization protocol for this adverse event. We also have performed a comprehensive review of the literature on sulfa hypersensitivity and have compared our results to those previously reported in the literature. Our findings indicate that the sulfa hypersensitivity reaction is more likely to develop in patients with advanced disease and that desensitization can restore tolerability to the drug in approximately two thirds of those who attempt it.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Atovaquone; Clindamycin; Dapsone; Eflornithine; Humans; Macrolides; Naphthoquinones; Pentamidine; Pneumocystis; Pneumocystis Infections; Pneumonia, Pneumocystis; Pyrimidines; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

A patient with the acquired immunodeficiency syndrome (AIDS) and sickle cell anemia presented to the University of Wisconsin Hospital on two separate occasions with pneumocystis carinii pneumonia (PCP). On both occasions he was treated with high-dose intravenous trimethoprim/sulfamethoxazole (TMP/SMX). Several days into each treatment course he developed hyperkalemia and systemic acidosis consistent with hyperkalemic renal tubular acidosis (RTA). The abnormalities resolved in the first instance with the addition of amphotericin B while continuing TMP/SMX, and in the second upon discontinuation of the TMP/SMX. While an increasing number of cases with TMP/SMX-induced hyperkalemia have been reported, hyperkalemic RTA is an uncommon complication of TMP/SMX therapy, occurring in patients with predisposing factors for acidosis such as aldosterone defects, medullary dysfunction and renal insufficiency.

Topics: Acidosis, Renal Tubular; Adult; AIDS-Related Opportunistic Infections; Anemia, Sickle Cell; Anti-Infective Agents; Drug Therapy, Combination; HIV-1; Humans; Hyperkalemia; Male; Pneumonia, Pneumocystis; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) is one of the leading complications among HIV-infected patients. Recent advances in PCP prophylaxis, diagnosis and treatment have caused a decrease in PCP-related morbidity and mortality. Despite these advances, PCP continues to be frequent in patients not known to be HIV-infected and in those patients with poor adherence to prophylactic regimens or severe immunosuppression. In typical cases diagnosis may be suspected by the patient's clinical presentation. Clinicians are frequently faced with the differential diagnosis between PCP, bacterial pneumonia, pulmonary tuberculosis, and other specific respiratory disorders HIV-associated. Definitive diagnosis of PCP requires demonstration of Pneumocystis carinii (PC) in respiratory secretions or lung tissue. Conventional techniques, immunofluorescence using monoclonal antibodies and molecular techniques are highly specific, but sensitivity varies depending on the PC load present in the sample. Best diagnostic yield is obtained analyzing samples obtained by bronchoalveolar lavage. PC diagnosis using highly sensitive PCR in sputum-induced samples might allow noninvasive diagnosis in most HIV-infected patients suffering from PCP but PCR techniques remain to be standardized. Like in PCP prophylaxis, trimethoprim-sulphametoxazole (TS) is the drug of choice for PCP treatment. In severe case, TS is given intravenously. If patient is intolerant to TS, i.v. pentamidine or i.v. trimetrexate with folinic acid can be used. TS has a dose-dependent toxicity. In cases of hypersensitivity to TS, drug-desensitization should be tried. In severe documented PCP adjunctive corticosteroid therapy is effective and safe. In mild to moderate PCP, TS can be given orally. Best alternatives to TS in this situation are dapsone-pyrimethamine or clindamycin-primaquine (CP). Other effective options are oral atovaquone, aerosolize pentamidine and i.v. pentamidine.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Diagnosis, Differential; DNA, Bacterial; Humans; Pneumocystis; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Early effective management of Pneumocystis carinii pneumonia improves outcome in patients with this disorder. Trimethoprim-sulfamethoxazole remains the agent of choice for treatment of severe P. carinii pneumonia. Pentamidine, trimethoprim-dapsone, atovaquone, and other regimens are useful in selected clinical situations. Adjunctive corticosteroids are indicated in patients with acquired immune deficiency syndrome and P. carinii pneumonia who have moderate to severe P. carinii pneumonia defined as a room air arterial PaO2 less than 70 mm Hg or an alveolar-arterial oxygen gradient of greater than 35 mm Hg. The use of trimethoprim-sulfamethoxazole, dapsone, and aerosolized pentamidine in immunocompromised patients without AIDS is also reviewed.

Topics: Adrenal Cortex Hormones; Anti-Infective Agents; Antifungal Agents; Atovaquone; Clinical Trials as Topic; Dapsone; Female; Humans; Male; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Since the end of the 1980s, primary anti-Pneumocystis carinii pneumonia (PCP) prophylaxis has become a fundamental part of the global AIDS control strategy in industrialized countries. The widespread adoption of anti-PCP chemoprophylaxis has been a key element in prolonging the survival of patients with AIDS. There is general agreement on the need to begin chemoprophylaxis when individual CD4+ cell counts drop below the value of 200/microL. However, PCP still develops in up to 27% of susceptible HIV-infected patients despite regular prophylaxis intake. Failure of chemoprophylaxis may depend on different factors. The choice of the regimen and the patient's compliance to it have been the first variables to be identified, whereas the importance of the residual cellular immune function as complementary protective mechanism against PCP has emerged in subsequent clinical studies. Albeit of limited general concern, issues such as P. carinii drug resistance and defective drug absorption may play some role in prophylaxis failure in selected patients. Regarding the epidemiology of primary and recurrent episodes of PCP, recent studies based on genetic fingerprinting techniques revealed that interhuman transmission of the organism could be more relevant than so far expected, thus raising some concern of the possibility of nosocomial spread among susceptible individuals. The downgrading tendency of immune competence in HIV infection and the related increasing risk of developing PCP make it possible to envisage a two-step chemoprophylactic strategy, with the most effective compound, cotrimoxazole, to be reserved for the last and most risky disease stage, when immune response no longer provides any support for preventing the development of PCP.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Male; Patient Compliance; Pneumonia, Pneumocystis; Prevalence; Prognosis; Survival Rate; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

A report is made here of five patients who underwent solid organ transplantation, were not infected with the human immunodeficiency virus, and suffered Pneumocystis carinii pneumonia while receiving immunosuppressive drugs. The figure represents a prevalence of 0.43% among patients with solid organ transplantation at the Clínica Puerta de Hierro. Some features of this infection are reported in patients without AIDS, both transplanted patients and with other clinical conditions, the possible predisposing factors and the necessity to keep a high suspect index when individuals treated with immunosuppressive drugs present with respiratory symptoms. Likewise, a suggestion is made to consider the use of chemoprophylaxis with cotrimoxazole in these cases.

Topics: Adult; Aged; Anti-Infective Agents; Drug Therapy, Combination; Fatal Outcome; Female; Ganciclovir; Humans; Immunosuppression Therapy; Male; Middle Aged; Opportunistic Infections; Organ Transplantation; Pneumonia, Pneumocystis; Postoperative Complications; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole remains the treatment of choice in patients with Pneumocystis carinii pneumonia (PCP) requiring intravenous therapy. Those patients who require intravenous therapy who cannot tolerate or who fall therapy with trimethoprim-sulfamethoxazole may be treated with either pentamidine or trimetrexate (plus folinic acid), with or without orally administered dapsone. The toxicity of the former drug makes trimetrexate-based therapy the preferred second choice for parenteral use. Treatment with trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine is approximately of equivalent efficacy, but variable toxicity, in patients with mild to moderate PCP for whom an oral route of administration is appropriate. Atovaquone, formulated as an oral suspension, is also effective, but, in the absence of additional data, must be considered as second line therapy. Adjunctive corticosteroid therapy is indicated for patients with [PAO2-PaO2] more than 30 mm Hg or PaO2 less than 70 mm Hg [corrected] while breathing ambient air in the absence of contraindications. Recognition of the apparent fungal nature of P carinii as well as improved understanding of the pathophysiology of PCP will lead to further improvements in antipneumocystis therapy.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Humans; Infusions, Intravenous; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

In a meta-analysis, we examined the efficacy of aerosolized pentamidine, trimethoprim-sulfamethoxazole, and dapsone or dapsone/pyrimethamine for the prevention of Pneumocystis carinii pneumonia and toxoplasma encephalitis in patients with HIV infection. Of 22 trials, 13 compared trimethoprim-sulfamethoxazole with aerosolized pentamidine, nine compared dapsone alone or in combination with pyrimethamine with aerosolized pentamidine, and eight compared trimethoprim-sulfamethoxazole with dapsone/pyrimethamine. In total, 1484 patients were treated with trimethoprim-sulfamethoxazole, 1548 patients with dapsone/pyrimethamine or dapsone, and 1800 patients with aerosolized pentamidine. For dapsone/pyrimethamine versus aerosolized pentamidine, the risk ratio for P. carinii pneumonia was 0.90 (95% confidence interval [CI], 0.71-1.15), and for toxoplasma encephalitis it was 0.72 (95% CI, 0.54-0.97). For trimethoprim-sulfamethoxazole versus aerosolized pentamidine, the risk ratio of P. carinii pneumonia was 0.59 (95% CI, 0.45-0.76), and for toxoplasma encephalitis it was 0.78 (95% CI, 0.55-1.11). For trimethoprim-sulfamethoxazole versus dapsone/pyrimethamine, the risk ratio of P. carinii pneumonia was 0.49 (95% CI, 0.26-0.92), and for toxoplasma encephalitis it was 1.17 (95% CI, 0.68-2.04). Although current evidence does not allow a definitive recommendation, administration of trimethoprim-sulfamethoxazole for prophylaxis of P. carinii pneumonia and toxoplasmosis in patients with HIV infection is consistent with the available data.

Topics: Administration, Inhalation; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Dapsone; Encephalitis; HIV Infections; Humans; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Randomized Controlled Trials as Topic; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Cortex Hormones; Adult; AIDS-Related Opportunistic Infections; Child; Clindamycin; Drug Therapy, Combination; Humans; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Animals; Antifungal Agents; Artemether; Artemisinins; Humans; Pneumonia, Pneumocystis; Sesquiterpenes; Trimethoprim, Sulfamethoxazole Drug Combination

Finding the optimal strategy for Pneumocystis carinii prophylaxis in patients with human immunodeficiency virus infection can be problematic. Several prophylactic regimens are available, but their relative efficacy and tolerance are not well understood.. A meta-analysis overviewed 35 randomized trials comparing different regimens for P carinii prophylaxis directly or with placebo. Analyses were based on intention-to-treat. On-treatment data were also analyzed when available.. Regardless of dose, sulfamethoxazole-trimethoprim was almost universally effective for patients who tolerated it. The risk of discontinuing sulfamethoxazole-trimethoprim because of side effects decreased by 43% (95% confidence interval, 30% to 54%) if one double-strength tablet was given three times a week instead of daily. For dapsone, among 100 patients given 100 mg daily instead of twice a week for 1 year (primary prophylaxis), seven fewer patients would develop P carinii pneumonia, but 17 more would have significant toxic reactions. Aerosolized pentamidine was well tolerated regardless of the dose used. Prophylaxis failures might be halved if the dose of aerosolized pentamidine were doubled. Compared with aerosolized pentamidine, oral regimens prevented 73% (95% confidence interval, 57% to 82%) of toxoplasmosis events by on-treatment analysis, but only 33% (95% confidence interval, 12% to 50%) by intention-to-treat. No significant difference in mortality was demonstrated between different regimens.. Sulfamethoxazole-trimethoprim is the superior regimen, and low doses could improve tolerance without losing effectiveness for primary prophylaxis. Low doses of dapsone reduce toxic effects, but at the expense of some loss of efficacy. There are few data on the use of low-dose regimens for secondary prophylaxis. High doses of aerosolized pentamidine may improve the efficacy of this regimen. Aerosolized pentamidine is inadequate for prevention of toxoplasmosis, and strategies that improve the tolerance of oral regimens may increase effectiveness in preventing toxoplasmosis.

Topics: AIDS-Related Opportunistic Infections; Dapsone; Dose-Response Relationship, Drug; Humans; Logistic Models; Multivariate Analysis; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Survival Analysis; Toxoplasmosis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The increased resistance, intolerance, or allergy to trimethoprim/sulfamethoxazole (TMP/SMX) has brought much attention to alternative treatment of pneumonia caused by Pneumocystis carinii (PCP). Pentamidine is considered when there is documented allergy or intolerance to TMP/SMX. Similarly, either dapsone/trimethoprim or clindamycin/primaquine is effective in the treatment of mild to moderate PCP, but both regimens are contraindicated in glucose 6-phosphate dehydrogenase (G6PD) deficiency. For this purpose, atovaquone should be used in patients who are deficient in G6PD or who are unable to be on TMP/SMX or pentamidine. On the other hand, in severe disease, adjunctive corticosteroids can enhance the efficacy of either TMP/SMX or pentamidine. If these therapies yield no response, trimetrexate with leucovorin has been approved as initial and salvage therapy in severe PCP. We review alternative treatment to TMP/SMX and propose ideal and practical therapeutic and prophylactic guidelines in the treatment and prevention of PCP.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Drug Combinations; Drug Hypersensitivity; Drug Resistance, Microbial; Humans; Leucovorin; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Adverse cutaneous reactions frequently occur during the treatment of AIDS associated pneumocystosis by trimethoprime-sulfamethoxazole. The most common form is a maculous rash. Treating throughout the duration of hypersensitivity may lead to potentially lethal Stevens-Johnson and Lyell syndromes. Slow acetylator phenotype, a glutathion deficiency and a history of adverse cutaneous reactions have been identified as risk factors of cutaneous reactions. An adjuvant corticosteroid therapy decreases the frequency of adverse cutaneous reactions during the treatment of hypoxaemic pneumocystosis by trimethoprim-sulfamethoxazole.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Eruptions; Humans; Incidence; Pneumonia, Pneumocystis; Risk Factors; Stevens-Johnson Syndrome; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aerosols; Child; Dapsone; Humans; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Trimethoprim, Sulfamethoxazole Drug Combination

Low-dose weekly pulse MTX therapy is effective for rheumatoid arthritis (RA) and is used for patients with RA who are unresponsive to conventional disease-modifying antirheumatic drugs (DMARDs). We used MTX to a 62-year-old man with RA who had received DMARDs for 5 years. MTX was effective for RA but after 12 weeks MTX therapy started, he complicated pancytopenia and developed Pneumocystis carinii pneumonia. We reviewed all RA patients reported in Japan and in the world from 1965, complicated with Pancytopenia (37 cases) and Pneumocystis carinii pneumonia (13 cases) after MTX therapy. Results were as following; (1) MTX should not be used with TMP-SMX. and risk factors for pancytopenia were (2) age over 60 years old (3) renal hypofunction (4) use of NSAID.

Topics: Age Factors; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Contraindications; Humans; Kidney Diseases; Male; Methotrexate; Middle Aged; Pancytopenia; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Incidence; Pneumonia, Pneumocystis; Primary Prevention; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Use of methotrexate to treat rheumatoid arthritis is associated with pulmonary adverse effects in 3% to 5% of cases. In addition to immunoallergic lung disease, bronchitis and pneumonia due to pyogenic organisms, opportunistic lower respiratory tract infections have been reported, including, to our knowledge, 18 cases of Pneumocystis carinii pneumonia. We report two new cases of P. carinii pneumonia in methotrexate-treated rheumatoid arthritis patients. One case occurred in a 62-year-old woman with a nine-year history of seropositive rheumatoid arthritis treated for the last seven months with methotrexate, 15 mg per week, and prednisone, 10 mg/d. The other patient was a 58-year-old woman who had been diagnosed with rheumatoid arthritis 18 months earlier and had been receiving 15 mg per week of methotrexate for eight months in combination with 12.5 mg of prednisone per day. Both patients had negative tests for the human immunodeficiency virus. Symptoms consisted of fever, cough and dyspnea, with interstitial infiltrates on chest films, hypoxia, and lymphopenia (700 and 600/mm3, respectively). The diagnosis was confirmed by bronchoalveolar lavage. Both patients recovered under treatment with trimethoprim-sulfamethoxazole. An analysis of the 20 cases of P. carinii pneumonia reported to date in methotrexate-treated rheumatoid arthritis patients demonstrated a number of characteristics: the rheumatoid arthritis was of recent onset in some cases (a few months in one patient); lymphopenia was present in two thirds of cases; one-third of patients were not receiving corticosteroid therapy; the dosage and duration of methotrexate therapy varied widely, from 5 to 30 mg per week and two to 48 months; and four patients died.

Topics: Anti-Infective Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Bronchoalveolar Lavage; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Methotrexate; Middle Aged; Pneumonia, Pneumocystis; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

Although alternative therapy for PCP remains limited, the role of TMP/SMX desensitization becomes increasingly important in patients with AIDS. Various successful desensitization protocols have been described in this article. As there are no established guidelines, it appears that the desensitization procedure can occur in small successive doses given each day or one small dose given daily. An evaluation of the severity of allergic reaction can be used to determine the type of dosing regimen. We believe that protocols starting with low doses and slow titration to full-dose therapy, as used at our institution, should be efficacious. Monitoring of the patient after the desensitization procedure should continue, as sensitivity may reoccur. In addition, while the patient is undergoing desensitization, some investigators recommend that alternative therapy be continued until full-dose TMP/SMX therapy is achieved. Also, it is important to realize that once a patient is successfully desensitized, medication compliance must be maintained because, theoretically, reexposure to the drug after a lapse in therapy may result in hypersensitivity reactions. Therefore, this procedure and the possibility of serious adverse effects, such as Stevens-Johnson syndrome and anaphylaxis, should be evaluated carefully and discussed thoroughly with each patient prior to initiation of therapy. Finally, a study of sufficient size should be performed to evaluate the efficacy of desensitization regimens and establish specific dosing guidelines.

Topics: Anti-Infective Agents; Desensitization, Immunologic; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Follow-Up Studies; Humans; Male; Pneumonia, Pneumocystis; Tremor; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole is a frequently prescribed antibiotic with a wide spectrum of antimicrobial activity. As a result of the increasing number of AIDS patients requiring therapy for Pneumocystis carinii pneumonia, high dose trimethoprim-sulfamethoxazole use had dramatically increased. A previously unreported and potentially lethal adverse reaction associated with high dose trimethoprim-sulfamethoxazole therapy, hyperkalemia, subsequently developed. Recognition of this potassium disorder led to investigation and description of the mechanism by which trimethoprim-sulfamethoxazole induced hyperkalemia. Trimethoprim was found to act like the potassium-sparing diuretic amiloride and reduce renal potassium excretion. Subsequent to this work, a handful of cases noted the development of hyperkalemia with standard dose trimethoprim-sulfamethoxazole in elderly patients without evidence of an obvious defect in potassium homeostasis. A prospective surveillance study of patients treated with standard dose trimethoprim-sulfamethoxazole as compared to similar controls treated with other antibiotics confirmed the rise in potassium concentration associated with trimethoprim-sulfamethoxazole therapy. Patients with mild renal insufficiency were the only group at significant risk for more severe hyperkalemia. Hence, trimethoprim-sulfamethoxazole therapy can be complicated by hyperkalemia regardless of the dose employed.

Topics: Age Factors; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Dose-Response Relationship, Drug; Humans; Hyperkalemia; Kidney; Pneumonia, Pneumocystis; Potassium; Renal Insufficiency; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Thanks to a simplification of surgical techniques, single or double lung transplants have expanded significantly in latter years. Infection remains an important cause for morbidity and mortality, more so in early rather than late stages. Bacterial infections cause approximately fifty per cent of all infections. They can be prevented in part by prophylaxis. Infections to CMV have become less frequent thanks to adequate prophylaxis with ganciclovir. Herpetic infections are prevented by acyclovir or ganciclovir. A better control of immunosuppression seems to be associated with fewer lymphoproliferative disorders secondary to the Epstein-Barr virus. Respiratory viruses remain a serious threat for these patients, although infections due to respiratory syncitial virus may be attenuated by ribavirine. Fungal infections are dangerous but prophylactic prescription of azole derivatives have reduced the incidence and severity. Prophylaxis of infections to Pneumocystis carinii is essential, the use of sulfamethoxazole trimethoprim is efficacious against this as well as nocardiosis. Infections to Mycobacterium tuberculosis are often atypical and should be looked for and anticipated whenever possible.

Topics: Acyclovir; Antibiotic Prophylaxis; Antifungal Agents; Antiviral Agents; Bacterial Infections; Chemoprevention; Cytomegalovirus Infections; Ganciclovir; Graft Survival; Heart-Lung Transplantation; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immunosuppression Therapy; Lung Transplantation; Lymphoproliferative Disorders; Mycobacterium Infections, Nontuberculous; Nocardia Infections; Pneumonia, Pneumocystis; Respiratory Syncytial Virus Infections; Ribavirin; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Tumor Virus Infections; Virus Diseases

Pneumocystis is typically described in the immunodepressed. We report a case of pneumocystis occurring in a patient without known depression of the immune system. The patient, aged 50, was hospitalised for a diffused infiltration pneumonia which developed sub-acutely, and presented with increasing dyspnoea of effort, thoracic pain and a disturbances of general health. The initial assessment did not reveal any risk factors for HIV infection nor any past history of note. The diagnosis of pneumocystis was confirmed by the presence of Pneumocystis carinii in the bronchoalveolar lavage from two samples. There was a favourable outcome following the prescription of Cotrimoxazole for three months and steroid therapy. HIV serology was negative and the sub-population of lymphocytes was normal. A search for neoplasia or systematic disease remained negative.

Topics: Adrenal Cortex Hormones; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Chest Pain; Diagnosis, Differential; Dyspnea; Humans; Male; Middle Aged; Pneumocystis; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumonia is an important cause of morbidity and mortality in the United States. The provision of effective prophylaxis for pneumonia has become a major goal for both public health officials and individual physicians. Prophylaxis for community-acquired pneumonia is pathogen-specific and is directed toward the most common microorganisms that cause it. The 23-valent pneumococcal polysaccharide vaccine; the trivalent influenza vaccine; the Haemophilus b conjugate vaccine; and either trimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine are recommended to prevent Streptococcus pneumoniae, influenza viruses, H. influenzae type b, and Pneumocystis carinii respectively. Except for the microorganisms listed above, the prevention of nosocomial pneumonia is not pathogen-specific. Rather, prevention of nosocomial pneumonia requires the use of infection control procedures, including patient and staff education; isolation of patients with highly contagious respiratory pathogens; vigorous hand washing; cleaning and sterilizaton of respiratory equipment; and use of sterile water in nebulizers and humidifiers. It also requires procedures to limit pooling and aspiration of secretions, such as positioning and rotation of the bed-bound patient; frequent suctioning of respiratory secretions using gloves and sterile suction catheters; and limiting enteral alimentation. Finally, selective decontamination of the digestive tract may be considered for intubated patients.

Topics: Anti-Bacterial Agents; Antifungal Agents; Bacterial Vaccines; Community-Acquired Infections; Cross Infection; Dapsone; Equipment Contamination; Haemophilus Vaccines; Hand Disinfection; Humans; Infection Control; Influenza Vaccines; Intubation, Intratracheal; Patient Education as Topic; Patient Isolation; Pentamidine; Personnel, Hospital; Pneumonia; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Pneumonia, Pneumocystis; Pneumonia, Viral; Public Health; Sterilization; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Evidence from the literature strongly supports that high doses of TMP, as used in the treatment of PCP in AIDS patients, have the propensity to cause hyperkalemia by inhibiting sodium channels in the distal nephron, thereby impairing potassium secretion. The mechanism of TMP-induced hyperkalemia is believed to be similar to that of triamterene and amiloride because of the structural similarity of these agents. It is also possible that declining renal function, which is a natural progression of HIV disease, may contribute to the hyperkalemia seen in this patient population. In addition, patients with AIDS also may exhibit a defect in adrenal function, potentiating the hyperkalemic effect of TMP therapy. Therefore, it is crucial for clinicians to monitor closely the serum potassium concentration in this patient population, especially during therapy with high doses of TMP.

Topics: Acquired Immunodeficiency Syndrome; Clinical Trials as Topic; Dapsone; Drug Therapy, Combination; Humans; Hyperkalemia; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The transmission, diagnosis, and clinical manifestations of human immunodeficiency virus (HIV) infection in children up to 13 years of age are reviewed, and maintenance and prophylactic drug therapies for these patients are discussed. HIV can be transmitted from mother to infant in utero, during delivery, or through breast milk. Perinatal transmission accounts for almost 90% of all pediatric HIV infections. HIV infection can be diagnosed with HIV culturing, polymerase chain reaction testing, the enzyme-linked immunosorbent assay, the Western blot antibody assay, or the p24 core-antigen assay. Testing should begin as soon as possible after the at-risk child reaches one month of age. CD4+ lymphocyte counts are also used in diagnosis and monitoring. The median age at diagnosis of AIDS in children with perinatally acquired HIV infection is 12-24 months. Among the many possible clinical features are Pneumocystis carinii pneumonia (PCP), cytomegalovirus infection, failure to thrive, encephalopathy, recurrent bacterial infection, thrush, lymphoid interstitial pneumonitis, lymphadenopathy, pancreatis, hepatitis, anemia, and thrombocytopenia. Zidovudine is considered the drug of choice for initial therapy in HIV-infected children and is indicated for asymptomatic infection, early symptomatic disease, and advanced disease. However, new research is questioning the role of zidovudine monotherapy. Didanosine is the only agent with FDA-approved labeling for use as second-line therapy in children who do not respond to or become resistant to zidovudine. Agents under investigation for pediatric use are zalcitabine, stavudine, lamivudine, and nevirapine. Drug combinations, such as zidovudine plus didanosine, are also being examined. Zidovudine appears to reduce the rate of maternal transmission of HIV. Agents used prophylactically against PCP in children are trimethoprim-sulfamethoxazole, dapsone, and inhaled or i.v. pentamidine. HIV-infected children should also received prophylaxis against recurrent bacterial infections. The standard pediatric immunization schedule is used, but inactivated injectable poliovirus vaccine must be given instead of the live oral vaccine. Zidovudine remains the first-line agent for treating HIV infection in children. Alternatives are available for those who do not respond to zidovudine.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Child; Child, Preschool; Dapsone; Didanosine; Drug Interactions; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Pregnancy; Pregnancy Complications, Infectious; Recurrence; Stavudine; Trimethoprim, Sulfamethoxazole Drug Combination; Zalcitabine; Zidovudine

At the start of the AIDS epidemic, the only agents licensed for treatment of Pneumocystis carinii pneumonia (PCP) were trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine. Both are effective against PCP, but their use has been compromised by adverse reactions that necessitate discontinuing therapy in < or = 54% of patients. As a result of the limitations in the use of these therapies, research efforts have been directed toward the development of effective agents with an improved safety profile. Of these agents, one of the best studied is atovaquone, a hydroxynaphthoquinone that has been licensed by the U.S. Food and Drug Administration for use in the treatment of mild to moderate PCP in patients intolerant to TMP-SMX. Clinical studies have shown that atovaquone is associated with overall therapeutic success rates equivalent to those of intravenous pentamidine and TMP-SMX, although its therapeutic efficacy rates are somewhat lower. However, atovaquone is associated with fewer treatment-limiting side effects than the other drugs. The literature concerning the efficacy and safety of atovaquone for the treatment of PCP will be reviewed.

Topics: AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Antiprotozoal Agents; Atovaquone; Cohort Studies; Humans; Male; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Rats; Tablets; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Quality of Health Care; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; CD4 Lymphocyte Count; Child, Preschool; Female; Humans; Infant; Infectious Disease Transmission, Vertical; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Quality of Health Care; Trimethoprim, Sulfamethoxazole Drug Combination

Although the incidence of Pneumocystis carinii pneumonia (PCP) among adults infected with human immunodeficiency virus (HIV) has declined, no decline in PCP incidence has been observed among HIV-infected children, and PCP remains the most common serious opportunistic infection among both adults and children in the United States. Some evidence of airborne transmission of P. carinii exists, and some clusters of cases of PCP have been reported; however, data are insufficient to recommend that persons with PCP be separated from immunosuppressed persons as a standard practice. The incidence of PCP can be reduced substantially if persons at risk for PCP are identified and receive adequate chemoprophylaxis. Several drugs and drug combinations are highly effective in preventing PCP. For both adults and children, oral trimethoprim-sulfamethoxazole (TMP-SMZ) is the preferred form of prophylaxis. Adverse effects are commonly associated with the use of TMP-SMZ and in some cases may necessitate withdrawal of the drug until the effects resolve. However, reintroduction at the same dose or at a lower and gradually increasing dose will often permit the continued use of TMP-SMZ. For persons intolerant of TMP-SMZ, dapsone alone and dapsone plus pyrimethamine are effective alternatives. A third alternative is aerosolized pentamidine. Additional drugs of unproven efficacy but of potential use in exceptional cases are available.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Child; Dapsone; Drug Therapy, Combination; Humans; Incidence; Infection Control; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Research; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Atovaquone; Clindamycin; Clinical Trials as Topic; Dapsone; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cytomegalovirus Retinitis; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The treatment and the prevention of Pneumocystis carinii pneumonia (PCP) is based on trimethoprim-sulfamethoxazole. However, hypersensitivity reactions occur often in HIV-infected patients. In this study, clinical and biological parameters of 27 PCP-patients treated by this drug association were analyzed. We divided the drug reactions into two groups according to the severity. A drug reaction occurred in 59.2% of the patients and was note as a mild reaction in 18.5% of the cases and as a severe reaction in 40.7%. An initial high eosinophil count was noted in patients who may present future drug reaction. This difference was more significant in patients who may present severe drug reaction. No other clinical or biological factors were predictive of hypersensitivity. The immune status of HIV-disease, drug therapy, and drug mechanisms were discussed.

Topics: Adult; AIDS-Related Opportunistic Infections; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Predictive Value of Tests; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole is an important medication for the treatment and prevention of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Use of this medication has been limited by the high frequency of adverse reactions that occur in patients with human immunodeficiency virus disease. This article reviews the incidence and spectrum of adverse reactions and options for continuing therapy with trimethoprim-sulfamethoxazole in human immunodeficiency virus-infected patients who have adverse reactions.

Topics: AIDS-Related Opportunistic Infections; Drug Hypersensitivity; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Drug Eruptions; HIV Infections; Humans; Pneumonia, Pneumocystis; Sulfanilamides; Trimethoprim, Sulfamethoxazole Drug Combination

Intolerance to sulfonamides is very frequent in HIV-infected subjects and 10 times more common than in the general population. There are 2 types of intolerance to sulfonamides: early reactions with urticaria or angioedema, which are IgE-dependent, and late reactions with febrile rash, which occur between the 6th and 12th days of treatment and represent the vast majority of allergic manifestations in HIV-infected subjects. Clinically, these reactions resemble serum sickness, but all physiopathological hypotheses point to toxic process. The degradation of sulfonamides has two different pathways: the N-acetylation pathway which is genetically determined and saturable, and the cytochrome P450 pathway which produces toxic hydroxylamine metabolites "detoxified" by glutathione. In HIV-infected subjects detoxication is thought to be incomplete due to an acquired deficiency of glutathione and probably increased in the presence of a slow acetylation profile.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Drug Eruptions; Humans; Pneumonia, Pneumocystis; Sulfadiazine; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Ganciclovir; Humans; Immunocompromised Host; Mycoses; Pneumonia; Pneumonia, Pneumocystis; Pneumonia, Viral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Clinical Trials as Topic; HIV Infections; Humans; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumonia caused by Pneumocystis carinii is the most frequent indication for admission of AIDS patients to intensive care units. In this article, an approach to the diagnosis and management of this condition will be presented along with prognostic information. Differential diagnosis will be discussed, and characteristic responses to current standard and alternative chemotherapeutic agents and modes of ventilatory support will be reviewed.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Diagnosis, Differential; Health Personnel; Humans; Infection Control; Intensive Care Units; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Respiration, Artificial; Respiratory Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acyclovir; Combined Modality Therapy; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Humans; Immunization, Passive; Liver Transplantation; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Pneumonia, Viral; Trimethoprim, Sulfamethoxazole Drug Combination

The armamentarium of drugs to treat and to prevent Pneumocystis pneumonia has expanded substantially over the past decade. In all patient populations trimethoprim-sulfamethoxazole is the preferred regimen for both acute treatment and prophylaxis. Clindamycin-primaquine and atovaquone are both effective agents for acute therapy but there are no data yet suggesting that they are preferable to trimethoprim-sulfamethoxazole. Corticosteroid therapy is now standard for severe AIDS-associated Pneumocystis pneumonia, and should probably be used in other patient populations with severe pneumocystis pneumonia as well.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Clindamycin; Clinical Trials as Topic; Drug Tolerance; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Following the initial observation by Dr. Margaret Fischl that trimethoprim-sulfamethoxazole can prevent Pneumocystis carinii infection in patients with Kaposi's sarcoma, initiating prophylaxis for pneumocystic infection in all patients with less than 200 CD4+ cells/mm3 has become accepted practice. This prophylactic intervention has been found not only to reduce the development of pneumonia due to P. carinii but also to prolong life. Drs. Henry Masur and Joseph A. Kovacs first reviewed prophylaxis for P. carinii pneumonia in patients infected with the human immunodeficiency virus for the AIDS Commentary 3 years ago. They have updated that initial review for this AIDS Commentary, placing currently available information into concise clinical perspective and detailing a rational plan for the clinician to follow based on results of recent studies.

Topics: Administration, Inhalation; Aerosols; CD4-Positive T-Lymphocytes; HIV Infections; Humans; Leukocyte Count; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

To review published abstracts, case reports, and journal articles and evaluate data examining the use of systemic corticosteroids as adjuvant treatment for Pneumocystis carinii pneumonia (PCP) in patients with AIDS.. Computerized online databases, peer-reviewed journals from January 1986 through September 1991, and personal communication with a National Institutes of Health correspondent.. The authors identified 13 reports pertinent to this review. By author consensus, five studies were selected for analysis based on sample size, controlled study design, and clinical outcome measures. Recommendations of an expert panel from the National Institutes of Health and the University of California also are discussed.. Data are presented based on the methodologic strength of the studies reviewed. Studies are assessed on sample size, inclusion criteria, comparative cohort populations, specific patient outcome measures, and statistical analysis.. Results of the study analysis support the use of systemic corticosteroids as early adjunctive therapy for AIDS patients with moderate-to-severe PCP who have an initial arterial oxygen partial pressure of less than 70 mm Hg or an alveolar-arterial gradient greater than 35 mm Hg on room air. Improved outcomes included decreased mortality, respiratory failure, and deterioration of oxygenation. Data evaluated have shown that adjuvant corticosteroid therapy is most effective when initiated within 72 hours of beginning specific antipneumocystis therapy. A small, but sometimes significant, increased rate of infection in steroid-treated patients was noted.. Based on the literature reviewed, early systemic adjuvant corticosteroid therapy can benefit patients with moderate-to-severe AIDS-related PCP. The steroid regimen used in the largest controlled trial and recommended by the expert panel is prednisone 40 mg bid (days 1-5), then 40 mg/d (days 6-10), then 20 mg/d (days 1-21).

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Humans; Methylprednisolone; Pentamidine; Pneumonia, Pneumocystis; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) emerged in the 1980s as the most common opportunistic infection among patients with the acquired immunodeficiency syndrome (AIDS). Because of this, the presentation and clinical course of PCP has become well-known to many physicians. However, PCP continues to occur among patients not infected with the human immunodeficiency virus, generally those who receive immunosuppressive therapy as treatment for neoplastic disease. A review from Memorial Sloan-Kettering Cancer has shown that a new group of patients, those receiving corticosteroid therapy for brain neoplasm, are also at risk for the development of PCP and should receive PCP prophylaxis. Previously defined patient groups--people with acute lymphocytic leukemia or allogeneic bone marrow transplantation--also should continue to receive prophylaxis. In addition, the clinical course and outcome of patients with neoplastic disease who develop PCP may differ from those with AIDS and PCP: the disease may be much more fulminant among patients with neoplastic disease, and the mortality rate much higher, approaching 50% in the Memorial Sloan-Kettering Cancer Center series. Wider use of prophylaxis should decrease the frequency of this disease, whereas prompt initiation of therapy in patients with a compatible syndrome should help to improve mortality rates.

Topics: Humans; Immunocompromised Host; Immunosuppression Therapy; Neoplasms; Pneumonia, Pneumocystis; Prognosis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Humans; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The primary objective of this article is to introduce readers to the use of a new agent, trimetrexate (TMTX), in the treatment of Pneumocystis carinii pneumonia (PCP). The article also gives the readers an overview of PCP and discusses some of the controversies surrounding it. Pharmacokinetic data and clinical trials are reviewed, as well as adverse effects, drug interactions, and dosage guidelines.. A MEDLINE search was used to identify pertinent literature, including reviews.. As both pharmacokinetic and clinical trials were few in number, all available trials were reviewed.. Pharmacokinetic data from trials involving patients with AIDS was sparse; therefore, those involving oncology patients, including a pediatric population, were included. Although more trials need to be done in AIDS patients, the results from the oncologic trials give us a baseline from which to extrapolate. All clinical trials available at the time of publication were reviewed as were all of the preliminary results from three ongoing trials, which were made available through a personal communication.. TMTX has been found to be 1500 times more potent than trimethoprim as a dihydrofolate reductase inhibitor, and has the potential to provide an effective therapeutic option for PCP. TMTX is a lipid-soluble analog of methotrexate and is thus capable of greater penetration into Pneumocystis cells, which lack the folate membrane transport system necessary to take up classic folate structures like leucovorin and methotrexate, thereby negating any clinical effectiveness of methotrexate and allowing leucovorin to be used for host cell rescue. TMTX's pharmacokinetic parameters best fit a multicompartmental model with a terminal half-life of up to 12 hours. It is cleared both hepatically and renally with up to 41 percent excreted unchanged in the urine. Although TMTX's pharmacokinetic parameters are variable, the need for plasma concentration monitoring at present is unclear, as no dose-response relationship has been established.

Topics: Acquired Immunodeficiency Syndrome; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Topics: Acquired Immunodeficiency Syndrome; Drug Therapy, Combination; Foscarnet; Ganciclovir; Humans; Male; Opportunistic Infections; Pentamidine; Phosphonoacetic Acid; Pneumonia, Pneumocystis; Sulfadiazine; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) is the most frequently occurring opportunistic infection in individuals infected with the human immunodeficiency virus. Improved methods of diagnosing and treating PCP have resulted in increased survival rates. Nurses are more frequently faced with treatment of the critical care patient with PCP. Knowledge about the mechanisms and manifestations of PCP as well as its diagnosis and treatment provides a baseline for the nursing management of PCP. Nursing care for the critically ill adult patient with PCP focuses on the management of the human responses to PCP including hyperthermia, impaired gas exchange, altered respiratory function, fatigue, and altered nutrition, and on the management of the side effects of treatment including nausea, vomiting, and hypoglycemia. Effective interventions related to these patient problems can improve the quality of care and ultimately affect patient outcomes.

Topics: Acquired Immunodeficiency Syndrome; Humans; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination

The clinical features of three patients with a life-threatening reaction to trimethoprim-sulfamethoxazole (TMP-SMZ) are presented along with seven other cases from the literature. All patients developed sudden fever and hypotension immediately after the administration of TMP-SMZ; usually this reaction occurred within approximately 2 weeks of completion of a previous course of the drug. All but one patient had a rash. Most patients were hypoxemic and developed diffuse pulmonary infiltrates. All patients responded rapidly to supportive care, while bacterial cultures remained negative. The presence, absence, or character of previous adverse reactions to TMP-SMZ did not predict subsequent severe reactions. Although its mechanism remains unclear, this reaction has features of both IgE-mediated anaphylaxis and cytokine (tumor necrosis factor)-mediated effects. We advise extreme caution, with close observation, when this drug is first readministered to patients who have experienced any TMP-SMZ-associated toxicity within the previous 6-8 weeks.

Topics: Adult; Diarrhea; Dyspnea; Fever; HIV Infections; Humans; Hypotension; Hypoxia; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Acquired Immunodeficiency Syndrome; Aerosols; Animals; Cryptococcosis; Cytomegalovirus Infections; Dapsone; Drug Combinations; Humans; Mycobacterium avium-intracellulare Infection; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Sulfadoxine; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

The diagnosis of Pneumocystis carinii pneumonia (PCP) rests on the isolation of this micro-organism in patients whose latest blood count, less than 2 months old, shows less than 250 CD4 lymphocytes per cubic mm and who present with signs of impaired lung function. Bronchoalveolar lavage (BAL) is the reference diagnostic method, but induced expectoration may be the initial examination, in which case BAL is performed only when the latter fails or gives negative results. Prognostic factors are those of any interstitial pneumonia plus those specific to PCP and those associated with HIV infection. It is only when no initial severity factor is present that cure can be contemplated, provided the effectiveness of treatment is evaluated daily. Cotrimoxazole is the reference drug for comparisons with all new treatments; the indications of corticosteroid therapy and the necessity of intensive care techniques are now better determined. The frequency of PCP and its mortality rate should be reduced, and one may look forward to a time when this disease will be rare and atypical, thereby raising other diagnostic and therapeutic problems.

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; CD4-Positive T-Lymphocytes; Dapsone; Eflornithine; Folic Acid Antagonists; HIV Infections; Humans; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Quinazolines; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Although Pneumocystis carinii pneumonia (PCP) can occur in any patient with severe impairment of immunity, there has been a sharp rise in incidence with the spread of human immunodeficiency virus through the USA and Western Europe, where nearly 80% of patients with HIV infection have at least one episode of PCP during their lifetime (Murray et al, 1984).

Topics: Antimalarials; CD4-Positive T-Lymphocytes; Clinical Protocols; Dapsone; Drug Combinations; HIV Infections; HIV-1; Humans; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination

The origin of the increased frequency of side-effects to co-trimoxazole in HIV-positive patients is unknown. Data on plasma concentrations of the parent compounds are inconclusive. Evidence points to the hydroxylamine derivatives of sulphamethoxazole as the reactive metabolites that cause adverse reactions to co-trimoxazole. HIV-positive individuals have a systemic glutathione deficiency, and therefore a reduced capacity to scavenge such metabolites. This process would lead to an increased exposure to toxic intermediates and would explain the high frequency of adverse reactions to co-trimoxazole in these patients.

Topics: Acquired Immunodeficiency Syndrome; Glutathione; Humans; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

This review paper is divided into three parts. The first two parts are devoted to an analytical description of the clinical, diagnostic, prognostic and therapeutic aspects of the various bronchopulmonary and pleural lesions observed in AIDS. The third part presents an overall view of the main diagnostic and therapeutic approaches in the main clinical situations covering all respiratory disorders.

Topics: Acquired Immunodeficiency Syndrome; Humans; Lymphoma, Non-Hodgkin; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Respiratory Tract Infections; Sarcoma, Kaposi; Trimethoprim, Sulfamethoxazole Drug Combination

The scientific basis for using folinic acid in combination with the antiparasitic drugs prescribed to AIDS patients has been reviewed. In vitro and experimental data are unclear. On the basis of folinic acid metabolism and pharmacology and of clinical experience, we suggest that folinic acid should not be systematically added to the curative treatment of pneumocystosis with cotrimoxazole. Folinic acid may be added to prophylactic regimens using high-dose cotrimoxazole (i.e. 800 mg sulfamethoxazole twice a day) and in malnourished patients. It should be administered as soon as cytopenia occurs in the course of treatment. Concerning toxoplasmosis, the addition of folinic acid is recommended in doses of 10 to 20 mg/day in acute therapy and 5 to 10 mg/day in maintenance therapy. Dosage must be adjusted to the results of blood counts.

Topics: Acquired Immunodeficiency Syndrome; Drug Therapy, Combination; Folic Acid; Hematologic Diseases; Humans; Leucovorin; Opportunistic Infections; Pneumonia, Pneumocystis; Pyrimethamine; Sulfadiazine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Clindamycin; Diagnosis, Differential; Humans; Pneumonia, Pneumocystis; Prognosis; Pyrimethamine; Respiration, Artificial; Sulfanilamides; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Pneumocystis carinii pneumonia is a life-threatening complication of diseases and therapies associated with immunosuppression. Approximately 80 percent of patients with acquired immunodeficiency syndrome will develop pneumocystis pneumonia. Diagnosis is important, because effective therapy is available. In most cases, diagnosis can be made by sputum analysis. Bronchoalveolar lavage will yield a diagnosis in 85 to 90 percent of patients with pneumocystis pneumonia, and is used when sputum induction and analysis is unproductive, unavailable or negative. Transbronchial biopsy and, rarely, open lung biopsy will yield the etiology of pneumonia in the remaining patients. Pentamidine or trimethoprim-sulfamethoxazole is the treatment of choice. Toxicity often occurs, including hypoglycemia, nephrotoxicity, neutropenia and rash. Corticosteroids are helpful in moderate to severe disease. Mortality for the first episode of P. carinii pneumonia averages 20 percent. Prophylaxis effectively prevents and reduces the incidence of future episodes.

Topics: Biopsy; Bronchoalveolar Lavage Fluid; Bronchoscopy; Clinical Protocols; Dapsone; Decision Trees; Diagnosis, Differential; Humans; Mass Screening; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Aerosols; Humans; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Humans; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Female; HIV Infections; Humans; Infant; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Since 1981, 1200 children with acquired immunodeficiency syndrome have been reported to the Centers for Disease Control. Among these children, Pneumocystis carinii has been the leading cause of serious morbidity and mortality. This review discusses the epidemiology, diagnosis, and treatment of P. carinii.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Child; Child, Preschool; Humans; Infant; Opportunistic Infections; Pneumocystis; Pneumonia, Pneumocystis; Prognosis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Humans; Nebulizers and Vaporizers; Pentamidine; Pneumonia, Pneumocystis; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Administration, Inhalation; Animals; Half-Life; Humans; Metabolic Clearance Rate; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

At the end of the first consensus conference on anti-infectious therapy organized by the French Language Society of Infectious Pathology in May 1990 and devoted to pneumocystosis in patients with human immunodeficiency virus (HIV) infection, the consensus committee produced this paper which answers the following 4 questions: what are the indications, technical requirements, sensitivity and benefits of induced expectoration in the diagnosis of Pneumocystis carinii pneumonia? what are the initial and secondary severity factors; in which cases is transfer to an intensive care unit indicated; in which manner can treatment be modified? what is the position occupied by corticosteroid therapy in the management of pneumocystosis? when is prophylaxis of pneumocystosis indicated; what prophylactic methods are used and how to choose among them?

Topics: Acquired Immunodeficiency Syndrome; Aerosols; Clinical Protocols; Dapsone; France; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Sputum; Trimethoprim, Sulfamethoxazole Drug Combination

In summary, recent advances in our ability to diagnose, treat, and prevent recurrences of pneumocystis pneumonia have significantly improved the clinical management of this infection, especially in HIV-1-infected individuals. As current investigations allow our therapeutic armamentarium in this disease to be strengthened even further, it is likely that pneumocystis pneumonia will pose a diminishing threat to those patients currently most susceptible to this infection.

Topics: Acquired Immunodeficiency Syndrome; Antineoplastic Agents; Humans; Opportunistic Infections; Pneumonia, Pneumocystis; Quinazolines; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

The majority of patients with AIDS and Pneumocystis carinii pneumonia respond to treatment with either high-dose cotrimoxazole or IV pentamidine. Glucocorticoids have been given as 'adjuvant' therapy in those patients who fail to respond to cotrimoxazole or pentamidine. This article discusses the role of glucocorticoids therapy in the treatment of severe Pneumocystis carinii pneumonia and reviews the evidence for their efficacy.

Topics: Glucocorticoids; Humans; Injections, Intravenous; Methylprednisolone; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Cortex Hormones; Dapsone; France; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Resuscitation; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii has taken on new importance with the emergence of the human immunodeficiency virus. It is the most common life-threatening opportunistic infection in the acquired immunodeficiency syndrome and eventually develops in 80% or more of those not receiving primary prophylaxis. This review focuses on the clinical presentation, diagnosis, treatment, and prophylaxis of P carinii pneumonia in patients with human immunodeficiency virus infection.

Topics: Acquired Immunodeficiency Syndrome; Animals; Humans; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Dapsone; Drug Therapy, Combination; Humans; Pentamidine; Pneumonia, Pneumocystis; Quinazolines; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

A large number and variety of organisms can infect the lungs of persons with AIDS. An abnormal chest X-ray associated with pulmonary symptoms should trigger a vigorous search for an infectious agent. In many cases, if the patient is ambulatory, the workup can proceed on an outpatient basis. Pneumocystis carinii pneumonia is the most common infection and also one of the most readily treatable illnesses that these patients encounter. A careful and considered diagnostic approach is necessary to conserve the time and resources of both patients and healthcare providers.

Topics: Acquired Immunodeficiency Syndrome; Ambulatory Care; Cytomegalovirus Infections; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Opportunistic Infections; Pentamidine; Pneumonia; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Topics: Acquired Immunodeficiency Syndrome; Cryptococcosis; Cytomegalovirus Infections; Dapsone; Drug Combinations; Humans; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Sulfadoxine; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia is the most common life-threatening disease diagnosed in patients infected with the human immunodeficiency virus (HIV). Patients treated for their initial episode are at risk for recurrence of the disease. HIV-positive patients with low T4 lymphocyte counts are also at risk. Conventional treatment regimens with parenteral pentamidine isethionate (Pentam 300) or trimethoprim-sulfamethoxazole have a 50% to 60% incidence of serious adverse effects and a 20% to 40% rate of failure. Aerosolized pentamidine represents a promising new therapy for HIV-infected patients. Major adverse reactions have not been reported with its use. The Food and Drug Administration's (FDA's) recent approval of aerosolized pentamidine may also have a positive effect on healthcare costs by preventing episodes of P carinii pneumonia. In addition, FDA approval may result in reimbursement of patients for this new therapy by more insurance companies.

Topics: Aerosols; Amidines; Animals; Anti-Infective Agents; Child; Drug Combinations; Female; HIV Seropositivity; Humans; Mice; Pentamidine; Pneumonia, Pneumocystis; Pregnancy; Rats; Recurrence; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Post-mortem examinations were conducted in 28 patients with the acquired immune deficiency syndrome (AIDS) and biopsy-proven Pneumocystis carinii pneumonia (PCP) who had been treated with trimethoprim-sulfamethoxazole (Bactrim, intravenous infusion [Roche]) and/or pentamidine isethionate. According to the evolution of the pulmonary process, the cases were classified into three groups. Group I ("fulminant" PCP) was composed of eight patients who died during the first week of the disease. Although treatment had eradicated most of the organisms, one third of the alveolar space volume, on the average, was filled by foamy exudates characteristic of PCP. This accounted for the respiratory insufficiency and death of these patients. Group II ("nonresolving" PCP) was comprised of nine patients who died within eight days and 2 months of diagnosis. PCP was less severe than in group I, but fatal respiratory insufficiency was the result of fibroblastic organization of the intraalveolar exudates (fibrosing alveolitis). In seven of the nine patients (78%), the latter resulted from oxygen toxicity; in the remaining two patients (22%) PCP, per se, was the original stimulus for the fibrosis. Patients in group II also had a high incidence of thromboembolic pulmonary lesions. Group III ("cured" PCP) was composed of 11 patients who responded dramatically well to therapy but died months or years later of other manifestations of AIDS. In group III patients, the roentgenographic picture at diagnosis was consistently less severe than in groups I and II.

Topics: Adult; Anti-Infective Agents; Female; Humans; Lung; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Administration, Inhalation; Administration, Oral; Humans; Nebulizers and Vaporizers; Oxygen; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Quinazolines; Recurrence; Sulfadiazine; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Antiprotozoal Agents; Clinical Trials as Topic; Dapsone; Drug Combinations; Humans; Pentamidine; Pneumonia, Pneumocystis; Quinazolines; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Aerosols; Dapsone; Drug Combinations; Humans; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Recurrence; Sulfadoxine; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Bacterial Infections; Drug Combinations; Drug Utilization; Humans; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Anti-Infective Agents; Drug Combinations; Humans; Hypoglycemia; Male; Middle Aged; Multiple Myeloma; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

AIDS is a disorder that the pediatrician must consider when evaluating children with a variety of clinical conditions, including overwhelming infection with a number of parasites. This article discusses these opportunistic parasitic infections, focusing on their link with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Age Factors; Animals; Anti-Bacterial Agents; Antiprotozoal Agents; Child; Child, Preschool; Cryptosporidiosis; Drug Combinations; Female; gamma-Globulins; Homosexuality; Humans; Infant; Male; Parasitic Diseases; Pentamidine; Pneumonia, Pneumocystis; Sulfamethoxazole; Transfusion Reaction; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; United States; Zoonoses

Topics: Acquired Immunodeficiency Syndrome; Drug Combinations; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Animals; Antibodies; Antimalarials; Child; Drug Combinations; Drug Therapy, Combination; Humans; Lung; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Pyrimethamine; Radiography; Rats; Sulfadiazine; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

In children, Pneumocystis carinii pneumonias occur mainly in cases of congenital or acquired immunodeficiencies. Definitive diagnosis rests on the visualization of the parasites, ideally by broncho-alveolar lavage. If the lavage is negative and the patient deteriorates, an open lung biopsy is the next best diagnostic method. Serological methods are unreliable. Treatment with trimethoprim-sulfamethoxazole (TMP) should be instituted as early as possible: a serum level of TMP between 5 and 10 micrograms/ml should be attained. If no improvement occurs after three days, pentamidine should be substituted. Systematic chemoprophylaxis should be given to all high-risk patients.

Topics: Animals; Child; Drug Combinations; France; History, 20th Century; Humans; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Rats; Sulfadiazine; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Antibodies; Child; Drug Combinations; Humans; Immunologic Deficiency Syndromes; Lung; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Pulmonary Alveoli; Radiography; Recurrence; Risk; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Infection is the major cause of morbidity and mortality in children receiving anticancer therapy. Children who have severe neutropenia (neutrophil count less than 100/mm3) for longer than 2 weeks should receive oral antibiotic prophylaxis. At present, trimethoprim sulfamethoxazole in combination with either nystatin or amphotericin B is the best regimen for reducing the incidence of serious infections. Trimethoprim sulfamethoxazole is very effective in the prevention of Pneumocystis carinii pneumonitis. Clinicans will have to balance the advantages and disadvantages of prophylaxis in patients who are at risk for P. carinii pneumonitis.

Topics: Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Child; Compliance; Drug Combinations; Humans; Leukemia; Neoplasms; Neutropenia; Nystatin; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Antibodies, Viral; B-Lymphocytes; beta 2-Microglobulin; Biopterins; Candidiasis, Oral; Drug Combinations; Humans; Interferon Type I; Lymphocyte Activation; Neopterin; Pneumonia, Pneumocystis; Retroviridae; Sarcoma, Kaposi; Sulfamethoxazole; T-Lymphocytes, Regulatory; Thymalfasin; Thymosin; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

A phase III randomised, placebo-controlled, trial to directly compare the efficacy and safety of low-dose TMP-SMX (10 mg/kg/day of TMP) with the standard of care (15 mg/kg/day of TMP) among patients with PJP, for a composite primary outcome of change of treatment, new mechanical ventilation, or death. The trial will be undertaken at 16 Canadian hospitals. Data will be analysed as intention to treat. Primary and secondary outcomes will be compared using logistic regression adjusting for stratification and presented with 95% CI.. This study has been conditionally approved by the McGill University Health Centre; Ethics approval will be obtained from all participating centres. Results will be submitted for publication in a peer-reviewed journal.. NCT04851015.

Topics: Canada; Clinical Trials, Phase III as Topic; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) due to Pneumocystis jirovecii infection is the leading cause of fatal opportunistic infections in immunocompromised patients. We will determine whether a daily sulfamethoxazole-trimethoprim (SMX/TMP) dose of 200/40 mg was non-inferior to 400/80 mg for PCP prevention in patients with systemic rheumatic disease under immunosuppressive therapy. This is a randomized, open-label, multicenter controlled trial. The primary outcome is the rate of PCP prevention at 52 weeks. The secondary outcome is the discontinuation rate of SMX/TMP. The trial will evaluate the optimal dose of SMX/TMP for PCP prevention in patients with systemic rheumatic disease under immunosuppressive therapy.

Topics: Adult; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Female; Humans; Male; Multicenter Studies as Topic; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Sulfamethoxazole-trimethoprim (SMX/TMP) is a standard drug for the prophylaxis of Pneumocystis pneumonia (PJP) in immunosuppressed patients with systemic rheumatic diseases, but is sometimes discontinued due to adverse events (AEs). The objective of this non-blinded, randomized, 52-week non-inferiority trial was to quest an effective chemoprophylaxis regimen for PJP with a low drug discontinuation rate. Results at week 24 were reported.. Adult patients with systemic rheumatic diseases who started prednisolone ≥0.6 mg/kg/day were randomized into three dosage groups: a single-strength group (SS, SMX/TMP of 400/80 mg daily), half-strength group (HS, 200/40 mg daily), and escalation group (ES, started with 40/8 mg daily, increasing incrementally to 200/40 mg daily). The primary endpoint was non-incidence rates (non-IR) of PJP at week 24.. Of 183 patients randomly allocated at a 1:1:1 ratio into the three groups, 58 patients in SS, 59 in HS, and 55 in ES started SMX/TMP. A total of 172 patients were included in the analysis. No cases of PJP were reported up to week 24. Estimated non-IR of PJP in patients who received daily SMX/TMP of 200/40 mg, either starting at this dose or increasing incrementally, was 96.8-100% using the exact confidence interval as a post-hoc analysis. The overall discontinuation rate was significantly lower with HS compared to SS (p = 0.007). The discontinuation rates due to AEs were significantly lower with HS (p = 0.006) and ES (p = 0.004) compared to SS. The IR of AEs requiring reduction in the dose of SMX/TMP (p = 0.009) and AEs of special interest (p = 0.003) were different among the three groups with significantly higher IR in SS compared to HS and ES.. Although there were no PJP cases, the combined group of HS and ES had an excellent estimated non-IR of PJP and both were superior in safety to SS. From the perspective of feasibility and drug discontinuation rates, the daily half-strength regimen was suggested to be optimal for prophylaxis of PJP in patients with systemic rheumatic diseases.. The University Hospital Medical Information Network Clinical Trials Registry number is UMIN000007727 , registered 10 April 2012.

Topics: Adult; Aged; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Female; Humans; Immunocompromised Host; Male; Middle Aged; Pneumonia, Pneumocystis; Rheumatic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia (PJP) is the most common opportunistic infection in infants with vertically acquired HIV infection and the most common cause of death in HIV-infected infants.. To determine whether early administration of adjuvant corticosteroids in addition to standard treatment reduces mortality in infants with vertically acquired HIV and clinically diagnosed PJP when co-infection with cytomegalovirus and other pathogens cannot be excluded.. A double-blind placebo-controlled trial of adjuvant prednisolone treatment in HIV-exposed infants aged 2-6 months admitted to Queen Elizabeth Central Hospital, Blantyre who were diagnosed clinically with PJP was performed. All recruited infants were HIV-exposed, and the HIV status of the infant was confirmed by DNA-PCR. HIV-exposed and infected infants as well as HIV-exposed but non-infected infants were included in the study. The protocol provided for the addition of prednisolone to the treatment at 48 h if there was clinical deterioration or an independent indication for corticosteroid therapy in any patient not receiving it. Oral trimethoprim-sulfamethoxazole (TMP/SMX) therapy and full supportive treatment were provided according to established guidelines. Primary outcomes for all patients included survival to hospital discharge and 6-month post-discharge survival.. It was planned to enroll 200 patients but the trial was stopped early because of recruitment difficulties and a statistically significant result on interim analysis. Seventy-eight infants were enrolled between April 2012 and August 2014; 36 infants (46%) were randomised to receive corticosteroids plus standard treatment with TMP/SMX, and 42 infants (54%) received the standard treatment plus placebo. In an intention-to treat-analysis, the risk ratio of in-hospital mortality in the steroid group compared with the standard treatment plus placebo group was 0.53 [95% CI 0.29-0.97, p = 0.038]. The risk ratio of mortality at 6 months was 0.63 (95% CI 0.41-0.95, p = 0.029). Two children who received steroids developed bloody stools while in hospital.. In infants with a clinical diagnosis of PJP, early use of steroids in addition to conventional TMP/SMX therapy significantly reduced mortality in hospital and 6 months after discharge.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Double-Blind Method; Female; HIV Infections; Humans; Infant; Malawi; Male; Placebos; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisolone; Secondary Prevention; Survival Analysis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Before antiretroviral therapy (ART) became widely available in sub-Saharan Africa, several studies demonstrated that daily trimethoprim-sulfamethoxazole (TS) prophylaxis reduced morbidity and mortality among HIV-infected adults. As a result, the World Health Organization (WHO) recommended administering TS prophylaxis to this group. However, the applicability of the results to individuals taking ART and living in sub-Saharan Africa has not been definitively evaluated. This study aims to determine if TS prophylaxis benefits HIV-infected Malawian adults after a good response to ART. If TS prophylaxis does indeed show benefit, it is important to determine if this is due to its antibacterial and/or antimalarial properties.. A randomized, controlled, open-label, phase III trial of continued standard of care prophylaxis with daily trimethoprim-sulfamethoxazole (TS) compared to discontinuation of standard of care TS prophylaxis and starting weekly chloroquine (CQ) prophylaxis or discontinuation of standard of care TS prophylaxis. The study will randomize 1400-1500 HIV-infected adults (equally divided over the three study arms) with a nondetectable viral load and a CD4 count of 250/mm(3) or more from antiretroviral therapy clinics in Blantyre and Zomba. The expected rate of primary endpoint events of death and WHO stage 3 and 4 events is 6.8 per 100 person-years of follow-up in all participants. Assuming the number of events follows a Poisson distribution and average participant follow-up after 10 % loss to follow-up is 41.6 months, the study will have approximately 85 % power to rule out a reduction of 35 % or more in primary endpoint events in the TS or CQ arms compared to discontinuation of TS prophylaxis-i.e., to show that discontinuation of TS prophylaxis is noninferior to either TS or CQ, with a noninferiority margin of 35 %. Ethical and regulatory approvals were obtained from the University of Malawi College of Medicine Research Ethics Committee; the Malawi Pharmacy, Medicines and Poisons Board; and the University of Maryland Baltimore Institutional Review Board.. The study began recruitment activities at the Ndirande site in November 2012. The sponsor agreed to extend and expand the study in early 2015, and a second site, Zomba, was added for recruitment and follow-up in mid-2015.. ClinicalTrials.gov Identifier: NCT01650558 (registered on 6 July 2012).. Letter of amendment #1 to the DAIDS-ES 10822 TSCQ Malawi Protocol, Version 4.0, 16 December 2014.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Retroviral Agents; Antimalarials; Chloroquine; Drug Administration Schedule; HIV Infections; Humans; Malaria; Malawi; Pneumonia, Pneumocystis; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP) dosage, myelosuppression, and event-free survival (EFS) during maintenance therapy. Of 447 study patients treated by the NOPHO ALL92 protocol, 120 patients received TMP/SMX continuously for 2-7 d/wk (TMP/SMX(2-7) ) and 287 patients never received TMP/SMX (TMP/SMX(never) ). Ten patients (all TMP/SMX(never) ) developed PCP, eight of which occurred within 7 months from the start of maintenance therapy. The TMP/SMX(2-7) group received lower oral 6MP doses than TMP/SMX(never) patients (50.6 vs. 63.9 mg/m(2) /d; P<0.001) but had lower absolute neutrophil counts (ANC) (median 1.7 vs. 2.0 × 10(9) /L; P<0.001). In Cox multivariate analysis, higher ANC levels (P=0.04) and male gender (P=0.06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX(2-7) patients (P=0.40) but did for TMP/SMX(never) patients (P=0.02). The difference in the effect on EFS between TMP/SMX(2-7) and TMP/SMX(never) patients was not significant (P=0.46). EFS did not differ between TMP/SMX(2-7) and TMP/SMX(never) patients (0.83 vs. 0.83; P=0.82). These results suggest that TMP/SMX is effective in preventing PCP and may have an antileukemic effect. TMP/SMX should be given the entire duration of maintenance therapy.

Topics: Administration, Oral; Anti-Infective Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Disease-Free Survival; Female; Humans; Male; Mercaptopurine; Methotrexate; Pneumocystis carinii; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

The study aims to evaluate the efficacy of technetium-99m diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) lung clearance test in the diagnosis of pneumocystis carinii pneumonia (PCP) in HIV-positive paediatric patients. Twenty HIV-negative patients with no chest symptoms constituted Group A, 25 HIV antibody positive asymptomatic children formed Group B, while 45 HIV antibody positive children with respiratory infections comprised Group C. Group C was subdivided into C(1) (n = 20, documented PCP on microbiology), C(2) (n = 10, tuberculosis) and C(3) (n = 15, bacterial pneumonias). The mean age group of patients in Group A, Group B and Group C was 4.7 +/- 1.9, 4.2 +/- 1.5 and 4.8 +/- 1.7 years, respectively. All patients were subjected to complete blood count, blood culture, chest radiographs, microscopic staining of sputum (PCP stains, Ziehl-Nielsen staining, Gram staining), ABG and Mantoux test. All these patients underwent dynamic lung scans using (99m)Tc-DTPA aerosols and lung clearance was calculated in terms of half-time transfer value (T(1/2)) value. T(1/2) was compared between different groups and lung scan findings were correlated with radiological and microbiological results. Patients with PCP had T(1/2) in the range of 9.02 +/- 1.35, TB 28.2 +/- 3.03 min and other bacterial pneumonias in the range of 20.5 +/- 3.1 min (range for normal individuals was 49.8 +/- 6.13 min). T(1/2) in patients with PCP was found to be significantly lower when compared with T(1/2) in other groups. Patients with PCP had characteristic biphasic curves while the rest had monophasic curves. Some patients with PCP had low T(1/2) values even when chest radiographs and arterial blood gases were normal. (99m)Tc-DTPA lung clearance test is a sensitive, safe and non-invasive diagnostic tool for the early detection of PCP in HIV-positive paediatric patients.

Topics: Administration, Inhalation; Aerosols; AIDS-Related Opportunistic Infections; Child; Child, Preschool; Female; HIV Seropositivity; HIV-1; Humans; Lung; Male; Pneumonia, Pneumocystis; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Pentetate; Trimethoprim, Sulfamethoxazole Drug Combination

This article presents data from an AIDS clinical trial that evaluated 238 (60 percent nonwhite) patients infected with HIV and their clinician's perceptions of medication adherence and visit attendance in relationship to lifestyle, psychosocial, and health belief model (HBM) variables. Twelve sites collected data via a prospective, multisite observational study design involving a companion study to a larger randomized clinical trial. Baseline information was collected by questionnaire and patient self-report on lifestyle; work and health-care experiences; available support; and psychosocial issues, including the HBM constructs. At follow-up visits, clinicians and patients graded medication adherence using the same scale. Patients confidentially reported follow-up information about lifestyle and answered HBM questions. After 12 months, adherence with study visits was associated with older age. Clinicians rated patients as having good adherence significantly more often when those patients were older, were employed at the time of enrollment, exhibited altruism as part of the reason for enrolling in the clinical trial, and thought HIV was very serious. Patients rated themselves as having good adherence significantly more often if they were older, had family or friends who were infected with HIV, and believed that being in the study was worth the trouble.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Data Collection; Humans; Logistic Models; Middle Aged; Patient Compliance; Pneumonia, Pneumocystis; Prospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

In the CHAP randomized placebo-controlled trial of cotrimoxazole prophylaxis in HIV-infected Zambian children conducted between 2001 and 2003, cotrimoxazole was associated with significant mortality reductions. In a secondary analysis we used Cox regression models to estimate the association between adherence measured by bottle weights and caregiver report and subsequent mortality in children surviving >28 days (n = 496, 153 deaths). Adherence was high and similar in both cotrimoxazole and placebo groups; adherence from bottle weights was 100% at 71% of visits, while caregivers reported 100% adherence at 79% of visits. Every 10% lower adherence to cotrimoxazole or placebo measured by bottle weights was associated with a 10-11% increase in mortality risk. Effects remained after adjustment for baseline predictors of survival and for current and recent change in primary caregiver. Caregiver-reported adherence was not associated with survival. The association between bottle-weight adherence to placebo and survival is likely capturing unmeasured caregiver effects, whose identification will be essential for quantifying the impact of antiretroviral therapy (ART) adherence on clinical outcomes in children.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Caregivers; Child; Child, Preschool; Humans; Infant; Medication Adherence; Pneumonia, Pneumocystis; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

Trimethoprim-sulfamethoxazole (TMP-SMZ) has been used extensively for the prevention of Pneumocystis carinii (also referred to as "Pneumocystis jiroveci") pneumonia (PCP) and other opportunistic infections in human immunodeficiency virus (HIV)-infected children. Because the efficacy of TMP-SMZ for treatment of bacterial infections is limited, it is sometimes poorly tolerated, and there is risk of emergence of drug-resistant strains associated with widespread use, we evaluated a regimen that included atovaquone and azithromycin.. A randomized, double-blind, placebo-controlled trial was designed to determine whether atovaquone-azithromycin had equivalent efficacy to TMP-SMZ for the prevention of serious bacterial infections and to compare the long-term tolerance, PCP breakthrough rates, and nonserious bacterial infection rates among HIV-infected children aged 3 months to 19 years. Children qualified for PCP prophylaxis (on the basis of Centers for Disease Control and Prevention recommendations) were randomized to receive atovaquone-azithromycin or TMP-SMZ daily for >or=2 years.. Data from 366 of the 369 eligible patients (median duration of follow-up, 3 years) showed that the estimated rates of serious bacterial infection-related events were lower among atovaquone-azithromycin recipients than among TMP-SMZ recipients (17.3 vs. 24.2 events per 100 patient-years; difference, 6.9 events per 100 patient-years; 95% confidence interval [CI], -0.22 to 14.12). Rates for all end points (serious bacterial infection, PCP, Mycobacterium avium complex infection, and serious and nonserious bacterial infection-related deaths) were 19.7 and 27.7 events per 100 patient-years, respectively (difference, 7.9 events per 100 patient-years; 95% CI, -0.28 to 15.54 events per 100 patient-years). The results marginally favored atovaquone-azithromycin therapy statistically. Atovaquone-azithromycin and TMP-SMZ therapies had similar adverse event profiles.. We conclude that, in HIV-infected children, atovaquone-azithromycin is as effective as TMP-SMZ for the prevention of serious bacterial infections and is similarly tolerated.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Atovaquone; Azithromycin; Bacterial Infections; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Humans; Infant; Infant, Newborn; Male; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The benefits of trimethoprim-sulfamethoxazole (TS) prophylaxis reported for persons living with HIV in Cote d'Ivoire are difficult to extrapolate to sub-Saharan African countries where bacterial resistance to TS is higher and cross-resistance between TS and sulfadoxine-pyrimethamine (SP) may impair SP efficacy for malaria treatment. We conducted a community-based cohort study to measure the incidence of potentially TS-preventable illnesses in Blantyre, Malawi. We found a high incidence of malaria, invasive bacterial infections, and probable bacterial pneumonias but low rates of Pneumocystis jiroveci pneumonia, isosporiasis, and Toxoplasma encephalitis. Most bacterial isolates were resistant to TS but sensitive to azithromycin, a possible alternative to TS. Clinical trials are needed to determine the role of TS or alternative regimens for prophylaxis against secondary infections among people living with HIV in sub-Saharan Africa. These should also assess benefit in patients receiving antiretroviral therapy.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Azithromycin; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Humans; Malaria; Malawi; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy.. We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter.. The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (758 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (123 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.5 episodes per 100 person-years).. In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; HIV Infections; HIV-1; Humans; Male; Multivariate Analysis; Pneumonia, Pneumocystis; RNA, Viral; Statistics, Nonparametric; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the incidence and determinants of bacteremia, pneumonia, and sinusitis/otitis in HIV-positive people receiving cotrimoxazole (CTX) or dapsone-pyrimethamine (DP) for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) within a randomized clinical trial. In total, 244 patients were randomized: 122 were assigned to CTX and 122 to DP. In the cohort, 22 bacteremia, 63 pneumonia, and 39 sinusitis/otitis cases were observed. Incidence rates of bacteremia, pneumonia, and sinusitis/otitis as well as the 2-year probability of remaining free from any bacterial infection were not significantly different between the two groups. At multivariate analysis, the risks of developing bacteremia and pneumonia were found to be independently increased by the use of a central venous catheter (hazard ratio [HR], 4.48; p <.05 and HR, 4.13; p <.01, respectively) and by hospitalization (HR, 28.82; p <.05 and HR, 10.15; p <.05, respectively). In conclusion, CTX at the dosage employed for primary PCP/TE prophylaxis does not seem to protect against bacterial infections more than second-line DP.

Topics: Adult; Animals; Anti-Infective Agents; Bacterial Infections; Dapsone; Encephalitis; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Pneumocystis; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMZ) is the most effective Pneumocystis carinii pneumonia (PCP) prophylactic agent, but adverse reactions are common among human immunodeficiency virus (HIV)-infected patients and limit its use. This randomized, double-blind controlled trial compared 2 methods of TMP-SMZ reintroduction, 6-day dose escalation and direct rechallenge, for PCP prophylaxis in HIV-infected patients who had experienced previous treatment-limiting reactions. The primary end point was the ability to take single-strength TMP-SMZ daily for 6 months. Seventy-five percent of the dose-escalation group and 57% of the direct-rechallenge group continued to receive daily single-strength TMP-SMZ for 6 months (P= .014). Among premature discontinuations, 58% of the dose-escalation group and 70% of the direct-rechallenge group were due to adverse reactions. None of these reactions was serious. This study provides evidence that it is possible to successfully reintroduce TMP-SMZ to a significant proportion of HIV-infected patients who have experienced mild-to-moderate treatment-limiting adverse reactions.

Topics: Adult; Antiretroviral Therapy, Highly Active; Dose-Response Relationship, Drug; Double-Blind Method; Female; HIV Infections; Humans; Male; Middle Aged; Patient Selection; Pneumonia, Pneumocystis; Racial Groups; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The relationship between the onset of adverse events to cotrimoxazole in HIV-infected patients and the subsequent development of toxoplasmosis, other AIDS-defining events and survival was studied in 592 French patients who first received cotrimoxazole during the Delta trial. Low CD4+ cell count at cotrimoxazole introduction was the only factor associated with the onset of adverse reactions. The occurrence of toxoplasmosis and first AIDS-defining events were significantly and independently linked to a low CD4+ cell count at cotrimoxazole introduction (p < 0.0001) and to previous cotrimoxazole withdrawal for adverse events (p = 0.004 and p < 0.0001, respectively), but not to previous cotrimoxazole withdrawal for reasons other than adverse events, as compared to patients who did not discontinue taking cotrimoxazole during this survey. The survival rate was significantly shorter among both patients who stopped taking cotrimoxazole for adverse events and for other reasons (p = 0.03 and p = 0.0001, respectively), as compared to patients who continued to take cotrimoxazole.

Topics: Adult; AIDS-Related Opportunistic Infections; Analysis of Variance; Anti-Infective Agents; Disease Progression; Double-Blind Method; Drug Eruptions; Female; France; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Survival Rate; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

A multicenter open, randomized, controlled trial was conducted to determine whether primary prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis can be discontinued in patients infected with human immunodeficiency virus type 1 (HIV-1) whose CD4+ T cell counts have increased to >200 cells/mm3 (and who have remained at this level for at least 3 months) as a result of highly active antiretroviral therapy (HAART). Patients were randomized to either the discontinuation arm (i.e., those who discontinued prophylaxis; n=355) or to the continuation arm (n=353); the 2 arms of the study were similar in terms of demographic, clinical, and immunovirologic characteristics. During the median follow-ups of 6.4 months (discontinuation arm) and 6.1 months (continuation arm) and with a total of 419 patient-years, no patient developed P. carinii pneumonia or toxoplasmic encephalitis. The results of this study strongly indicate that primary prophylaxis for P. carinii pneumonia and toxoplasmic encephalitis can be safely discontinued in patients whose CD4+ T cell counts increase to >200 cells/mm3 during HAART.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antiprotozoal Agents; CD4 Lymphocyte Count; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Italy; Male; Middle Aged; Paris; Pentamidine; Pneumonia, Pneumocystis; Time Factors; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

This study was conducted to determine whether Pneumocystis carinii dyhydropteroate synthase (DHPS) gene mutations in AIDS patients with P. carinii pneumonia (PCP) are affected by duration of sulfa or sulfone prophylaxis and influence response to sulfa or sulfone therapy. The P. carinii DHPS genes from 97 AIDS patients with PCP between 1991 and 1999 from 4 medical centers were amplified, using polymerase chain reaction (PCR), and sequenced. Mutations were observed in 76% of isolates from patients exposed to sulfa or sulfone prophylaxis compared with 23% of isolates from patients not exposed (P=.001). Duration of prophylaxis increased the risk of mutations (relative risk [RR] for each exposure month, 1.06; P=.02). Twenty-eight percent of patients with mutations failed sulfa or sulfone treatment; mutations increased the risk of sulfa or sulfone treatment failure (RR, 2.1; P=0.01). Thus, an increased duration of sulfa or sulfone prophylaxis increases the chance of developing a P. carinii mutation. The majority of patients with mutations respond to sulfa or sulfone therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Dapsone; Dihydropteroate Synthase; Female; Humans; Male; Middle Aged; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Sulfones; Trimethoprim, Sulfamethoxazole Drug Combination; United States

AIDS Clinical Trial Group (ACTG) randomized trial 021 compared the effect of bactrim versus aerosolized pentamidine (AP) as prophylaxis therapy for pneumocystis pneumonia (PCP) in AIDS patients. Although patients randomized to the bactrim arm experienced a significant delay in time to PCP, the survival experience in the two arms was not significantly different (p = .32). In this paper, we present evidence that bactrim therapy improves survival but that the standard intent-to-treat comparison failed to detect this survival advantage because a large fraction of the subjects either crossed over to the other therapy or stopped therapy altogether. We obtain our evidence of a beneficial bactrim effect on survival by artificially regarding the subjects as dependently censored at the first time the subject either stops or switches therapy; we then analyze the data with the inverse probability of censoring weighted Kaplan-Meier and Cox partial likelihood estimators of Robins (1993, Proceedings of the Biopharmaceutical Section, American Statistical Association, pp. 24-33) that adjust for dependent censoring by utilizing data collected on time-dependent prognostic factors.

Topics: Acquired Immunodeficiency Syndrome; Aerosols; AIDS-Related Opportunistic Infections; Algorithms; Anti-Infective Agents; Biometry; Humans; Models, Statistical; Multicenter Studies as Topic; Pentamidine; Pneumonia, Pneumocystis; Probability; Randomized Controlled Trials as Topic; Reproducibility of Results; Survival Rate; Treatment Refusal; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) is recognized as the superior agent for Pneumocystis carinii pneumonia (PCP) prophylaxis but a high incidence of adverse drug reactions, which may be due to toxic drug metabolites, limits its use. AIDS Clinical Trials Group protocol 268 was a randomized, double-blind, controlled two-arm trial designed to determine whether gradual initiation of TMP/SMX suspension reduced the incidence of treatment-limiting adverse drug reactions compared with routine initiation of double-strength (DS; 160 mg/800 mg) tablets. In all, 372 HIV-1-infected study subjects with a CD4+ cell count <250 x 10 cells/mm3 who had not previously received TMP/SMX for PCP prophylaxis were randomized to receive either daily TMP/SMX DS tablets or a gradually increasing dose of TMP/SMX suspension. The suspension dose was increased to reach the equivalent of a DS tablet by study day 13. During the first 2 weeks, study subjects also received a matching placebo tablet/suspension. After week 2, all study subjects received TMP/SMX tablets for the next 10 weeks. There were significantly fewer study subjects who discontinued prophylaxis during the first 12 weeks when TMP/SMX therapy was initiated gradually (17%) than when initiated in DS tablet formulation (33%) (p =.0002). Gradual initiation was also associated with significantly fewer adverse drug reactions. Gradual initiation of TMP/SMX for primary PCP prophylaxis reduces the incidence of its treatment-limiting adverse effects.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Double-Blind Method; Drug Eruptions; Female; Fever; HIV Infections; HIV-1; Humans; Male; Nausea; Pneumonia, Pneumocystis; Pruritus; Trimethoprim, Sulfamethoxazole Drug Combination

Clinical trials often assess therapeutic benefit on the basis of an event such as death or the diagnosis of disease. Usually, there are several additional longitudinal measures of clinical status which are collected to be used in the treatment comparison. This paper proposes a simple non-parametric test which combines a time to event measure and a longitudinal measure so that a substantial treatment difference on either of the measures will reject the null hypothesis. The test is applied on AIDS prophylaxis and paediatric trials.

Topics: Acquired Immunodeficiency Syndrome; Anti-HIV Agents; Anti-Infective Agents; Antifungal Agents; Candidiasis; Child; Child, Preschool; Clinical Trials as Topic; Clotrimazole; Dapsone; Didanosine; Drug Therapy, Combination; Fluconazole; Head; Humans; Longitudinal Studies; Pentamidine; Pneumonia, Pneumocystis; Statistics, Nonparametric; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Pneumonia due to Pneumocystis carinii is an infrequent complication following autologous stem cell transplantation (ASCT) which is associated with a high mortality. Although administration of trimethoprim/sulfa- methoxazole (TMP/SMX) is an effective prophylactic strategy for Pneumocystis carinii pneumonia (PCP), treatment-associated toxicity frequently results in discontinuation of therapy. We have conducted a prospective randomized trial comparing atovaquone, a new anti-Pneumocystis agent, with TMP/SMX for PCP prophylaxis following autologous peripheral blood stem cell (PBSC) transplantation. Thirty-nine patients were studied. Twenty patients received atovaquone suspension and 19 patients received TMP/SMX. The median ages were 44 (range 20-68) and 47 (range 32-63) years, respectively. A similar number of patients with solid tumors (14 vs 15) and hematologic malignancies (five vs five) were treated in each group. Either TMP/SMX (160/800 mg) or atovaquone (1500 mg) was administered daily from transplant day -5 until day -1, discontinued from day 0 to engraftment, then resumed 3 days per week until day +100 post-transplant. The median time to engraftment (ANC >0.5 x 109/l) was similar in both groups. Eighty percent of the patients randomized to atovaquone prophylaxis completed the study. Four atovaquone-treated patients were removed from study; two patients (10%) did not receive a transplant and two patients (10%) were removed due to a protocol violation. None of the 16 patients treated with atovaquone experienced treatment-associated adverse effects. Of the 19 patients randomized to receive TMP/SMX, 55% completed the study. Nine TMP/SMX-treated patients were removed from the study; one patient (5%) did not receive a transplant and eight patients (40%) were removed due to drug intolerance (P < 0.003). The rate of intolerance to TMP/SMX led to the early discontinuation of this randomized trial. Intolerance of TMP/SMX included elevated transaminase levels (n = 1), nausea or vomiting (n = 3), thrombocytopenia (n = 2) and neutropenia (n = 2). All episodes of TMP/SMP intolerance occurred following transplantation after a median duration of 17.5 (range 2-48) days and a median of 7 (range 1-20) doses. Resolution of adverse side-effects occurred in all eight patients within a median of 7 (range 2-20) days following discontinuation of therapy. Neither PCP nor bacterial infections were identified in any of the patients treated. This prospective randomized study demon

Topics: Adult; Aged; Antifungal Agents; Atovaquone; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Male; Middle Aged; Naphthoquinones; Neoplasms; Pneumocystis; Pneumonia, Pneumocystis; Prospective Studies; Transplantation, Autologous; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We conducted a prospective, randomized clinical trial among liver transplant patients to assess the efficacy and safety of weekly sulfadoxine/pyrimethamine compared with daily trimethoprim-sulfamethoxazole in the prevention of Pneumocystis carinii pneumonia. The studied drugs were given during 6 months after transplantation. One hundred twenty patients were included. None of the 60 patients receiving weekly sulfadoxine/pyrimethamine developed Pneumocystis carinii pneumonia, whereas two cases (3%) developed among the 60 patients who received trimethoprim-sulfamethoxazole. For both patients, the studied medication had been discontinued several weeks earlier because of adverse effects. No differences were observed in the incidence of adverse effects. We conclude that weekly sulfadoxine/pyrimethamine is as effective and safe as is daily trimethoprim-sulfamethoxazole in the prophylaxis of Pneumocystis carinii pneumonia after liver transplantation.

Topics: Adult; Aged; Anti-Infective Agents; Drug Combinations; Female; Humans; Liver Transplantation; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination

We enrolled 2,625 human immunodeficiency virus-infected patients into a randomized trial to assess the efficacy and tolerability of daily vs. thrice-weekly trimethoprim-sulfamethoxazole (160 mg/800 mg) for prophylaxis of Pneumocystis carinii pneumonia (PCP). The rate of PCP was 3.5 and 4.1 per 100 person-years in the daily and thrice-weekly groups, respectively, with a relative risk (RR) of 0.82 (95% confidence interval [CI], 0.61-1.09; P = .16) (RR of <1.0 favors daily trimethoprim-sulfamethoxazole). The RR for PCP determined by on-treatment analysis was 0.59 (P = .03). The RR for death was 0.91 (P = .12); for bacterial pneumonia, 0.82 (P = .06); and for combined PCP and bacterial pneumonia, 0.84 (P = .04). Discontinuation due to adverse events occurred more commonly in the daily trimethoprim-sulfamethoxazole group (RR, 2.14; 95% CI, 1.73-2.66; P < .001). Overall estimates for efficacy end points favored daily trimethoprim-sulfamethoxazole, although rates of intolerance were higher among patients receiving that dose. Daily trimethoprim-sulfamethoxazole may offer advantages as a first choice for PCP prophylaxis; thrice-weekly dosing is an appropriate option for patients intolerant of the daily dose.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the pharmacokinetics and safety of atovaquone suspension in volunteers infected with the human immunodeficiency virus ((HIV).. Open-label, nonrandomized study.. Two clinical research centers.. Twenty-two HIV-infected volunteers with a median CD4 cell count of 37 cells/mm3.. Patients received atovaquone suspension fasting or fed for 2-week periods with crossover at dosages of 500 mg/day, and randomization to fasting or fed at dosages of 750 and 1000 mg/day. A subset of patients also received 750 mg twice/day with food, and a subset of those who received 1000 mg/day fasting also received 1000 mg with food. During a long-term dosing phase, a subset of subjects were evaluated for an interaction between atovaquone and trimethoprim-sulfamethoxazole (TMP-SMX).. Average steady-state atovaquone concentrations at 500 mg were 6.7 +/- 3.2 microg/ml fasted and 11.3 +/- 5.0 microg/ml with food; at 750 mg, 9.9 +/- 7.1 microg/ml fasted and 12.5 +/- 5.9 microg/ml with food; at 1000 mg, 9.7 +/- 4.3 microg/ml fasted and 13.6 +/- 5.0 microg/ml with food; and at 1500 mg, 21.1 +/- 5.0 microg/ml with food. Thus, plasma concentrations were not proportional to dose. Concomitant food ingestion resulted in a 1.3- to 1.7-fold increase in values. Average steady-state concentrations were less than 10 microg/ml in 21% and more than 15 microg/ml in 36% of patients at 1000 mg/day with food; at 750 mg twice/day, all five patients had levels above 15 microg/ml. Atovaquone suspension was well tolerated; diarrhea, nausea, fatigue, and rash were the most common adverse events. Concomitant administration of TMP-SMX did not change atovaquone concentrations and resulted in small decreases in concentrations of TMP (16%) and SMX (10%).. Plasma concentrations are significantly higher when atovaquone suspension is administered with food compared with fasting. Total doses of 1500 mg/day are likely to achieve concentrations effective for prophylaxis of Pneumocystis carinii pneumonia.

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Fasting; Female; Food-Drug Interactions; Humans; Male; Middle Aged; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The efficacy and adverse effects of prophylactic administration of Sulfamethoxazole-Trimethoprim (ST) for Pneumocystis carinii Pneumonia (PCP) were assessed in patients with connective tissue diseases (CTD). Eighty-four patients who were receiving more than 40 mg/day of prednisolone were entried in the present study. Patients with at least one of the two PCP risk factors (interstitial pulmonary fibrosis and lymphopenia), were administered either one (11 patients) or two (26 patients) ST tablets/day. The remaining 47 patients who did not receive ST served as the controls. Although PCP was detected in 4.3% of the patients in the no-ST group, none of the patients who received ST developed PCP. Five of these 26 patients who received two tablets of ST/day, experienced adverse reactions. However, no adverse reactions were detected in the patients who received one tablet of ST/day (p < 0.05). Abnormal laboratory data were obtained for 10 (38.5%) of the patients who received two tablets of ST/day and for 4 (36.4%) of the 11 patients who received one tablet of ST/day. The results of the present study suggest that the prophylactic administration of one tablets of ST in patients with CTD that have at least one of the two PCP risk factors is effective in preventing PCP.

Topics: Adult; Anti-Infective Agents; Connective Tissue Diseases; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Pneumonia, Pneumocystis; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Double-Blind Method; Humans; Pneumonia, Pneumocystis; Senegal; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

The pathogenesis of hypersensitivity to trimethoprim-sulfamethoxazole (TMP-SMX) is supposed to be associated with the slow acetylation phenotype. This pharmacogenetic defect is associated with the mutations of the arylamine N-acetyltransferase (NAT2) encoding gene. The aim of the study was to compare the usefulness of the acetylation phenotype and NAT2 coding genotype in the prediction of idiosyncratic reaction to Cotrimoxazole in infants. The study was carried out in the group of 20 infants, aged 2-12 months (mean age 6.3 months) treated with Cotrimoxazole, administered at 100 mg/kg b.w./24 h doses. In seven children (35%) no adverse effects of the treatment have been observed, whereas in 13 (65%) children various adverse effects occurred as a result of the therapy, such as rash (4 children), granulocytopenia with anemization (5 children) or liver impairment (4 children). The acetylation phenotype of each child was determined on the basis of urine of N-acetyl isoniazid/isoniazid ratio, after ingestion of isoniazid as a model drug. Furthermore we used polymerase chain reaction (PCR) followed by the analysis of restriction fragments length polymorphism (RFLP) technique to identify the known mutant alleles of the NAT2 gene. It has been presumed that the genotype determining fast acetylation contains at least one of wild-type allele. No correlation has been found between the observed adverse effects of Cotrimoxazole and age, gender and acetylation phenotype. However, it has been demonstrated that the risk of adverse effects of Cotrimoxazole is considerably higher in children with mutations of the NAT2 encoding gene. The comparison of the results from PCR-RFLP genotyping with phenotyping suggested that in infants, the NAT2 genotype rather than phenotype provides the basis for the detection of hypersensitivity to TMP-SMX.

Topics: Acetylation; Alleles; Anti-Infective Agents; Arylamine N-Acetyltransferase; Drug Hypersensitivity; Female; Genotype; Humans; Infant; Male; Pneumonia, Pneumocystis; Poland; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Trimethoprim, Sulfamethoxazole Drug Combination

This double-blind, randomized, multicenter trial compared clindamycin/primaquine (Cm/Prq) with trimethoprim-sulfamethoxazole (TMP-SMZ) as therapy for AIDS-related Pneumocystis carinii pneumonia (PCP). Forty-five patients received clindamycin (450 mg four times daily [q.i.d.]) and primaquine (15 mg of base/d); 42 received TMP-SMZ (320 mg/1,600 mg q.i.d. if weight of > or = 60 kg or 240 mg/1,200 mg q.i.d. if weight of < 60 kg) plus placebo primaquine. Overall, the efficacy of Cm/Prq was similar to that of TMP-SMZ (success rate, 76% vs. 79%, respectively); Cm/Prq was associated with fewer adverse events (P = .04), less steroid use (P = .18), and more rashes (P = .07). These differences were even greater for patients with PaO2 of > 70 mm Hg (P = .02, P = .04, and P = .02, respectively). For patients with PaO2 of < or = 70 mm Hg (23 Cm/Prq recipients and 21 TMP-SMZ recipients), the efficacy of Cm/Prq was similar to that of TMP-SMZ (success rate, 74% vs. 76%, respectively); Cm/Prq was associated with similar adverse events (P = .57), steroid use (P = .74), and rashes (P = .78). This trial confirms that Cm/Prq is a reasonable alternative therapy for mild and moderately severe PCP.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Clindamycin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Pneumonia, Pneumocystis; Primaquine; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

In 1995 and 1997, the United States Public Health Service (USPHS) and the Infectious Disease Society of America (IDSA) published recommendations for primary prophylaxis of Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), and toxoplasmosis in HIV-infected adults. We evaluated their implementation at four hospital-based HIV clinics in New York City in patients who initially met the CD4+ criterion for prophylaxis between January, 1995 and April, 1997. Medical records were reviewed at 6-month intervals to determine drugs prescribed. We identified 149 patients for the PCP sample, 130 for MAC, and 138 for toxoplasmosis. In the three samples, 91% were black and Hispanic, 75% to 81% were male, and 43% to 47% had a history of injection drug use (IDU); median age was between 39 and 40 years. PCP prophylaxis was prescribed during 93% of intervals and did not vary significantly by clinic or patient characteristics. Over the study period, MAC prophylaxis increased from 22% to 62%, and prescriptions for macrolides increased from 38% to 87% of all prescriptions. In the logistic regression analysis, prescription for MAC prophylaxis at any time during the study period was less likely in blacks compared with whites (odds ratio [OR] = .08; 95% confidence interval [CI] = .01, .52) and patients attending the clinic with the lowest rate of MAC prophylaxis (clinic D) compared with the clinic with the highest rate (clinic B; OR = .04; 95% CI = .01, .26). Toxoplasmosis prophylaxis was prescribed in 73% of intervals and did not differ significantly by antibody status (p = .42). Prescribing patterns were uniform across gender, HIV risk behavior, and age for PCP and MAC prophylaxis but differed by clinic and race for MAC prophylaxis. Trends in prophylaxis for opportunistic illnesses must continue to be monitored in light of the success of antiretroviral therapy in reducing the morbidity and mortality associated with HIV/AIDS.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Analysis of Variance; Anti-Infective Agents; Atovaquone; Azithromycin; Clarithromycin; Dapsone; Ethnicity; Female; HIV Infections; Humans; Longitudinal Studies; Male; Medical Records; Mycobacterium avium-intracellulare Infection; Naphthoquinones; New York City; Pentamidine; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Regression Analysis; Rifabutin; Risk-Taking; Time Factors; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Public Health Service

Hydroxylamine derivatives of sulfamethoxazole may be the reactive metabolites that cause adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMX). The increased frequency of reactions observed in HIV-positive individuals is hypothesized to be due to systemic glutathione deficiency and a decreased ability to scavenge these metabolites. Two hundred and thirty-eight patients were randomized to receive or not receive N-acetylcysteine (3 g of the 20% liquid solution) 1 hour before each dose of TMP-SMX (trimethoprim 80 mg, sulfamethoxazole 400 mg) twice daily, which was initiated as primary Pneumocystis carinii pneumonia prophylaxis. Forty-five patients had to discontinue TMP-SMX within 2 months because of fever, rash, or pruritus including 25 of 102 patients (25%) who were receiving TMP-SMX alone and 20 of 96 patients (21%) who were randomized to TMP-SMX and N-acetylcysteine. The difference between treatment groups is 4% (95% confidence interval [CI]: -16%, +9%). No independent association was found with the hypersensitivity reaction and age, gender, race, HIV risk factor, prior AIDS, concurrent use of fluconazole, or baseline CD4. N-acetylcysteine at a dose of 3 g twice daily could not be shown to prevent TMP-SMX hypersensitivity reactions in patients with HIV infection.

Topics: Acetylcysteine; Adult; Anti-Infective Agents; Drug Hypersensitivity; Female; Free Radical Scavengers; HIV Infections; Humans; Incidence; Male; Middle Aged; Outcome Assessment, Health Care; Pneumonia, Pneumocystis; Primary Prevention; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Although trimethoprim-sulfamethoxazole is the drug of choice for the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent.. We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500-mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim-sulfamethoxazole. The median follow-up period was 27 months.. Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia. P. carinii pneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P<0.001); among those not receiving dapsone at base line, it was 0.42 (95 percent confidence interval, 0.30 to 0.58; P<0.001).. Among patients who cannot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention of P. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. carinii pneumonia.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Atovaquone; Dapsone; Female; Follow-Up Studies; HIV Infections; Humans; Male; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

We studied the relation between the occurrence of adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis and the subsequent course of human immunodeficiency virus (HIV) infection in a cohort of homosexual men. Adverse reactions to TMP-SMZ were associated with a more rapid progression to AIDS (P < .001) and death (P < .001) and with a more rapid decline in CD4+ cell counts (P = .001). The median time to progression to AIDS was 14.9 months in subjects with adverse reactions to TMP-SMZ and 32.5 months in those without adverse reactions. After exclusion of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis from the case definition of AIDS, the differences in the rate of progression to AIDS between subjects with and without adverse reactions to TMP-SMZ were still highly significant (P = .004). A low CD4+ cell count at baseline and the use of antiretroviral agents before the start of prophylaxis were predictors of adverse reactions to TMP-SMZ but did not account for the difference in progression to AIDS between subjects with and without adverse reactions to TMP-SMZ. In a univariate analysis, the relative hazard of adverse reactions to TMP-SMZ for progression to AIDS was 2.54 (95% confidence interval [CI], 1.50-4.28); in a multivariate analysis, it was 2.21 (95% CI, 1.29-3.81). The relative hazards of adverse reactions to TMP-SMZ for progression to AIDS with the exclusion of PCP and toxoplasmosis, CD4+ cell counts of <50/mm3, and death were 2.16 (95% CI, 1.25-3.72), 2.37 (95% CI, 1.36-4.12), and 3.21 (95% CI, 1.80-5.72), respectively. It is unclear whether adverse reactions to TMP-SMZ induce or merely predict progression of HIV disease.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cohort Studies; Disease Progression; HIV Infections; HIV-1; Homosexuality, Male; Humans; Logistic Models; Male; Pneumonia, Pneumocystis; Primary Prevention; Prognosis; Prospective Studies; Survival Rate; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

In a randomized double blind placebo controlled trial, HIV sero-positive patients with CD4+ cell count less than 200 x 10(6)/l or an AIDS diagnosis were evaluated for drug reactions to trimethoprim-sulphamethoxazole (TMP-SMX) during treatment, including pretreatment, with N-acetylcysteine (NAC) 800 mg daily or placebo. TMP-SMX (one double-strength tablet containing 160 mg of trimethoprim and 800 mg of sulphamethoxazole) was given three times weekly as primary Pneumocystis carinii (PCP) prophylaxis. Thirty percent (n = 15) of the patients experienced adverse reactions 8-20 (mean 12.7) days after starting with TMP-SMX. At entry, low cysteine and glutathione levels in plasma were found in the HIV-positive patients. Age, sex, CD4+ count, plasma cysteine and glutathione levels were not risk factors for adverse reactions to TMP-SMX. However, concomitant therapy with nucleoside analogues was associated with increased risk for TMP-SMX reactions. Oral NAC 800 mg daily was well tolerated, but replenished neither cysteine nor glutathione levels in plasma. NAC 800 mg/day did not significantly decrease the risk of adverse reactions to TMP-SMX in this study, and could thus not be recommended for this purpose. A prolonged pretreatment period and/or higher dose of NAC may be necessary for clinical effect.

Topics: Acetylcysteine; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cysteine; Exanthema; Female; Fever; Glutathione; Humans; Male; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Injections, Intravenous; Male; Pentamidine; Pneumonia, Pneumocystis; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) is the most common opportunistic human immunodeficiency virus (HIV)-related infection, occurring in 85% of HIV infected patients without prophylaxis. Preventive treatment is required when CD4 cell count falls below 200 cells per cubic millimeter. Cotrimoxazole has been shown to be highly effective but alternative drug regimens are often necessary because of the frequent drug hypersensitivity exhibited by HIV infected patients. The aim of this prospective, open, randomized, one-site study, involving HIV-infected patients with a CD4 cell count below 200/mm3, or a percentage under 20%, randomly assigned to receive either dapsone 50 mg daily or Fansidar one tablet weekly, was to compare the efficacy and safety of these drugs in the primary prophylaxis of PCP. Both dapsone and Fansidar appear to be safe and effective alternative agents for the prevention of PCP. Their role in Toxoplasma gondii prophylaxis requires further evaluation.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Dapsone; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Pyrimethamine; Sulfadoxine; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia.. A randomized, double-blind study.. 24 U.S. academic medical centers.. 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less.. Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone.. Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions.. No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P=0.2), therapeutic failure (P>0.2), or a complete course of therapy (P>0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P>.02). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P=0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P=0.01).. The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Clindamycin; Dapsone; Double-Blind Method; Drug Therapy, Combination; Female; Hematologic Diseases; Humans; Male; Pneumonia, Pneumocystis; Primaquine; Prospective Studies; Quality of Life; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the long-term feasibility, safety, and tolerability of two regimens of aerosolized pentamidine (AP) as primary prophylaxis of Pneumocystis carinii pneumonia (PCP) in a large sample of infants and children with symptomatic HIV infection in 21 pediatric departments. One hundred forty children were assigned to receive 60 mg every 2 weeks (n = 60) or 120 mg every 4 weeks (n = 80) of AP, delivered by the ultrasonic nebulizer Fisoneb under the supervision of trained personnel. Children underwent monthly clinical and laboratory controls for toxicity and/or development of PCP for an 18-month period. Baseline characteristics were similar in the two treatment groups. The median age was 5 years. The feasibility of administering AP was excellent in 84 (60 percent) and good in 38 (27 percent) children. All children aged <2 years showed excellent or good feasibility. Long-term compliance was good with both regimens. No child had severe adverse reactions requiring discontinuation of the treatment. Cough, sneezing, and bronchospasm were the most frequent side effects occurring, respectively, in 12, 3.7, and 0.7 percent of the 60-mg treatments and in 19.1, 6. 1, and 2.8 percent of 120-mg treatments (p < 0.05). Their incidence was not different in children younger or older than 5 years. Two episodes of PCP were observed in the group receiving 120 mg monthly, whereas none of the 60 children in the biweekly schedule had PCP (p = 0.20). AP can be safely administered to very young children with few adverse side effects.

Topics: Adolescent; Aerosols; AIDS-Related Opportunistic Infections; Antifungal Agents; Child; Child, Preschool; Drug Administration Schedule; Drug Tolerance; Female; Humans; Infant; Male; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Safety; Trimethoprim, Sulfamethoxazole Drug Combination

We randomized 220 HIV-1-infected subjects to receive aerosolized pentamidine (300 mg/4 weeks) or orally trimethoprim-sulfamethoxazole (320-1600 mg/day) for primary prophylaxis of Pneumocystis carinii pneumonia (PCP), and evaluated PCP and toxoplasmic encephalitis (TE) occurrence and survival. Patients developing toxicity switched to the other regimen. Analysis was on intention-to-treat. At 1 year of study, we observed in the pentamidine group a non-significant excess of PCP (4 vs. 1) and TE (7 vs. 3), and a significant increased death rate (15 vs. 2). After 2 years, no significant differences were observed: adjusted RR estimates for pentamidine vs. cotrimoxazole were 1.20 (95% CI, 0.33-4.37) for PCP (6 cases vs. 5), 1.23 (95% CI, 0.46-3.29) for TE (10 vs. 8) and 1.52 (95% CI, 0.83-2.79) for death (30 vs. 18). Crossovers were more frequent in the cotrimoxazole group (41 vs. 4, P < 0.001). Aerosolized pentamidine and cotrimoxazole were equally effective in preventing PCP, and no major differences were observed in TE occurrence and survival after 2 years follow-up.

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Female; HIV-1; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Pharmacokinetic parameters of zidovudine (ZDV) were not altered in 16 patients receiving concomitant therapy with ZDV and trimethoprim-sulfamethoxazole by oral administration. ZDV areas under the concentration-time curves were (means +/- standard deviations) 1.80 +/- 0.70 and 1.69 +/- 0.64 micrograms.h/ml in the absence and presence of trimethoprim-sulfamethoxazole, respectively. ZDV clearances were 1.57 +/- 0.61 and 1.74 +/- 0.66 liters/h/kg, respectively.

Topics: Adult; Antifungal Agents; Antiviral Agents; Drug Interactions; Female; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dapsone; Drug Therapy, Combination; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Although the reported incidence of Pneumocystis carinii pneumonia after heart transplantation in adults ranges from 3% to 40%, data are lacking regarding the incidence in the pediatric heart transplantation population. A retrospective review was performed on 152 infants (0 to 12 months of age) undergoing transplantation from November 1985 through December 1993 who survived at least 6 months after heart transplantation. Patients did not receive postoperative Pneumocystis carinii prophylaxis. Ten episodes (7%) were diagnosed in four neonates and six infants. The mean postoperative time to Pneumocystis carinii diagnosis was 5 months (range 3 to 9 months). Features of Pneumocystis carinii included hypoxia and tachypnea (10 of 10), progressive interstitial infiltrates (8 of 10), and persistent right middle lobe consolidation (1 of 10). Pneumocystis carinii was diagnosed with the use of bronchoscopy in eight cases and by open lung biopsy in two cases. Mean CD4 count available on five patients at the time of Pneumocystis carinii diagnosis was 413/mm3 (range 158 to 1358); 5 of 37 patients receiving antithymocyte induction had Pneumocystis carinii versus 5 of 115 patients who did not receive induction (p = 0.05). Patients were at increased risk for the development of Pneumocystis carinii if they had more than two episodes of rejection during the first year after heart transplantation (p = 0.04). All cases were successfully treated with trimethoprim/sulfamethoxazole. The incidence of Pneumocystis carinii in infant heart transplantation recipients is approximately 7% and appears most frequently in the first 6 months after the operation. Increased risk for Pneumocystis carinii may be related to early antithymocyte induction and increased episodes of rejection.

Topics: Anti-Infective Agents; Bronchoscopy; CD4 Lymphocyte Count; Follow-Up Studies; Graft Rejection; Heart Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Infant; Infant, Newborn; Pneumocystis; Pneumonia, Pneumocystis; Postoperative Complications; Prospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) is an important infection in the setting of liver transplantation. Without prophylactic measures, the incidence of PCP reached 30% in our first 10 liver transplant patients. All patients but one, who had concomitant invasive aspergillosis, recovered with intravenous cotrimoxazole. We therefore prospectively studied, in an open clinical trial, the efficacy and safety of prophylaxis with daily low-dose cotrimoxazole (480 mg) in 60 patients. The incidence of PCP dramatically decreased to 1.7% (P<.01). Treatment was well tolerated, and discontinuation of therapy was only necessary in two patients with leukopenia. Nevertheless, the number of episodes of leukopenia was similar in both groups. Cotrimoxazole prophylaxis was not associated with increased nephrotoxicity. An overall benefit in the incidence of bacterial infection was not observed. We conclude that daily low-dose cotrimoxazole is effective and safe for prevention of PCP after liver transplantations.

Topics: Adult; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Liver Transplantation; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To establish whether an outpatient, 2-day oral desensitization protocol would be both safe and effective in HIV-infected patients with previous trimethoprim-sulfamethoxazole (TMP-SMX) intolerance.. A single center trial of TMP-SMX desensitization in HIV-infected patients with prior TMP-SMX hypersensitivity reactions.. HIV-infected patients with CD4 lymphocyte counts < 250 x 10(6)/l cells or CD4% < 20% with previous non-life-threatening hypersensitivity reactions to TMP-SMX were eligible. The desensitization protocol utilized 40 graduated doses over 36 h; the first 28 doses (7.5 h) of the protocol were given in an outpatient clinic with the remaining doses taken at home.. Twenty-seven (60%) of the 45 subjects completed the protocol and were subsequently maintained on daily TMP-SMX without adverse reactions (mean follow-up, 9 months; range, 4-16 months). Patients with CD4 counts < 100 x 10(6)/l cells were just as likely as patients with higher CD4 counts to tolerate the desensitization. No patient required hospitalization for treatment of an adverse reaction.. Oral desensitization to TMP-SMX in HIV-infected patients is a useful option in the management of patients with advanced HIV disease and prior intolerance to TMP-SMX.

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; CD4-Positive T-Lymphocytes; Drug Hypersensitivity; Drug Tolerance; Humans; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia remains one of the most common opportunistic infections in patients with acquired immune deficiency syndrome (AIDS). Treatment with either intravenous pentamidine or trimethoprim-sulfamethoxazole (TMP-SMX) is frequently complicated by serious adverse reactions. This study was a prospective, blinded comparison of 600 mg/d of pentamidine as an aerosol versus 15 mg/kg/d of trimethoprim plus 75 mg/kg/d of sulfamethoxazole for patients with mild or moderately severe P. carinii pneumonia (alveolar arterial oxygen difference of less than 55 mm Hg). Of 367 participants who were randomized to receive study therapies, 287 had proven and 16 had presumed Pneumocystis pneumonia. There were 29 deaths within 35 d of study initiation: 12 in the aerosolized pentamidine group and 17 in the TMP-SMX groups (log rank p = 0.28). The difference in mortality was 3.4% (95% CI = -3.5, 10.8%). Ninety-four patients treated with aerosolized pentamidine had to have their study therapy changed because of lack of efficacy, compared with 22 patients treated with TMP-SMX (p = 0.002). In addition PaO2 improved faster in patients treated with TMP-SMX. However, aerosolized pentamidine was discontinued less often than TMP-SMX because of toxicity (9.4 versus 40% p < 0.001). Rash (0.6 versus 14.9%), nausea and vomiting (1.7 versus 12.2%), and abnormalities of liver function tests (1.7 versus 12.2%) were the most common adverse effects necessitating treatment discontinuation. During 6-mo. follow-up there was no difference in mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; AIDS-Related Opportunistic Infections; Double-Blind Method; Female; Humans; Male; Oxygen; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Survival Analysis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the efficacy and safety of two oral, intermittent drug regimens for the simultaneous primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmosis in patients with HIV infection.. Nonblinded randomized study: Patients received either 1) trimethoprim-sulfamethoxazole (160 mg-800 mg orally twice a day on a thrice weekly regimen) or 2) 100 mg of dapsone plus 50 mg of pyrimethamine orally twice weekly.. University teaching hospital in Barcelona.. 230 patients infected with HIV who had CD4 cell counts of less than 200 x 10(6)/L and who had not previously had P. carinii pneumonia or toxoplasmosis.. Clinical and biological evaluations; adverse reactions; and end points of P. carinii pneumonia, toxoplasmosis, and death.. After a median follow-up of 430 days, 6 (6.3%) of 96 evaluable patients receiving dapsone-pyrimethamine and 0 of 104 evaluable patients receiving trimethoprim-sulfamethoxazole developed P. carinii pneumonia (P < 0.0001). The cumulative rates of P. carinii pneumonia at 12 and 24 months were 0% and 0% for patients receiving trimethoprim-sulfamethoxazole and 4% and 11% for patients receiving dapsone-pyrimethamine (Mantel-Cox, P = 0.014). However, only one episode of P. carinii pneumonia developed while patients were taking these drugs. No differences were observed for toxoplasmosis (one episode in the trimethoprim-sulfamethoxazole arm and two in the dapsone-pyrimethamine arm), with cumulative rates at 12 and 24 months of 0% and 4% for the trimethoprim-sulfamethoxazole arm and 2% and 7% for the dapsone-pyrimethamine arm (P = 0.65). Similar mortality rates were observed during follow-up (P = 0.85). Nineteen patients (9.5%) discontinued therapy with the drugs because of adverse effects: Ten were in the trimethoprim-sulfamethoxazole arm and 9 were in the dapsone-pyrimethamine arm (P = 0.95).. Thrice-weekly trimethoprim-sulfamethoxazole is an effective and well-tolerated regimen for the simultaneous primary prophylaxis of P. carinii pneumonia and toxoplasmosis in patients infected with HIV. Twice-weekly dapsone-pyrimethamine appears to be a safe and effective alternative.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasmosis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Atovaquone was compared to trimethoprim-sulfamethoxazole (TMP-SMZ) for the relationship of time receiving therapy, plasma drug concentrations, and incidence of adverse reactions in patients with AIDS-associated Pneumocystis carinii pneumonia. Treatment-limiting adverse events occurred in 9% of atovaquone-treated patients and 24% of TMP-SMZ-treated patients. Adverse events usually did not occur before day 7 for either treatment. Only the incidence of rash increased with increasing plasma concentrations of atovaquone. The incidence of anemia, neutropenia, and azotemia increased with increasing trimethoprim plasma concentration, while other adverse events (gastrointestinal disorders, rash, fever, and liver function abnormalities) were independent of plasma drug concentration.

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Double-Blind Method; Female; Humans; Male; Middle Aged; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Desensitization, Immunologic; Drug Eruptions; Drug Tolerance; HIV Infections; Homeopathy; Humans; Pneumonia, Pneumocystis; Prospective Studies; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) is the preferred agent for prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients with HIV infection, but frequent adverse events limit its usefulness. Intermittent dosing and supplementation with leucovorin have been tried in attempts to improve tolerance. We evaluated these strategies in persons with advanced HIV disease.. One hundred seven patients were enrolled. All had HIV infection, < 200 CD4+ lymphocytes per mm3, and no history of PCP. Fifty-two were randomized to TMP/SMX twice daily (BID); of these, 26 were randomized to leucovorin with each dose. Fifty-five patients were randomized to TMP/SMX (BID) 3 times per week; of these, 27 were randomized to leucovorin with each dose. All patients took zidovudine concurrently.. The 24-week risk of discontinuation due to protocol-defined limiting toxicity was 24% with thrice-weekly TMP/SMX versus 42% with daily TMP/SMX (risk ratio 0.4; 95% CI 0.2 to 1.0). The risks of discontinuation for any reason were 41% and 59% (risk ratio 0.4; 95% CI 0.2 to 0.8). Clinical toxicity, such as headache and gastrointestinal distress, accounted for the observed difference in tolerance between dosing regimens. The 24-week risk of discontinuation due to protocol-defined toxicity was 33% in both the leucovorin and non-leucovorin groups (risk ratio 1.1; 95% CI 0.5 to 2.5). The risks of discontinuation for any reason were 53% and 47% (risk ratio 0.8; 95% CI 0.3 to 1.7).. Intermittent therapy with TMP/SMX BID thrice weekly is better tolerated than daily BID therapy. Leucovorin use does not improve tolerance for chronic TMP/SMX dosing in AIDS, even among patients taking tablets daily.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Bone Marrow Diseases; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; Humans; Leucovorin; Male; Pneumonia, Pneumocystis; Proportional Hazards Models; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

We evaluated the effectiveness of three treatment strategies for the prevention of a first episode of Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus (HIV).. In an open-label trial, 843 patients with HIV infection and fewer than 200 CD4+ cells per cubic millimeter received zidovudine plus one of three randomly assigned prophylactic agents, beginning with trimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine and followed by a defined sequence of other drugs to be used in cases of intolerance.. The estimated 36-month cumulative risks of P. carinii pneumonia were 18 percent, 17 percent, and 21 percent in the trimethoprim-sulfamethoxazole, dapsone, and aerosolized-pentamidine groups, respectively (P = 0.22). The difference in risk among treatment strategies was negligible in patients entering the study with 100 or more CD4+ lymphocytes per cubic millimeter. In those entering with fewer than 100 CD4+ cells per cubic millimeter, the risk was 33 percent with aerosolized pentamidine, as compared with 19 percent with trimethoprim-sulfamethoxazole and 22 percent with dapsone (P = 0.04). The lowest failure rates occurred in patients receiving trimethoprim-sulfamethoxazole, and failures were more common with 50 mg of dapsone than with 100 mg. Toxoplasmosis developed in less than 3 percent of patients. Of the patients assigned to the two systemic therapies, only 23 percent were receiving their assigned drug and dose when they completed the study. The median survival was approximately 39 months in all three groups, and the mortality attributable to P. carinii pneumonia was only 1 percent.. In patients with advanced HIV infection, the three treatment strategies we examined have similar effectiveness in preventing P. carinii pneumonia. Strategies that start with trimethoprim-sulfamethoxazole or with high-dose dapsone, rather than aerosolized pentamidine, are superior in patients with fewer than 100 CD4+ lymphocytes per cubic millimeter.

Topics: Administration, Oral; Adult; Aerosols; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Dapsone; Drug Tolerance; Female; Humans; Male; Patient Compliance; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

At the start of the AIDS epidemic, the only agents licensed for treatment of Pneumocystis carinii pneumonia (PCP) were trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine. Both are effective against PCP, but their use has been compromised by adverse reactions that necessitate discontinuing therapy in < or = 54% of patients. As a result of the limitations in the use of these therapies, research efforts have been directed toward the development of effective agents with an improved safety profile. Of these agents, one of the best studied is atovaquone, a hydroxynaphthoquinone that has been licensed by the U.S. Food and Drug Administration for use in the treatment of mild to moderate PCP in patients intolerant to TMP-SMX. Clinical studies have shown that atovaquone is associated with overall therapeutic success rates equivalent to those of intravenous pentamidine and TMP-SMX, although its therapeutic efficacy rates are somewhat lower. However, atovaquone is associated with fewer treatment-limiting side effects than the other drugs. The literature concerning the efficacy and safety of atovaquone for the treatment of PCP will be reviewed.

Topics: AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Antiprotozoal Agents; Atovaquone; Cohort Studies; Humans; Male; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Rats; Tablets; Trimethoprim, Sulfamethoxazole Drug Combination

Thymopentin, 50 mg subcutaneously (s.c.) 3 times per week, was evaluated in a double-blind, randomized, placebo-controlled trial of zidovudine (AZT)-treated asymptomatic human immunodeficiency virus (HIV)-infected subjects with 200-500 CD4 cells/mm3 at entry. The 352 subjects were prestratified by prior AZT use into stratum I (235 subjects, > 6 months AZT at entry) and stratum II (117 subjects, < or = 6 months AZT at entry). Clinical end points, CD4 cell counts, serum p24, serum immune complex dissociated (ICD) p24, and safety variables were evaluated through 48 weeks, using an intent-to-treat analysis. The two strata were analyzed individually because they yielded different clinical outcomes, with a statistically significant treatment-by-stratum interaction. In stratum I (mean, 16 months AZT at entry) two AIDS or death events occurred in thymopentin and 10 in placebo recipients (p = 0.024; relative risk (RR) estimate, 4.9 [95% confidence limit (CI), 1.1 to 22.2]). There were three AIDS-related complex (ARC), AIDS, or death events in thymopentin and 18 in placebo recipients [p = 0.001; RR estimate, 5.9 (95% CI, 1.7 to 20.0)]. In stratum II (mean, 3 months AZT at entry), four AIDS or death events occurred in thymopentin and none in placebo recipients (p = 0.11), and four ARC, AIDS, or death events occurred in thymopentin and two in placebo recipients (p = 0.79). The treatment groups did not differ significantly with respect to changes in CD4 counts or p24 antigen levels or with respect to clinical adverse experiences or laboratory abnormalities. Thus, AZT-experienced placebo-treated subjects had relatively high progression rates to AIDS or death and to ARC, AIDS, or death, and these rates were reduced by thymopentin treatment. In contrast, placebo-treated subjects with little prior AZT experience had low progression rates; these were not significantly changed by thymopentin treatment. There was no increase in the incidence of adverse reactions with thymopentin.

Topics: Adult; CD4 Lymphocyte Count; Disease Progression; Double-Blind Method; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Follow-Up Studies; HIV; HIV Core Protein p24; HIV Infections; Humans; Injections, Subcutaneous; Male; Middle Aged; Patient Compliance; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Proportional Hazards Models; Thymopentin; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

A multicenter placebo-controlled trial of early short-term high-dose methylprednisolone enrolled 78 patients with moderate to severe Pneumocystis carinii pneumonia (PCP) complicating HIV infection. The mean pressure of oxygen (PO2) at study entry was 55 mm Hg for the 71 patients who had blood gases monitored while breathing room air. Patients were randomized to receive methylprednisolone (40 mg) or placebo parenterally twice daily for 10 days, and the first dose of study medication was given within 24 h of the first dose of antimicrobial therapy for PCP. The primary end point included death, need for mechanical ventilation for > 6 days, or a partial PO2 < 70 mm Hg while breathing room air 10 days after initiation of treatment. There was no statistically significant difference in the primary end point between patients randomized to corticosteroid (CS) or placebo (PL) (p = 0.522; 95% CI = -0.30, 0.16). The incidence of superinfections during therapy or of other HIV-associated infections or malignancies in the 6 months following treatment for PCP was not significantly different between the two groups. More patients randomized to placebo had to discontinue treatment with trimethoprim-sulfamethoxazole because of hypersensitivity than those randomized to corticosteroids (p = 0.039). We conclude that addition of corticosteroids does not significantly affect the outcome of PCP in patients with HIV and a PO2 < 70 mm Hg on room air at presentation but lowers the incidence of hypersensitivity reactions to trimethoprim-sulfamethoxazole.

Topics: Adult; AIDS-Related Opportunistic Infections; Chemotherapy, Adjuvant; Double-Blind Method; Drug Hypersensitivity; Female; HIV Infections; Humans; Male; Methylprednisolone; Pneumonia, Pneumocystis; Respiratory Function Tests; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

In a prospective, randomized open-label trial, the efficacy of sulfamethoxazole-trimethoprim (SMX-TMP) 400/80 mg b.i.d. was compared with the efficacy of aerosolized pentamidine (AP) 60 mg every 2nd week as secondary prophylaxis (SP) against recurrence of Pneumocystis carinii pneumonia (PCP) in AIDS patients. 94 patients participated in the study, 47 in each group. The patients were observed for a mean period of 17.2 months. PCP recurred in the AP group in 8 cases, while 1 relapse occurred in the SMX-TMP group. The one-year cumulative relapse rate was 9.0% (95% CI 0-19%) in the AP group compared with 2.4% (95% CI 0-8%) in the SMX-TMP group (p < 0.05). The odds ratio was 4.2 (95% CI 0.5-39.8) in favour of SMX-TMP. Furthermore, we found a tendency towards a protective effect against toxoplasmosis in the SMX-TMP group, though there was no difference in survival between the two groups. There was no statistical difference in frequency of crossover from one therapy form to the other. Based on these data we recommend SMX-TMP for secondary PCP prophylaxis.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aerosols; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pentamidine; Pneumonia, Pneumocystis; Premedication; Prospective Studies; Recurrence; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

The purpose of this prospective randomized open trial was to investigate the impact of monitoring concentrations in serum on the efficacy and side effects of high-dose co-trimoxazole therapy. Forty consecutive patients with microscopically confirmed Pneumocystis carinii pneumonia were enrolled. Therapy was started with 5 and 25 mg of trimethoprim and sulfamethoxazole, respectively, per kg of body weight given every 6 h for 2 days and continued every 8 h either with (group A) or without (group B) monitoring and dose adjustments according to sulfamethoxazole levels in serum (target, 150 to 200 micrograms/ml) for a total of 21 days. Only 7 of 19 patients (83%). Patients who were treated for the full period and patients for whom co-trimoxazole was prematurely stopped had similar concentrations of sulfamethoxazole (157 +/- 52 versus 155 +/- 47 micrograms/ml) and trimethoprim (5.0 +/- 1.4 versus 5.6 +/- 1.0 microgram/ml). Concentrations of sulfamethoxazole and trimethoprim in group A (158 +/- 39 and 5.6 +/- 1.8 micrograms/ml, respectively) did not differ from those in group B (153 +/- 57 and 5.1 +/- 1.6 micrograms/ml, respectively), and the average daily maintenance doses for groups A (75.4 mg/kg plus 15.1 mg/kg) and B (76.4 mg/kg plus 15.3 mg/kg) were nearly identical. Although the average sulfamethoxazole concentrations were maintained within the target zone in the monitoring group (day 5, 160 +/- 44 micrograms/ml; day 10, 160 +/- 41 micrograms/ml; day 15, 168 +/- micrograms/ml; and day 21, 157 +/- 95 micrograms/ml), only 28% of the individual sulfamethoxazole levels were within the target range of 150 to 200 micrograms/ml after the dose adjustments (32% in group B without intervention). Response rates were similar in both groups. Complete response or improvement was observed in 18 of 19 (group A) and 19 of 21 (group B) patients. The method used for monitoring sulfamethoxazole levels with subsequent dose adjustment did not allow us to reliably achieve the target concentrations and did not significantly alter the incidence of side effects or the efficacy of the therapy.

Topics: Adolescent; Adult; AIDS-Related Complex; AIDS-Related Opportunistic Infections; Antifungal Agents; Female; Humans; Male; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the efficacy and safety of three regimens for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) and to evaluate their effect on survival in patients with HIV infection.. Randomized, open label, prospective trial.. A single Infectious Diseases Department in Italy.. HIV-infected patients (n = 197) with a CD4 count < 200 x 10(6)/l and without previous PCP or TE.. Patients were randomly assigned to receive (1) aerosolized pentamidine (AP; 300 mg monthly), (2) cotrimoxazole (CTX; 160 mg trimethoprim and 800 mg sulfamethoxazole every other day), or (3) dapsone-pyrimethamine (DP; 100 mg weekly dapsone and 25 mg biweekly pyrimethamine).. PCP, TE, death, and drug-limiting toxicity. Considering difference in PCP occurrence the trial was interrupted on June 1992. Observation was prolonged until June 1994 for TE and survival.. Intention-to-treat analysis yielded PCP rates of 10.2 per 100 person-years in the AP, 2.0 in the CTX, and 32.1 in the DP group [adjusted relative risk of DP versus CTX: 17.5; 95% confidence interval (CI), 2.2-139.6; P = 0.007]. TE rates in patients with positive Toxoplasma serology were 25.6 per 100 person-years in the AP, 8.9 in the CTX and 9.4 in the DP group. In 'on treatment' analysis, no episode of TE developed in the DP group, and rates were 34.7 per 100 person-years in the AP and 2.5 in the CTX group (AP versus CTX: P = 0.01; AP versus DP: P = 0.004). The adjusted risk of mortality for the DP group was 2.8 times that of the CTX group in the first part of the study (95% CI, 1.1-7.3; P = 0.037), and 1.8 times (95% CI, 1.1-2.9; P = 0.02) in the prolonged follow-up. No significant difference in the occurrence of serious adverse reactions was observed between the three treatment groups.. Intermittent CTX was more effective than low-dose DP and showed a slight but not significant advantage on AP for primary PCP prophylaxis. DP was associated with a shorter survival. Both CTX and DP resulted in a significant reduction in the risk of TE.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Dapsone; Encephalitis; Female; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Ninety-two AIDS patients with Pneumocystis carinii pneumonia (PCP) were randomized to receive folinic acid or matching placebo in conjunction with trimethoprim-sulfamethoxazole in a prospective, double-blind trial. Neither frequency of dose-limiting toxicity (26% vs. 37%; P = .4) nor time to occurrence (P = .7) was associated with folinic acid use. Although incidence of neutropenia was lower in patients receiving folinic acid (23% vs. 47%; P = .03), time to occurrence of neutropenia did not differ (P = .4). Seven (7.6%) of 92 patients with confirmed PCP met criteria for therapeutic failure, and 5 (6%) died during therapy. Surprisingly, folinic acid use was associated with a higher rate of both therapeutic failure (15% vs. 0; P = .01) and death (11% vs. 0; P = .06). Time to therapeutic failure was shorter and probability of death greater in patients receiving folinic acid (P = .005, P = .02, respectively), even when adjusted for baseline arterial oxygen pressure, serum lactate dehydrogenase, respiratory rate, CD4 cell count, and peak serum level of trimethoprim or sulfamethoxazole.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Female; Humans; Incidence; Leucovorin; Male; Middle Aged; Neutropenia; Placebos; Pneumonia, Pneumocystis; Probability; Risk Factors; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

We retrospectively studied all courses of treatment with trimethoprim-sulfamethoxazole (TMP-SMZ) alone and with adjuvant corticosteroids for AIDS-associated Pneumocystis carinii pneumonia. The corticosteroids were administered for 8-21 days (mean, 14 days) because of hypoxemia. We evaluated the influence of corticosteroids on the incidence of cutaneous adverse reactions to TMP-SMZ and on the course of AIDS during 3 months of follow-up. Of 38 patients treated with TMP-SMZ alone, 18 (47%) developed cutaneous side effects, whereas three (13%) of the 23 patients who received adjuvant corticosteroid therapy experienced such effects (P = .014). Of the 21 reactive patients, 14 were treated throughout the duration of hypersensitivity. Therapy was interrupted for seven patients (18%) treated with TMP-SMZ alone and for none of those who were given adjuvant corticosteroid therapy (P = .23). During follow-up, the incidence of mucocutaneous herpes simplex virus infection was higher among patients who received adjuvant corticosteroids than among those treated with TMP-SMZ alone (P = .005). Adjuvant corticosteroids thus reduce the incidence of adverse cutaneous reactions to TMP-SMZ in patients with AIDS who are treated for hypoxemic P. carinii pneumonia.

Topics: Adrenal Cortex Hormones; Adult; AIDS-Related Opportunistic Infections; Drug Eruptions; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Dapsone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Sulfalene; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We measured the urine concentrations of sulfamethoxazole, sulfamethoxazole hydroxylamine, and N-sulfamethoxazole on days 3 and 10 in 15 patients with acquired immunodeficiency syndrome treated with a combination product of trimethoprim (15 mg/kg/day) and sulfamethoxazole (75 mg/kg/day). The percentage of sulfamethoxazole and metabolites excreted on days 3 and 10, respectively, were sulfamethoxazole 17.2% +/- 11.3% versus 15.6% +/- 8.2%; sulfamethoxazole hydroxylamine 2.6% +/- 2.0% versus 5.0% +/- 5.2% (p < 0.05); N-acetylsulfamethoxazole 80.0% +/- 12.9% versus 79.8% +/- 11.8%. The percentage of sulfamethoxazole hydroxylamine excreted was similar between the eight patients who discontinued therapy because of toxicity and the seven patients who did not (2.9% +/- 2.3% versus 2.3% +/- 2.0%, p = 0.7). In two patients who had major liver toxicity the percentage of sulfamethoxazole hydroxylamine excreted was significantly lower than that of the 13 patients who did not (0.8% +/- 0.1% versus 2.9% +/- 2.0%, p < 0.05). This is the first report of the formation and excretion of sulfamethoxazole hydroxylamine in patients with acquired immunodeficiency syndrome. With 15 patients we were unable to show a significant correlation between the percentage of sulfamethoxazole hydroxylamine excreted and adverse reactions. However, patients with liver toxicity excreted less sulfamethoxazole hydroxylamine.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Leucovorin; Male; Middle Aged; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

After completion of a placebo-controlled trial of intravenous immunoglobulin (IVIG) infection prophylaxis, patients were offered open label IVIG and optional participation in a follow-up study. The purpose of the follow-up study was to evaluate the IVIG effect in original placebo recipients and longevity of IVIG benefit in original IVIG recipients. Of 212 human immunodeficiency virus-infected children on study at trial closure, 148 (67 of 98 (68%) placebo and 81 of 114 (71%) IVIG patients) received open label IVIG for a mean of 16 months. When open label IVIG was begun, 45% were receiving trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia (43% of placebo and 47% of IVIG patients) and 54% were receiving zidovudine (55% of placebo and 53% of IVIG patients). In patients who received placebo during the original study, the rate of serious bacterial infections was significantly lower after change to open label IVIG (estimated 15.8 fewer episodes/100 patient years; 95% confidence interval, 3.2 to 28.5; P = 0.014). Similar findings were observed for minor bacterial infections (estimated 61.2 fewer/100 patient years; 95% confidence interval, 29.2 to 93.3; P < 0.001) and hospitalizations (estimated 43.7 fewer/100 patient years; 95% confidence interval, 27.7 to 59.6; P < 0.001). Decreases were observed whether or not trimethoprim-sulfamethoxazole prophylaxis was being given at the time open label IVIG was begun. In patients who received IVIG during the original study, no significant difference was seen in infections or hospitalizations after change to open label IVIG.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: AIDS-Related Opportunistic Infections; Bacterial Infections; Child; Child, Preschool; Double-Blind Method; Female; Follow-Up Studies; HIV Infections; Hospitalization; Humans; Immunoglobulins, Intravenous; Male; Pneumonia, Pneumocystis; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Female; Follow-Up Studies; HIV Infections; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Survival Rate; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We report our experience replacing trimethoprim-sulfamethoxazole (TMP/SMX) with aerosolized pentamidine (AP) in 22 children with acute leukemia who could not tolerate TMP/SMX.. Children (age 1 to 15 years) with acute leukemia during maintenance chemotherapy or post-bone marrow transplantation (BMT) receiving prophylaxis for Pneumocystis carinii pneumonia (PCP) with TMP/SMX received AP following prolonged neutropenia or allergy to TMP/SMX. Patients received 300 mg of AP monthly (children < 4 years received 150 mg) dissolved in 5 mL of distilled water over 20 to 30 minutes.. Over a 3-year period, 358 courses of AP were administered over 10,124 observable days. AP was adequately tolerated on a monthly basis for prophylaxis against PCP in 22 children with acute leukemia. AP was demonstrated to be effective in preventing PCP. There were minimal side effects observed during this trial. The majority of children with acute lymphoblastic leukemia (ALL; 12 of 14 [86%]) undergoing maintenance chemotherapy were able to resume full-dose therapy.. AP in children is well tolerated and shows high efficacy for PCP prophylaxis in children with leukemia. We conclude that AP should be considered as second-line PCP prophylactic therapy for children with acute leukemia in instances in which TMP/SMX cannot be tolerated. Phase III trials are required to determine its effect on dose intensification and event-free survival.

Topics: Administration, Inhalation; Adolescent; Aerosols; Child; Child, Preschool; Humans; Immunosuppressive Agents; Infant; Leukemia, Myeloid, Acute; Pentamidine; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Humans; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

In order to evaluate the usefulness of the polymerase chain reaction (PCR) for diagnosis and monitoring of Pneumocystis carinii pneumonia (PCP) in specimens obtained from non-invasive techniques, expectorated or induced sputa were collected from 30 patients who were tentatively diagnosed as having PCP and administered intravenous trimethoprim-sulfamethoxazole. Using appropriate criteria, 13 of these cases were diagnosed as having PCP, 12 cases were diagnosed of other pulmonary diseases, and five cases were omitted from the study according to the exclusion criteria. PCR was performed using primers based on the P. carinii 5S rRNA sequence. Pneumocystis carinii was detected in nine of the 13 defined cases (sensitivity of 69%) and in none of 12 non-PCP cases (specificity of 100%). In contrast, P. carinii was detected in only one case by microscopic examination using Diff-Quik stain. Therefore, the sensitivity of PCR was significantly higher than that observed with the stain (P < 0.05, chi 2 = 6.125). Sputum samples were also obtained from eight cases during the treatment. The eradication of P. carinii from the sputum as judged by PCR varied from three to 38 days (median 6.5 days) after the start of the treatment. Pneumocystis carinii shedding in sputum correlated with the time between initial clinical symptoms and initiation of the treatment (P < 0.05, r = 0.810), but not with the tension of PaO2 at the time of diagnosis. This preliminary study demonstrates that PCR allows early diagnosis of PCR and that close monitoring with non-invasive specimens can be performed by PCR.

Topics: Adrenal Cortex Hormones; Base Sequence; Diagnosis, Differential; DNA Primers; DNA, Fungal; DNA, Ribosomal; Evaluation Studies as Topic; Humans; Lung Diseases; Molecular Sequence Data; Oxygen; Partial Pressure; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Predictive Value of Tests; RNA, Ribosomal, 5S; Sensitivity and Specificity; Sputum; Staining and Labeling; Trimethoprim, Sulfamethoxazole Drug Combination

The effectiveness and tolerability of Sulfamethoxazole with Trimethoprim (SMX-TMP), a dose of 400mg/80mg given twice a day as secondary prophylaxis (SP) against Pneumocystis carinii pneumonia (PCP) was assessed retrospectively in 166 AIDS patients. The mean observation period was 9.7 months (range 1.0-1.4). Relapse of PCP occurred in eight patients; four episodes were histologically verified and four episodes were clinically assumed. The relapse rate after one year of prophylaxis was 5.1% (95% CI 0.0%-11.0%) using the log-rank test. Intolerance of secondary prophylaxis, defined as adverse effects necessitating cessation of SP with SMX-TMP, was reported in eight patients (5%) (95% CI 2.1%-9.3%).

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Inflammation may play a central role in the pathogenesis of HIV-related Pneumocystis carinii pneumonia (PCP). Serum levels of the amino-terminal propeptide of Type III procollagen (PIIINP) reflect inflammatory activity in granulation tissue and in chronic rheumatic and liver disorders. To investigate changes in PIIINP serum levels during an episode of HIV-related PCP, consecutive serum samples were taken from 48 HIV-infected patients with PCP in a randomized, placebo-controlled study of the effect of adjunctive methylprednisolone therapy (26 in corticosteroid [CS] group and 22 in control group). All patients were treated with co-trimoxazole. In the control group, PIIINP serum levels at day of initiation of therapy (Day 0) were significantly higher in patients requiring mechanical ventilation and/or dying during the course of the pneumonia, and serum levels of PIIINP higher than 5 ng/ml were associated with a higher mortality than levels below 5 ng/ml. The level of PIIINP increased from Day 0 to Day 5. There was a significant correlation between changes in PIIINP levels and changes in the alveolar-arterial oxygen gradient from Day 0 to Day 5. In the CS group, the PIIINP levels decreased while steroid was administered. At Days 21 to 28 there were no difference in the levels of PIIINP between the two groups. PIIINP serum levels may predict the clinical outcome of PCP. The antimicrobial therapy may exacerbate the inflammatory reaction in HIV-related PCP, leading to respiratory failure. CS prevents this increased inflammatory activity.

Topics: Adult; AIDS-Related Opportunistic Infections; Humans; Methylprednisolone; Middle Aged; Peptide Fragments; Pneumonia, Pneumocystis; Procollagen; Prognosis; Pulmonary Gas Exchange; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) continues to cause significant morbidity in recipients of solid-organ transplants. While some programs administer trimethoprim-sulfamethoxazole (TMP-SMX) prophylactically following transplantation, a prospective determination of the safety and efficacy of TMP-SMX in cardiac transplant recipients has not previously been reported. We therefore prospectively randomized 58 cardiac transplant recipients to receive TMP (160 mg)-SMX (800 mg) twice daily either three days per week (group B), or seven days per week (group C), or to receive no treatment (group A). Treatment began 14 days after transplantation and continued for four months. Age, sex, preexisting pulmonary pathology and immunosuppressive protocols did not differ among the groups. Of 17 patients in the control group (A), 7 developed a clinical syndrome compatible with PCP, with the diagnosis histologically confirmed by bronchoalveolar lavage during the first four months following transplantation. In contrast, no patients in either the daily or intermittent therapy groups developed PCP during the study period (P < 0.005). Both doses of TMP-SMX were well tolerated, and discontinuation of therapy was not necessary in any patient. Total white blood cell count, azathioprine dose, and number of treated episodes of rejection per patient did not differ among the three groups. We conclude that TMP-SMX can safely and effectively be administered to prevent the occurrence of P carinii pneumonia during the first four months following cardiac transplantation.

Topics: Adult; Drug Administration Schedule; Female; Follow-Up Studies; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Prospective Studies; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this double-blind pilot trial was to compare clindamycin/primaquine with trimethoprim-sulfamethoxazole (TMP-SMZ) as primary treatment for AIDS-related Pneumocystis carinii pneumonia (PCP). The focus was on toxicity and tolerability since comparisons of efficacy were limited by the small sample size. Sixty-five individuals with a first episode of possible PCP were randomly assigned to receive clindamycin/primaquine (34 patients) or TMP-SMZ (31 patients). PCP was subsequently proven microbiologically in 27 and 22 of the patients in these respective groups. Half of the participants had an arterial partial oxygen pressure at enrollment of < or = torr. The incidence and severity of adverse reactions were lower--but not significantly lower (P = .07 and .08, respectively)--with clindamycin/primaquine. The markers of severity improved in a similar manner regardless of which regimen was administered. No significant differences were documented in outcome, duration of survival, length of the PCP-free interval, or rate of relapse. The results of this pilot study show a trend toward less toxicity with clindamycin/primaquine than with TMP-SMZ. This result must be confirmed by larger-scale clinical trials, which are also needed to better compare the efficacy of the two regimens.

Topics: Adult; AIDS-Related Opportunistic Infections; Clindamycin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pilot Projects; Pneumonia, Pneumocystis; Primaquine; Recurrence; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the efficacy and tolerance of monthly aerosolized pentamidine versus cotrimoxazole versus dapsone plus pyrimethamine to prevent the initial episodes of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients.. An open randomized clinical trial.. HIV-infected patients (n = 331) with CD4 cell counts < 200 x 10(6)/l or with AIDS but without a history of PCP or cerebral toxoplasmosis (CT) were randomized to receive pentamidine (300 mg every 4 weeks), cotrimoxazole (160/800 mg 3 days a week) or dapsone plus pyrimethamine (100 and 25 mg weekly). If immunoglobulin G (IgG) antibodies to Toxoplasma were present, patients in the first two groups were randomized further to 25 mg pyrimethamine per week or to no treatment.. The mean follow-up was 313 days (range, 30-670 days). The three groups were homogeneous for age, sex, risk group for HIV infection, initial CD4 cell count and mean follow-up. PCP developed in 16 patients, with an estimated cumulative probability of 5.3% at 1 year of follow-up. The PCP rate per year of observation, using an intention-to-treat analysis, was 5.6% [95% confidence interval (CI), 0.9-10.3], 3% (95% CI, 0-6.3) and 8.3% (95% CI, 2.8-13.8) in the groups treated with pentamidine, cotrimoxazole and dapsone plus pyrimethamine, respectively (P > 0.05). Moderate or severe side-effects were observed in one patient on pentamidine, 10 on cotrimoxazole and nine on dapsone plus pyrimethamine (P < 0.05); the study drug had to be discontinued in no, 10 and six patients, respectively (P < 0.05). Neither cotrimoxazole alone nor pyrimethamine combined with dapsone or cotrimoxazole prevented initial episodes of toxoplasmosis among patients with IgG antibodies to Toxoplasma gondii.. Low-dose thrice-weekly cotrimoxazole or weekly dapsone plus pyrimethamine was not significantly worse (differences > 15% would have been detected with 90% certainty) than monthly aerosolized pentamidine in preventing a first episode of PCP in patients at high risk, but aerosolized pentamidine was better tolerated.

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Antifungal Agents; Dapsone; Drug Therapy, Combination; Drug Tolerance; Female; HIV Infections; Humans; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the safety and efficacy of 100 mg dapsone three times weekly for Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected, trimethoprim-sulfamethoxazole (TMP-SMX)-intolerant patients.. Retrospective chart review of patients followed-up to 22 May 1992.. Infectious diseases outpatient clinic of a tertiary care center in suburban New York City.. Twenty-three HIV-infected patients requiring PCP prophylaxis with documented intolerance to TMP-SMX.. Patients were followed clinically and with laboratory testing at approximately monthly intervals.. Dapsone was discontinued in nine (39%) patients because of adverse reactions. All reactions occurred within the first 2 months of treatment. Two (14%) of the remaining 14 patients developed histologically proven PCP over 126 patient-months of follow-up.. Approximately 40% of TMP-SMX-intolerant HIV-infected individuals are also intolerant of dapsone. Prophylaxis failures may be expected on a dose regimen of 100 mg dapsone three times weekly. More experience with other dose regimens and alternative agents is needed.

Topics: Adult; AIDS-Related Opportunistic Infections; Contraindications; Dapsone; Drug Eruptions; Female; Fever; Glutathione; HIV Infections; Humans; Leukopenia; Male; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii.. We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg).. Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of therapy in 11 patients in the atovaquone group (7 percent) and 33 patients in the trimethoprim-sulfamethoxazole group (20 percent) (P = 0.001). Therapy involving only the initial drug was successful and free of adverse effects in 62 percent of those assigned to atovaquone and 64 percent of those assigned to trimethoprim-sulfamethoxazole. Within four weeks of the completion of treatment, there were 11 deaths in the atovaquone group (4 due to P. carinii pneumonia) and 1 death in the trimethoprim-sulfamethoxazole group (P = 0.003). Diarrhea at entry was associated with lower plasma drug concentrations (P = 0.009), therapeutic failure (P < 0.001), and death (P < 0.001) in the atovaquone group but not in the trimethoprim-sulfamethoxazole group.. For the treatment of P. carinii pneumonia, atovaquone is less effective than trimethoprim-sulfamethoxazole, but it has fewer treatment-limiting adverse effects.

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Confidence Intervals; Double-Blind Method; Female; Humans; Male; Middle Aged; Naphthoquinones; Odds Ratio; Pneumonia, Pneumocystis; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the efficacy and safety of two intermittent regimens for the simultaneous primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis in HIV-infected patients.. Prospective randomized open trial.. HIV outpatient clinic of an Infectious Disease Service and a 1000-bed university teaching hospital.. A total of 166 HIV-infected patients with a CD4 cell count < 200 x 10(6)/l or a CD4 percentage < 20%, without previous PCP or toxoplasmosis.. Patients were randomized to oral (1) cotrimoxazole [160 mg trimethoprim (TMP) and 800 mg sulphamethoxazole (SMX)] twice a day on Mondays, Wednesdays and Fridays (n = 81), or (2) dapsone (100 mg) plus pyrimethamine (25 mg) (DP) once a week (n = 85).. Clinical and biological evaluation was performed every 30-60 days. End-points were PCP, toxoplasmosis and death. Adverse reactions were considered as defined in the protocol.. After a mean follow-up of 380 days, intention-to-treat analysis revealed that DP patients had a higher rate of PCP [13 out of 85 (15.2%) versus three out of 81 (3.7%); P = 0.01]. The cumulative rates of PCP at 12 and 24 months were 5 and 42% for DP patients and 3 and 10% for TMP-SMX patients, respectively (Mantel-Cox, P = 0.0007). Of the 29 patients who died during follow-up, 14 were in the TMP-SMX group and 15 in the DP group (not significant). Two patients in the TMP-SMX group and three in the DP group developed toxoplasmosis (not significant). Adverse reactions were common (66.7% of TMP-SMX patients and 42.4% of DP patients; P = 0.001). However, only 12.3% of TMP-SMX patients and 2.3% of DP patients (P = 0.01) had to discontinue therapy because of toxicity.. At the given doses, DP was inferior to TMP-SMX in preventing first episodes of PCP. Although more patients and a longer follow-up are required, the regimens appeared to prevent toxoplasmosis equally well.

Topics: Adult; AIDS-Related Opportunistic Infections; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Pyrimethamine; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Prophylaxis with low-dose trimethoprim-sulfamethoxazole has been shown to be cost-effective in the prevention of urinary tract infections, pyelonephritis, urosepsis, and pneumocystis pneumonia in renal transplant recipients. Ciprofloxacin, effective against almost all urinary tract pathogens in this patient population, represents a promising alternative prophylactic agent for patients unable to tolerate trimethoprim-sulfamethoxazole due to toxicity.. We conducted a randomized, double-blind trial to compare low-dose trimethoprim-sulfamethoxazole with ciprofloxacin for the prevention of urinary tract infections in renal transplant recipients. Patients received either ciprofloxacin (250 mg) or trimethoprim-sulfamethoxazole (80 mg trimethoprim, 400 mg sulfamethoxazole) daily for 6 months following transplantation. Treatment was considered successful if patients completed the 6-month course and 3-month follow-up period without evidence of urinary tract infection or drug-related toxicities.. Of 103 eligible patients, 51 received ciprofloxacin and 52 received trimethoprim-sulfamethoxazole. At 6 months, treatment was successful in 75% (38 of 51) receiving ciprofloxacin and 71% (37 of 52) treated with trimethoprim-sulfamethoxazole (P = 0.87, relative risk 1.04, 95% confidence limits 0.83 to 1.33). Thirteen patients (25%) receiving trimethoprim-sulfamethoxazole withdrew from the study-4 for resistant urinary tract infection and 9 for drug-related toxicity, while 3 (6%) of the patients receiving ciprofloxacin withdrew because of drug-related toxicity (P = 0.016, relative risk of urinary tract infection or adverse event 0.24, 95% confidence limits 0.07 to 0.78). At 9 months, all 38 patients who completed the 6-month course of ciprofloxacin remained free of urinary tract infection, while an additional 4 patients who had received trimethoprim-sulfamethoxazole prophylaxis (total of 8 patients over the 9 months) developed urinary tract infections (P = 0.006, Fisher's exact test for urinary tract infection alone). Pneumocystis pneumonia occurred in a total of 7 (14%) patients who were randomized to ciprofloxacin, but 2 of the 7 had withdrawn from the study at least 2 weeks prior to the diagnosis of pneumocystis pneumonia. There were no cases of pneumocystis pneumonia in patients receiving trimethoprim-sulfamethoxazole (P = 0.006). Following completion of the study, monthly aerosolized pentamidine administered in conjunction with ciprofloxacin has provided complete protection against urinary tract infection and pneumocystis pneumonia in 30 transplant recipients unable to tolerate trimethoprim-sulfamethoxazole therapy.. Ciprofloxacin is at least as effective as trimethoprim-sulfamethoxazole in the prevention of urinary tract infection in renal transplant recipients, and is better tolerated. Ciprofloxacin prophylaxis is associated with a higher incidence of pneumocystis pneumonia than is trimethoprim-sulfamethoxazole therapy. An uncontrolled follow-up study suggests that ciprofloxacin prophylaxis combined with monthly aerosolized pentamidine may be efficacious in preventing both urinary tract infection and pneumocystis pneumonia in renal transplant recipients.

Topics: Adult; Aerosols; Ciprofloxacin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Kidney Transplantation; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Postoperative Complications; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Adult; CD4-Positive T-Lymphocytes; Dapsone; Drug Administration Schedule; Female; Humans; Leukocyte Count; Male; Pneumonia, Pneumocystis; Pyrimethamine; Trimethoprim, Sulfamethoxazole Drug Combination

Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) is recommended for patients with human immunodeficiency virus (HIV) infection if their CD4 cell counts are below 200 per cubic millimeter (0.2 x 10(9) per liter). Either aerosolized pentamidine or trimethoprim-sulfamethoxazole (co-trimoxazole) is commonly prescribed for prophylaxis, but the relative efficacy and toxicity of these agents are unknown.. We conducted a multicenter trial involving 215 HIV-infected patients with no history of PCP but with CD4 cell counts below 200 per cubic millimeter. The patients were randomly assigned to one of three regimens: aerosolized pentamidine once a month, 480 mg of trimethoprim-sulfamethoxazole once a day (80 mg of trimethoprim and 400 mg of sulfamethoxazole), or 960 mg of trimethoprim-sulfamethoxazole once a day (160 mg and 800 mg, respectively). The cumulative incidence of PCP was estimated by Kaplan-Meier survival analysis.. After a mean follow-up of 264 days, 6 of the 71 patients in the pentamidine group had a confirmed first episode of PCP (11 percent), whereas none of the 142 patients in the two trimethoprim-sulfamethoxazole groups had PCP (P = 0.002). However, adverse events that required discontinuation of the medication were much more frequent in the trimethoprim-sulfamethoxazole groups (17 and 18 patients) than in the pentamidine group (2 patients). The adverse reactions occurred significantly sooner in the group given 960 mg of trimethoprim-sulfamethoxazole than in the group given 480 mg (mean time, 16 vs. 57 days; P = 0.02).. For patients with HIV infection, trimethoprim-sulfamethoxazole taken once a day is more effective as primary prophylaxis against PCP than aerosolized pentamidine administered once a month, although adverse drug reactions are more frequent with trimethoprim-sulfamethoxazole.

Topics: Adult; Aerosols; Aged; AIDS-Related Opportunistic Infections; CD4-Positive T-Lymphocytes; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Leukocyte Count; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Random Allocation; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Standard treatments of HIV-associated Pneumocystis carinii pneumonia (PCP) consist of high dose intravenous or oral cotrimoxazole or intravenous pentamidine. Both treatment modalities are associated with a high incidence of side effects which strengthen the need for alternative therapies. Since April 1987 we have used the combination of dapsone plus trimethoprim (DP+TMP) as primary treatment for PCP in patients who could be managed on an outpatient basis. We report the results of an analysis of the efficacy and toxicity of this treatment in 20 episodes of PCP in 18 patients. PCP was diagnosed by identification of the pathogens in bronchoalveolar lavage specimens. Chest X-ray revealed bilateral involvement in 11 and unilateral in 7 cases and no infiltration in one patient. Treatment over three to four weeks was successful in 14 of 20 PCPs (70%). In six cases (30%) treatment was changed to another regimen after a mean of seven days due to a maculopapular rash (n = 2), haematotoxic side effects (n = 2), persistent fever (n = 1) and for unexplained reasons (n = 1). Less severe side effects not causing a change in treatment were a slight to moderate neutropenia (n = 10), a moderate elevation of liver enzymes (n = 2) and a well tolerated rash (n = 2). The success rate of DP+TMP was in the same range as it is known for the standard regimens, whereas the rate of severe side effects appears to be lower. The results suggest that in AIDS patients DP+TMP may be used as first line treatment of PCP which is not severe enough for hospitalisation.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Ambulatory Care; Dapsone; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) continues to be the most common index diagnosis in the acquired immunodeficiency syndrome (AIDS), but it is not clear which of several available agents is the most effective in preventing a recurrence of PCP.. We conducted a comparative, open-label trial in 310 adults with AIDS who had recently recovered from an initial episode of PCP and had no treatment-limiting toxic effects of trimethoprim-sulfamethoxazole or pentamidine. All the patients were treated with zidovudine and were randomly assigned to receive either 800 mg of sulfamethoxazole and 160 mg of trimethoprim once daily or 300 mg of aerosolized pentamidine administered every four weeks by jet nebulizer. The participants were followed for a median of 17.4 months.. In the trimethoprim-sulfamethoxazole group (n = 154) there were 14 recurrences of PCP, as compared with 36 recurrences (including 1 extrapulmonary recurrence) in the aerosolized-pentamidine group (n = 156). The estimated recurrence rates at 18 months were 11.4 percent with trimethoprim-sulfamethoxazole and 27.6 percent with pentamidine (P < 0.001). The risk of a recurrence (adjusted for initial CD4 cell count) was 3.25 times higher in the pentamidine group (P < 0.001, 95 percent confidence interval, 1.72 to 6.16). There were no significant differences between the groups in survival or in hematologic or hepatic toxicity. Crossovers from trimethoprim-sulfamethoxazole to aerosolized pentamidine were more common than the reverse (27 vs. 4 percent), partly because of the study protocols for the management of leukopenia. There were 19 serious bacterial infections in the trimethoprim-sulfamethoxazole group and 38 in the pentamidine group. The time to a first bacterial infection was significantly greater for those assigned to trimethoprim-sulfamethoxazole (P = 0.017).. In patients with AIDS who are receiving zidovudine, trimethoprim-sulfamethoxazole is more effective than aerosolized pentamidine in conventional doses for the prevention of recurrent pneumocystis infection.

Topics: Aerosols; AIDS-Related Opportunistic Infections; Female; Follow-Up Studies; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Random Allocation; Recurrence; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

To compare cotrimoxazole and eflornithine as primary treatment for first-episode Pneumocystis carinii pneumonia (PCP).. Prospective open-labelled study.. Patients were randomized to eflornithine (400 mg/kg daily, as a continuous intravenous infusion) or cotrimoxazole (3.84 g twice daily, intravenously) for 14 days.. Only 39% of patients treated with eflornithine (20 out of 51) and 40% of those given cotrimoxazole (nine out of 47) successfully completed therapy. Although 12 out of the 36 patients with confirmed PCP were treated successfully with eflornithine, significantly more patients were withdrawn from the eflornithine group because of therapy failure (25 out of 51 versus 10 out of 47, P = 0.007). This significant difference persisted in patients in whom a diagnosis of PCP was confirmed histologically (19 out of 33 versus seven out of 27, P = 0.03). Significantly more patients were withdrawn from cotrimoxazole because of serious drug-related side-effects (38 versus 12%, P = 0.005).. Eflornithine (400 mg/kg daily) is less effective than cotrimoxazole (7.68 g daily) as treatment for first-episode PCP. Eflornithine does have activity against P. carinii in humans.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Chemotherapy, Adjuvant; Eflornithine; Female; Humans; Injections, Intravenous; Male; Pneumonia, Pneumocystis; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The purpose of this study was to compare the efficacy and safety of dapsone and trimethoprim/sulfamethoxazole in the primary prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients infected with the human immunodeficiency virus (HIV) and having less than 200 CD4-positive cells per ml. This was a prospective, randomized, open-label study, using dapsone (100 mg p.o.) or trimethoprim/sulfamethoxazole (160 mg/800 mg p.o.) daily. Patients who developed toxicity requiring discontinuation were offered to cross over to the other study drug. They continued in the study until development of toxicity or documented PCP. Eighty-six patients were enrolled; 47 were randomized to receive dapsone and 39 to receive trimethoprim/sulfamethoxazole. Discontinuation of initial study drug occurred in 33 of the dapsone group and 25 of the trimethoprim/sulfamethoxazole group. Rash was the most common reason for discontinuation. Ten patients crossed over from dapsone to trimethoprim/sulfamethoxazole (4 successfully) and 11 patients crossed over from trimethoprim/sulfamethoxazole to dapsone (6 successfully). During 1,638 patient-months of observation (862 for dapsone and 776 for trimethoprim/sulfamethoxazole), one episode of PCP developed in each group. Both dapsone and trimethoprim/sulfamethoxazole are efficacious for the prophylaxis of PCP in HIV-infected persons with less than 200 CD4-positive cells per ml, but are each associated with significant toxicity. Development of toxicity to one drug does not invariably predict toxicity to the other.

Topics: Adult; Dapsone; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Humans; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the clinical efficacy and safety of trimethoprim-sulfamethoxazole (TMP-SMX) with pentamidine in the therapy of Pneumocystis carinii pneumonia (PCP) in patients with AIDS.. TMP-SMX (TMP, 20 mg/kg/day plus SMX, 100 mg/kg/day) was compared with pentamidine (4 mg/kg/day), both administered intravenously for 21 days in a prospective randomized treatment trial of 163 patients diagnosed with PCP between November 1984 and May 1988.. Ninety-two evaluable patients received TMP-SMX as initial therapy; 68 received pentamidine. Failure to complete therapy was common. Of those receiving TMP-SMX, 39 (42%) required change in therapy because of failure to respond, and an additional 31 (34%) because of drug toxicity. This compared with 27 (40%; P = 0.733) and 17 (25%; P = 0.235), respectively, in the pentamidine-treated group. The overall survival rates were similar in the two groups, 62 out of 92 (67%) initially administered TMP-SMX versus 50 out of 68 (74%) initially administered pentamidine (P = 0.402). The survival rates for patients requiring a change in therapy because of failure to respond was 46% (18 out of 39) for the TMP-SMX group compared with 56% (15 out of 27) for the pentamidine group. When a change in therapy was made because of toxicity, survival rates were 97% (30 out of 31) for those receiving TMP-SMX versus 94% (16 out of 17) for those receiving pentamidine.. TMP-SMX and pentamidine are of equivalent efficacy as initial therapies for PCP in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Male; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Fifty-nine human immunodeficiency virus type-1-infected patients with a microscopically proven first episode of moderate to severe Pneumocystis carinii pneumonia (PCP) were enrolled into a randomized European multicenter study. The effect of adjunctive corticosteroid (CS) therapy was assessed on (a) survival to discharge, (b) need for mechanical ventilation, and (c) survival at day 90. CS was given within 24 h of standard therapy as intravenous methylprednisolone 2 mg/kg body weight daily for 10 days. All patients received cotrimoxazole as standard treatment. Inclusion criteria were a PaO2 less than 9.0 kPa (67.5 mm Hg) and/or a PaCO2 less than 4.0 kPa (30.0 mm Hg) while breathing room air. During the acute episode of PCP, 9 (31%) of the 29 control patients died versus 3 (10%) of the 30 CS patients; p = 0.01. Mechanical ventilation was necessary in 15 patients; 12 (41%) in the control group and 3 (10%) in the CS group; p = 0.01. The 90-day survival was 69% in controls versus 87% in CS patients; p = 0.07. Based on these data we conclude that adjunctive CS therapy for moderate to severe PCP in AIDS patients reduces the acute mortality and the need for mechanical ventilation.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Blood Gas Analysis; Drug Therapy, Combination; Europe; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Aerosols; Animals; Cryptococcosis; Cytomegalovirus Infections; Dapsone; Drug Combinations; Humans; Mycobacterium avium-intracellulare Infection; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Sulfadoxine; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Dapsone; Follow-Up Studies; Humans; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Trimethoprim, Sulfamethoxazole Drug Combination

Although used widely, the effectiveness of zidovudine therapy and primary prophylaxis for Pneumocystis carinii pneumonia (PCP) in HIV-1-infected individuals, has not been assessed in a large cohort. We have done an observational study between October, 1986, and October, 1990, of a cohort of 2145 HIV-1-seropositive men and 371 who seroconverted during the study. A Markov chain transitional analysis was used to examine the effect of zidovudine and PCP prophylaxis on the probability of progression of HIV-1 infection to AIDS (after 6, 12, 18, and 24 months) after follow-up visits categorised into one of six disease states. The six starting states were based on CD4+ lymphocyte counts and the presence of HIV-related symptoms. Use of pre-AIDS zidovudine and PCP prophylaxis was associated with significant reductions in rates of progression to AIDS at 6, 12, 18, and 24 months for participants starting with less than 350 CD4+ lymphocytes/microliter. For those starting with 350 or more CD4+ lymphocytes/microliter, non-significant protective trends were seen during 12, 18, and 24 month intervals. In multivariate log-linear models virtually all the treatment effect was due to zidovudine. However, after adjusting for the effects of zidovudine, PCP prophylaxis reduced significantly the probability of progression to a first episode of PCP during 6, 12, 18, and 24 month intervals. This study suggests that early primary PCP prophylaxis is effective in preventing first episodes of PCP, and that the efficacy of zidovudine demonstrated in clinical trials can be translated to the population level.

Topics: Acquired Immunodeficiency Syndrome; Aerosols; CD4-Positive T-Lymphocytes; Evaluation Studies as Topic; Follow-Up Studies; HIV Seropositivity; HIV-1; Humans; Leukocyte Count; Male; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Regression Analysis; Risk Factors; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Diphenhydramine; Double-Blind Method; Drug Eruptions; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Hemophiliacs infected with human immunodeficiency virus with a history of hypersensitivity reaction to a combination product of trimethoprim and sulfamethoxazole were desensitized orally. Six of the seven patients included in the study successfully completed the desensitization protocol and received trimethoprim-sulfamethoxazole for 5 to 7 months after desensitization (mean length of treatment, 5.7 months) for prophylaxis of Pneumocystis carinii pneumonia. The small number of patients and the short follow-up allow us to suggest that oral desensitization may be an effective and inexpensive means to treat hemophiliacs infected with human immunodeficiency virus with trimethoprim-sulfamethoxazole as prophylaxis against Pneumocystis carinii pneumonia.

Topics: Administration, Oral; Adolescent; Adult; AIDS-Related Opportunistic Infections; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes; Child; Desensitization, Immunologic; Drug Hypersensitivity; Female; Follow-Up Studies; Hemophilia A; HIV Infections; Humans; Leukocyte Count; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Aerosols; Humans; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

We studied 21 patients with the acquired immunodeficiency syndrome and presumed Pneumocystic carinii choroidopathy. The lesions were characteristically yellow to pale yellow in color, appeared at the level of the choroid, and were found in the posterior pole. They varied in size from 300 to 3,000 microns, initially increasing in number before treatment and eventually resolving after systemic antimicrobial therapy. Of the 21 patients, 18 (86%) had received inhaled pentamidine as prophylaxis against Pneumocystis pneumonia. Visual acuity and visual field testing showed little evidence of retinal destruction. Survival after the diagnosis of the choroidopathy ranged from two to 36 weeks. Pneumocystic choroidopathy offers an easily accessible clue to disseminated Pneumocystis infection. When comparing drugs for Pneumocystis prophylaxis, careful ocular examination can provide one indicator of the relative efficacy of protection against extrapulmonary disease.

Topics: Acquired Immunodeficiency Syndrome; Adult; Choroid Diseases; Drug Administration Routes; Eye Infections, Fungal; Female; Fluorescein Angiography; Fundus Oculi; Humans; Male; Middle Aged; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination; Visual Acuity; Visual Fields

Mild to moderately severe Pneumocystis carinii pneumonia in patients with AIDS was treated in a clinical trial with a combination regimen of primaquine and clindamycin, and the efficacy of this regimen was compared with that of the conventional treatment regimen of trimethoprim/sulfamethoxazole. The results revealed that primaquine/clindamycin appears to be an equally effective alternative to trimethoprim/sulfamethoxazole. The spectrum of side-effects was similar for the two regimens; side-effects occurred with equal frequency but appeared to be less severe in patients given primaquine/clindamycin. Because therapy with primaquine and clindamycin was limited to patients with mild to moderate Pneumocystis carinii pneumonia, studies with this regimen in more severe cases are warranted.

Topics: Acquired Immunodeficiency Syndrome; Adult; Clindamycin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

A double-blind placebo controlled trial of foscarnet was conducted in 32 Human Immunodeficiency Virus (HIV) antibody positive male homosexuals with a presumed AIDS pneumonia. The study was designed to evaluate the importance of treating cytomegalovirus (CMV) as a possible lung pathogen of these patients and as a toxicity study of foscarnet. Trial subjects were randomised to receive either foscarnet or placebo as a continuous intravenous infusion for 2 weeks along with conventional therapy against Pneumocystis carinii (PC) pneumonia. Bronchoscopy or post-mortem showed PC to be present in 24 patients and the bronchoalveolar lavage fluid had early antigen foci of CMV in nine, five of these being double infections. The incidence of CMV infection in this group of patients was not sufficiently high to prove or disprove that treatment of CMV speeds recovery or improves prognosis in AIDS pneumonias. Overall however foscarnet was well tolerated with a slight increase in adverse reactions in the treated groups. This agent is therefore a relatively non-toxic drug to use in the treatment of established CMV disease.

Topics: Acquired Immunodeficiency Syndrome; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Foscarnet; HIV Seropositivity; Humans; Infusions, Intravenous; Male; Phosphonoacetic Acid; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

In an open, prospective, randomized study we compared efficacy and side effects of 8 g/d cotrimoxazole (TMP/SMX) i.v. vs. 600 mg aerosolized pentamidine. 29 of 60 planned case record forms are now evaluated. Efficacy in both groups was comparable, but side effects in the pentamidine arm were very rare (7.2% vs. 40% in the TMP/SMX group). In moderate pneumocystis carinii pneumonia aerosolized pentamidine could be the first choice therapy. Necessary conditions are to use proper inhalation systems, experience, and the treatment of relevant accompaning bacterias, which we found in 80% of pneumocystis carinii positive bronchoalveolar lavages.

Topics: Administration, Inhalation; Adult; HIV Infections; Humans; Infusions, Intravenous; Male; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Preliminary reports suggest that patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia may benefit from the addition of corticosteroid treatment to antibiotic therapy.. We conducted a double-blind, placebo-controlled trial to assess the efficacy of adjunctive corticosteroids in patients with AIDS and severe P. carinii pneumonia. Patients with marked abnormalities in gas exchange who had been treated with antibiotics for less than 72 hours were randomly assigned to receive either methylprednisolone (40 mg) or placebo every 6 hours for 7 days, in addition to treatment for 21 days with trimethoprim-sulfamethoxazole. The primary outcome measures were survival until hospital discharge and the development of respiratory failure.. Twenty-three patients were enrolled in the study; there were no significant differences in base-line clinical or laboratory measures between the two treatment groups. Of 12 patients treated with corticosteroids, 9 (75 percent) survived until hospital discharge, as compared with only 2 of 11 placebo recipients (18 percent) (P less than 0.008). Respiratory failure developed in nine placebo recipients, as compared with only three patients treated with corticosteroids (P less than 0.008). No patient required the interruption or discontinuation of corticosteroid or antibiotic treatment because of toxicity or a complicating event. Because of the marked difference in survival, it was deemed unethical to continue the trial, and the study was terminated.. Early adjunctive corticosteroid therapy can improve survival and decrease the occurrence of respiratory failure in patients with AIDS and severe P. carinii pneumonia.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Adult; Aged; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Methylprednisolone; Middle Aged; Pneumonia, Pneumocystis; Respiratory Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination

Twenty-four cancer patients with diffuse interstitial pneumonitis (DIP) were randomized to undergo an open lung biopsy (OLB) within 8 hours of presentation (12 patients) or to receive empiric antimicrobial therapy (ET) with trimethoprim-sulfamethoxazole (TMP-SMX) erythromycin for a minimum of 4 days (12 patients). Patients whose condition deteriorated underwent an OLB on day 4. Eight of 12 patients (67%) having OLB survived versus 10 of 12 (83%) receiving ET (P = .64). Morbidity occurred in nine of 12 (75%) having OLB versus eight of 12 (67%) receiving ET (P = 1.0). Concurrently, there were 14 additional cancer patients with DIP who were not randomized (nine refused, three had a coagulopathy contraindicating surgery, two were excluded by primary care physicians) and who were comparable demographically to the randomized group. Two received OLB and 12 ET. Combining the randomized and nonrandomized groups, eight of 14 (57%) having an initial OLB survived versus 18 of 24 (75%) of ET-treated patients (P2 = .19). Results of the OLB were seven Pneumocystis carinii pneumonia (PCP), five nonspecific pneumonitis (NSP), one cytomegalovirus, and one lymphoma. Results of OLB led to discontinuation of antibiotics in three patients. Of the 24 ET patients, eight failed to improve by day 4 and had an OLB. Results were two NSP, two PCP, two cancer, one blastomycosis, and one Candida pneumonia. Complications were seen in 10 of 14 (72%) initial OLB patients versus 14 of 24 (58%) patients on the ET arm (P = .65). When the complication rate between patients receiving only empiric antibiotics was compared with all patients having an OLB (initially or on day 4), the difference was greater in patients undergoing OLB (37% v 72%, respectively) (P2 = .14). ET with TMP-SMX plus erythromycin and broad spectrum antibiotics in granulocytopenic patients appeared to be as successful and potentially less toxic than an OLB in this study. Although the number of patients in this study was small, these data suggest that a trial of empiric antibiotic management may be reasonable in cancer patients presenting with DIP, especially if they are nonneutropenic.

Topics: Adult; Agranulocytosis; Biopsy; Diagnosis, Differential; Drug Therapy, Combination; Erythromycin; Female; Humans; Male; Middle Aged; Neoplasms; Pneumonia, Pneumocystis; Prospective Studies; Pulmonary Fibrosis; Random Allocation; Trimethoprim, Sulfamethoxazole Drug Combination

Standard therapy of pneumocystis carinii pneumonia with cotrimoxazole and intravenous pentamidine second line therapy both have a response rate of 75 to 90%. As severe side effects, myelotoxicity and skin reaction have been observed which may occur from treatment day 7 on. In order to prevent such side effects as well as reduce hospitalization times, an open, randomized pilot study was designed. Object of this study was the comparison of efficacy and safety of two different treatment schemes: standard therapy versus sequential treatment. Twelve patients were treated according to study design: five patients with cotrimoxazole only, and seven patients with sequential therapy consisting of cotrimoxazole followed by pentamidine aerosol. All patients were treated for 21 days. Four out of five patients with cotrimoxazole, and two out of seven patients with sequential therapy, were successfully treated and had no pneumocystis carinii pneumonia relapses within four weeks after termination of treatment. Each group had one treatment failure. Four patients under sequential treatment were not evaluable. - In spite of the rather unfavourable preliminary results, the study should be continued. However, patients with secondary opportunistic infections respectively other severe diseases should not be included into the study.

Topics: Administration, Inhalation; Adult; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Middle Aged; Opportunistic Infections; Pentamidine; Pilot Projects; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Antimicrobial drugs that can be taken orally are needed for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Preliminary data indicate that dapsone with trimethoprim may be an effective alternative to trimethoprim-sulfamethoxazole, which is frequently toxic.. In a double-blind trial, 60 patients with AIDS and mild-to-moderately-severe first episodes of P. carinii pneumonia (partial pressure of oxygen in arterial blood, greater than 60 mm Hg while breathing room air) were randomly assigned to 21 days of treatment with either trimethoprim-sulfamethoxazole (20 and 100 mg per kilogram of body weight per day, respectively) or trimethoprim-dapsone (20 mg per kilogram per day and 100 mg per day).. The orally administered treatment failed because of progressive pneumonitis in 3 of the 30 patients assigned to trimethoprim-sulfamethoxazole and in 2 of the 30 assigned to trimethoprim-dapsone (P greater than 0.3). Major toxic effects required a switch to intravenous pentamidine for 17 patients (57 percent) in the trimethoprim-sulfamethoxazole group, as compared with 9 (30 percent) in the trimethoprim-dapsone group (P less than 0.025). With trimethoprim-sulfamethoxazole, there were more instances of severe chemical hepatitis (six, as compared with one in the trimethoprim-dapsone group) and marked neutropenia (five vs. one). Intolerable rash (three in each treatment group) and severe nausea and vomiting (two in each group) occurred with equal frequency with both drug combinations. Methemoglobinemia occurred in most of the patients treated with trimethoprim-dapsone, but it was asymptomatic and the level exceeded 20 percent in only one patient. Mild hyperkalemia (serum potassium level, 5.1 to 6.1 mmol per liter) also occurred in 53 percent of the patients treated with trimethoprim-dapsone.. In patients with AIDS, oral therapy with trimethoprim-sulfamethoxazole and with trimethoprim-dapsone are equally effective for mild-to-moderate first episodes of P. carinii pneumonia, but with trimethoprim-dapsone there are fewer serious adverse reactions than with trimethoprim-sulfamethoxazole.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Chemical and Drug Induced Liver Injury; Dapsone; Double-Blind Method; Drug Combinations; Female; Humans; Male; Neutropenia; Pentamidine; Pneumonia, Pneumocystis; Random Allocation; Survival Rate; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Antiprotozoal Agents; Clinical Trials as Topic; Dapsone; Drug Combinations; Humans; Pentamidine; Pneumonia, Pneumocystis; Quinazolines; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate; Zidovudine

To ascertain the efficacy and toxicity of trimethoprim-sulfamethoxazole or pentamidine when either is given alone during the entire treatment period for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS).. Prospective, randomized, noncrossover comparison of trimethoprim-sulfamethoxazole with pentamidine. Trimethoprim-sulfamethoxazole dosage was adjusted to maintain serum trimethoprim at 5 to 8 micrograms/mL. Pentamidine dosage was reduced by 30% to 50% for an absolute rise in serum creatinine of more than 88 mumol/L (1 mg/dL).. Tertiary care hospital and AIDS clinic.. Thirty-six patients were treated with trimethoprim-sulfamethoxazole and 34 with pentamidine. Pretreatment clinical features and laboratory test results were similar in the two groups.. Thirty-six recipients of trimethoprim-sulfamethoxazole and 33 recipients of pentamidine completed therapy without crossover. Trimethoprim-sulfamethoxazole caused a rash (44%) and anemia (39%) more frequently (P less than or equal to 0.03, whereas pentamidine caused nephrotoxicity (64%), hypotension (27%), or hypoglycemia (21%) more frequently (P less than or equal to 0.01). The (A - a)DO2 improved by greater than 1.3 kPa (10 mmHg) 8 days earlier for trimethoprim-sulfamethoxazole recipients (95% CI for the difference in response, -1 to 17; P = 0.04). Thirty-one (86%) patients treated with trimethoprim-sulfamethoxazole and 20 (61%) with pentamidine survived and were without respiratory support at completion of treatment (95% CI for the difference in response, 5% to 45%; P = 0.03).. For most patients with AIDS and P. carinii pneumonia, successful treatment with a single agent is possible. Toxicity associated with the two standard treatments is rarely life-threatening and may be diminished if the trimethoprim-sulfamethoxazole dosage is modified by pharmacokinetic monitoring and the pentamidine dosage is reduced for nephrotoxicity. Oxygenation improved more quickly and survival was better with trimethoprim-sulfamethoxazole.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amidines; Drug Combinations; Hematologic Diseases; Humans; Kidney Diseases; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

We conducted a prospective, randomized clinical trial over a two-year period in patients with acute lymphocytic leukemia to assess the effectiveness of trimethoprim-sulfamethoxazole given on three consecutive days each week as compared with daily in the prevention of Pneumocystis carinii pneumonitis. P. carinii pneumonitis did not develop in any of 92 patients receiving the drug daily (30,602 patient-days) or in any of 74 who received it three consecutive days a week (27,329 patient-days), whereas the incidence of the infection expected without prophylaxis is 21 percent. One patient, excluded from both groups because of an adverse reaction to sulfonamides in the past, acquired P. carinii pneumonitis. Especially noteworthy was a difference in the occurrence of systemic mycoses, with 10 cases in the daily-treatment group and only 1 case in the three-days-a-week group (P = 0.024). No differences were observed in the rates of other infections or adverse effects associated with the drug. We conclude that trimethoprim-sulfamethoxazole is as effective given three days a week as it is given daily in the prevention of P. carinii pneumonitis and that the intermittent schedule has the advantages of less frequent fungal infections and lower cost. Intermittent chemoprophylaxis may be especially beneficial to certain patients who are unable to tolerate the daily doses.

Topics: Anti-Infective Agents; Child; Child, Preschool; Drug Administration Schedule; Drug Combinations; Evaluation Studies as Topic; Female; Humans; Leukemia, Lymphoid; Male; Mycoses; Pneumonia, Pneumocystis; Prospective Studies; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Forty patients with the acquired immunodeficiency syndrome (AIDS) and their first episodes of Pneumocystis carinii pneumonia were assigned at random to receive either trimethoprim-sulfamethoxazole or pentamidine isethionate. The two groups did not differ significantly in the severity of pulmonary or systemic processes at enrollment. Five patients treated initially with trimethoprim-sulfamethoxazole and one patient treated initially with pentamidine died during the 21-day treatment period (p = 0.09, Fisher's exact test). No significant differences were seen between groups in rates of improvement, pulmonary function tests, or 67Ga uptake by the lungs in the survivors at completion of therapy. Adverse reactions necessitated changing from the initial drug in 10 patients in the trimethoprim-sulfamethoxazole group and 11 in the pentamidine group. Minor reactions occurred in all patients. In patients with AIDS, trimethoprim-sulfamethoxazole and pentamidine do not have statistically significant differences in efficacy or frequency of adverse reactions.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amidines; Clinical Trials as Topic; Drug Combinations; Dyspnea; Humans; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Random Allocation; Respiratory Function Tests; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Animals; Bronchoscopy; Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Eflornithine; Humans; Male; Ornithine; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Pyrimethamine; Sulfadiazine; Sulfamethoxazole; Therapeutic Irrigation; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Pentamidine isethionate and sulfamethoxazole-trimethoprim are effective in the treatment of Pneumocystis carinii pneumonia in the immunosuppressed pediatric patient. To compare their efficacy and toxicity, 25 pediatric cancer patients with biopsy-proved P carinii pneumonia were randomly assigned to receive either pentamidine intramuscularly or sulfamethoxazole-trimethoprim orally for 14 days. No differences in response or frequency of side effects were noted between the two drug regimens, with recovery occurring in 24 (96%) of 25 children. Skin eruptions and hematologic abnormalities were the most common side effects of sulfamethoxazole-trimethoprim therapy, while local reactions at injection sites, abnormal renal function, and hypoglycemia were the most frequent complications of pentamidine treatment. The ease of administration and less serious side effects of sulfamethoxazole-trimethoprim make it the drug of first choice for treating P carinii pneumonia. Pentamidine remains an important drug for patients who fail to respond to this initial therapy.

Topics: Acute Disease; Adolescent; Adult; Amidines; Child; Child, Preschool; Clinical Trials as Topic; Drug Combinations; Humans; Infant; Infant, Newborn; Leukemia; Male; Pentamidine; Pneumonia, Pneumocystis; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Recent studies have reported that reduced-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be effective in the treatment of Pneumocystis jirovecii pneumonia (PJP), but data are lacking for patients with hematologic malignancies.. This retrospective study included all adult hematologic patients with PJP between 2013 and 2017 at 6 Swedish university hospitals. Treatment with 7.5-15 mg TMP/kg/day (reduced dose) was compared with >15-20 mg TMP/kg/day (standard dose), after correction for renal function. The primary outcome was the change in respiratory function (Δpartial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2]) between baseline and day 8. Secondary outcomes were clinical failure and/or death at day 8 and death at day 30.. Of a total of 113 included patients, 80 patients received reduced dose and 33 patients received standard dose. The overall 30-day mortality in the whole cohort was 14%. There were no clinically relevant differences in ΔPaO2/FiO2 at day 8 between the treatment groups, either before or after controlling for potential confounders in an adjusted regression model (-13.6 mm Hg [95% confidence interval {CI}, -56.7 to 29.5 mm Hg] and -9.4 mm Hg [95% CI, -50.5 to 31.7 mm Hg], respectively). Clinical failure and/or death at day 8 and 30-day mortality did not differ significantly between the groups (18% vs 21% and 14% vs 15%, respectively). Among patients with mild to moderate pneumonia, defined as PaO2/FiO2 >200 mm Hg, all 44 patients receiving the reduced dose were alive at day 30.. In this cohort of 113 patients with hematologic malignancies, reduced-dose TMP-SMX was effective and safe for treating mild to moderate PJP.

Topics: Adult; Hematologic Neoplasms; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The effectiveness and safety of trimethoprim/sulfamethoxazole (TMP/SMX) desensitization therapy is insufficiently evaluated in hematological diseases. From 2002 to 2019, we retrospectively analyzed 112 patients with hematological diseases who underwent desensitization therapy after TMP/SMX prophylaxis withdrawal due to adverse events. They orally started TMP/SMX at 0.4 mg/2 mg, which was then increased daily to 80 mg/400 mg for 5 or 9 days. Eighty-eight patients (79%) had complete desensitization, and the major reason for failure was rash seen in 21 cases (19%). The cause of desensitization and reasons for failure matched in 22 cases (92%). Pneumocystis pneumonia was not observed throughout the study. In the failure group, the number of eosinophils and alanine aminotransferase (ALT) levels were significantly increased after desensitization. In particular in the failure group, the slight increase in eosinophils was seen through the beginning to halfway during desensitization (36/μL (0-900/μL) and 48/μL (0-2560/μL), respectively, p = 0.025). These data show that TMP/SMX desensitization therapy is effective and safe in hematological diseases. The recurrence of adverse events could help predict desensitization success.

Topics: Feasibility Studies; Hematologic Diseases; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To identify potential risk factors and prognostic factors of Pneumocystis jirovecii pneumonia (PJP) infection in anti-melanoma differentiation-associated gene 5 antibody-positive DM (anti-MDA5+ DM) patients, and to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS).. Anti-MDA5+ DM patients who underwent mNGS or real-time PCR for PJP detection were recruited. The potential risk factors for PJP occurrence and death were analysed via Logistic regression and Cox proportional hazards regression, respectively. The diagnostic efficacy of mNGS was compared with the conventional methods.. 91 patients were enrolled and 44 were assigned to PJP+ group. The PJP detection rate was 48.4%. PJP often occurred in the first 3 months (68.2%) of the disease; this period also showed the highest mortality rate (20.5%). Fever and increased lactate dehydrogenase (LDH) were independent risk factors for PJP occurrence, while trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis was an independent protective factor (all P < 0.05). Older age and increased LDH were predictors for mortality in patients with anti-MDA5+ DM and PJP (all P < 0.05). In addition, we found that mNGS had a sensitivity of 100.0% and specificity of 90.0% in diagnosing PJP, with the highest area under the curve of 0.95 (P < 0.001).. PJP has high prevalence and mortality in anti-MDA5+ DM. It is crucial for clinicians to identify high-risk patients and promptly institute TMP/SMZ to prevent PJP. mNGS is the preferred approach for pathogen detection in anti-MDA5+ DM when PJP is suspected.

Topics: Dermatomyositis; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Prevalence; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is an opportunistic infection that causes significant morbidity and mortality in the immunocompromised population. This population is growing and diversifying, yet contemporary epidemiology is lacking. We investigated the population-level incidence of PCP over the past decade.. We conducted a descriptive study of all hospital admissions in England from April 2012 to March 2022. PCP episodes, age, median length of stay, gender and episodes of other respiratory fungal infections were collected. Consumption of Trimethoprim-Sulfamethoxazole was obtained between January 2019 and May 2022.. The incidence of PCP increased from 2·2-4·5/100,000 population between 2012/2013 and 2019/2020 (p < 0·0001). There was a drop in 2020/2021 to 2·7/100,000 before returning to 3.9/100,000 in 2021/2022. PCP episodes rose as a proportion of all-cause admissions as well as a proportion of episodes due to other fungal infections. The proportion of PCP patients aged 75+ increased from 14% to 26%. The median length of stay was 13.5 days. Consumption of intravenous Trimethoprim-Sulfamethoxazole increased from 0.24 × 100,000 to 0.30 × 100,000 defined daily doses.. The incidence of PCP is rising rapidly and represents a significant burden to the healthcare system. Further study into who is at risk of PCP is needed to better determine who should be given prophylaxis.

Topics: England; Humans; Incidence; Opportunistic Infections; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Risk Assessment; Trimethoprim, Sulfamethoxazole Drug Combination

To identify a specific population of patients with rheumatic diseases receiving rituximab treatment for whom the benefit from primary prophylaxis against Pneumocystis jirovecii pneumonia (PJP) outweighs the risk of adverse events (AEs).. This study included 818 patients treated with rituximab for rheumatic diseases, among whom 419 received prophylactic trimethoprim/sulfamethoxazole (TMP/SMX) with rituximab, while the remainder did not. Differences in 1-year PJP incidence between the groups were estimated using Cox proportional hazards regression. Risk-benefit assessment was performed in subgroups stratified according to risk factors based on the number needed to treat (NNT) to prevent 1 case of PJP and the number needed to harm (NNH) due to severe AEs. Inverse probability of treatment weighting was applied to minimize the confounding by indication.. During the 663.1 person-years, there were 11 PJP cases, with a mortality rate of 63.6%. Concomitant use of high-dose glucocorticoids (≥30 mg/day of prednisone or equivalent during 4 weeks after rituximab administration) was the most important risk factor. The PJP incidence (per 100 person-years) was 7.93 (95% confidence interval [95% CI] 2.91-17.25) in the subgroup receiving high-dose glucocorticoids compared with 0.40 (95% CI 0.01-2.25) in the subgroup without high-dose glucocorticoid use. Although prophylactic TMP/SMX significantly reduced the overall PJP incidence (HR 0.11 [95% CI 0.03-0.43]), the NNT to prevent 1 case of PJP (146) was higher than the NNH (86). In contrast, the NNT fell to 20 (95% CI 10.7-65.7) in patients receiving concomitant high-dose glucocorticoids.. The benefit associated with primary PJP prophylaxis outweighs the risk of severe AEs in patients with rheumatic diseases receiving rituximab and concomitant high-dose glucocorticoid treatment.

Topics: Glucocorticoids; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Rheumatic Diseases; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial of first choice in the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients, particularly in people living with human immunodeficiency virus (HIV). TMP/SMX use entails different adverse effects, and its association with early neutropenia is minimally documented. This study aimed to identify the risk of early neutropenia associated with TMP/SMX use in adults living with HIV in Mexico.. A prospective cohort study was conducted in TMP/SMX-naïve adults living with HIV admitted to a third-level hospital between August 2019 and March 2020. Socio-demographic, clinical, and laboratory data were collected. According to patients' diagnostic, if they required treatment or prophylaxis against PCP, medical staff decided to prescribe TMP/SMX, as it is the first-line treatment. The risk of TMP/SMX induced early neutropenia, as well as associated factors were analyzed through a bivariate model and a multivariate Poisson regression model. The strength of association was measured by incidence rate ratio (IRR) with 95% confidence interval.. 57 patients were enrolled in the study, of whom 40 patients were in the TMP/SMX treatment-group for treatment or prophylaxis of PCP (204.8 person-years of observation, median 26.5 days) and 17 patients were in the non-treatment group because they did not need the drug for treatment or prophylaxis of PCP (87.0 person-years of observation, median 21 days). The incidence rate of early neutropenia in the TMP/SMX-treatment group versus non-treatment group was 7.81 and 1.15 cases per 100 person-years, respectively. After adjusting for stage 3 of HIV infection and neutrophil count <1,500 cells/mm3 at hospital admission, the current use of TMP/SMX was not associated with an increase in the incidence rate ratio of early neutropenia (adjusted IRR: 3.46; 95% CI: 0.25-47.55; p = 0.352).. The current use of TMP/SMX in Mexican adults living with HIV was not associated with an increase in the incidence rate ratio of early neutropenia.

Topics: Adult; Cohort Studies; HIV; HIV Infections; Humans; Mexico; Neutropenia; Pneumonia, Pneumocystis; Prospective Studies; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Clinical Trials as Topic; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

B-cell lymphoma is the most prevalent type of non-Hodgkin lymphoma, for which the standard treatment regimen includes rituximab combined with CHOP. However, some patients may develop interstitial pneumonitis (IP), which can be caused by various factors; one of the most important factors is Pneumocystis jirovecii. It is crucial to investigate the pathophysiology of IP and implement preventive measures since IP can be fatal for some people. The data were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, where patients with B-cell lymphoma received the R-CHOP/R-CDOP regimen with or without prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX). Multivariable logistic regression and propensity score matching (PSM) were used to investigate any potential association. Eight hundred thirty-one patients with B-cell lymphoma were classified into two groups: the non-prophylaxis group without TMP-SMX (n=699) and the prophylaxis group with TMP-SMX (n = 132). IP occurred in 66 patients (9.4%, all in the non-prophylaxis group), with an onset median of three cycles of chemotherapy. Multiple logistic regression analysis demonstrated that IP incidence was associated with pegylated liposome doxorubicin (OR=3.29, 95% CI 1.84-5.90, P<0.001). After utilizing a 1:1 matching algorithm for PSM, 90 patients from each group were obtained. There was a statistical difference between the two cohorts in the IP incidence (non-prophylaxis 12.2% vs prophylaxis 0.0%, P <0.001). The prophylactic use of TMP-SMX could prevent the occurrence of IP whose risk factor was pegylated liposome doxorubicin after chemotherapy for B-cell lymphoma.

Topics: Cyclophosphamide; Doxorubicin; Humans; Liposomes; Lung Diseases, Interstitial; Lymphoma, B-Cell; Pneumonia, Pneumocystis; Polyethylene Glycols; Prednisone; Propensity Score; Retrospective Studies; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

The number of pneumocystis pneumonia (PCP) cases is increasing in immunocompromised patients without human immunodeficiency virus infection (HIV), causing serious morbidity with high mortality. Trimethoprim/sulfamethoxazole (TMP/SMZ) monotherapy has limited effectiveness in the treatment of PCP. Clinical data on whether initial caspofungin plus TMP/SMZ for this disease is superior to monotherapy in non-HIV-infected patients are limited. We aimed to compare the clinical effectiveness of these regimens for severe PCP in non-HIV patients.. A retrospective study reviewed 104 non-HIV-infected patients with confirmed PCP in the intensive care unit between January 2016 and December 2021. Eleven patients were excluded from the study because TMP/SMZ could not be used due to severe hematologic disorders or clinical data were missing. All enrolled patients were divided into three groups according to different treatment strategies: Group 1 received TMP/SMZ monotherapy, Group 2 received caspofungin combined with TMP/SMZ as first-line therapy, and Group 3 initially received TMP/SMZ monotherapy and later received caspofungin as salvage therapy. The clinical characteristics and outcomes were compared among the groups.. A total of 93 patients met the criteria. The overall positive response rate of anti-PCP treatment was 58.06%, and the overall 90-day all-cause mortality rate was 49.46%. The median APACHE II score was 21.44. The concurrent infection rate was 74.19%, among whom 15.05% (n = 14) of those patients had pulmonary aspergillosis, 21.05% (n = 20) had bacteremia, and 23.65% (n = 22) had CMV infections. The patients who received initial caspofungin combination with TMP/SMZ had the best positive response rate (76.74%) compared to others (p = 0.001). Furthermore, the group that received initial caspofungin combined with TMP/SMZ had a 90-day all-cause mortality rate (39.53%) that was significantly different from that of the shift group (65.51%, p = 0.024), but this rate showed no statistically significant difference compared with that in the monotherapy group (48.62%, p = 0.322). None of the patients had serious adverse events from caspofungin therapy.. For non-HIV-infected patients with severe PCP, initial combination therapy with caspofungin and TMP/SMZ is a promising first-line treatment option compared with TMP/SMZ monotherapy and combination therapy as salvage therapy.

Topics: Adult; Aged; Caspofungin; Drug Combinations; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

This JAMA Insights Clinical Update discusses current recommendations regarding prevention of Pneumocystis pneumonia in patients who are immunocompromised.

Topics: Adult; Chemoprevention; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Restrictive lung disease leading to abnormal lung function in kidney transplant recipients is commonly associated with noninfectious complications or medications used for post-transplant immunosuppression. Herein, we report an interesting case of pediatric kidney transplant recipient with weight loss and abnormal spirometry who was diagnosed to have late-onset Pneumocystis pneumonia.. A 17-year-old male patient with a history of allergic rhinitis, mild persistent asthma, and deceased donor kidney transplant, performed 18 months prior, presented for routine evaluation of his asthma to the pulmonology clinic. He was clinically asymptomatic except for a weight loss of 8 kg over 6-month period prior to presentation. Patient's spirometry was suggestive of a restrictive pattern and further investigation using a high-resolution computed tomography (HRCT) of the chest showed bilateral diffuse ground-glass reticulonodular opacities with subpleural sparing suggestive of interstitial pneumonitis. A bronchoscopy with bronchoalveolar lavage revealed organisms consistent with Pneumocystis jirovecii on gomori-methenamine-silver (GMS) staining. Beta-d-glucan testing in serum revealed a level of >500 pg/mL (normal 0-59 pg/mL) further supportive of Pneumocystis jirovecii infection. Patient was treated with a 6-week course of trimethoprim-sulfamethoxazole. His weight loss and beta-d-glucan levels improved over a course of 6 months, and he continues to be on trimethoprim-sulfamethoxazole prophylaxis.. Late-onset Pneumocystis jirovecii infection in kidney transplant recipients can have an atypical presentation. Treating physicians should consider PJP in the differential diagnosis of unexplained weight loss in pediatric kidney transplant recipients, especially those receiving a large cumulative burden of immunosuppression.

Topics: Adolescent; Child; Humans; Immunosuppression Therapy; Kidney Transplantation; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate drug concentration of trimethoprim-sulfamethoxazole (TMP-SMX) using therapeutic drug monitoring (TDM) for severe. A 72-year-old man with hypoxemic respiratory failure due to COVID-19 infection was admitted to the intensive care unit for invasive mechanical ventilation. The patient developed acute renal failure that required RCA-CVVH. Pulmonary co-infection with PJP was diagnosed, and a high TMP-SMX dose was initiated according to (inter)national guidelines with dose reduction after 3 days because of renal failure. Population pharmacokinetics were assessed for TMP and SMX as well as clearance by RCA-CVVH, volume of distribution, and time above threshold levels for measured plasma concentrations.. During renal failure requiring RCA-CVVH, a corresponding dose reduction of TMP-SMX to 320/1,600 mg twice a day, according to current Dutch SWAB and Dutch Association of Hospital Pharmacists guidelines, resulted in unintended under-dosing with sub-therapeutic TMP-SMX concentrations. Pharmacokinetic modeling and dose adjustment of TMP-SMX to 640/3,200 mg 3 times daily resulted in steady-state TMP-SMX peak concentrations associated with efficacy against PJP. Hence, the patient was successfully weaned from the ventilator and discharged.. We hypothesize that our new dose recommendation of 640/3,200 mg TMP-SMX 3 times daily is associated with an increased probability of critical patients being successfully liberated from mechanical weaning following PJP pneumonia and COVID-19 infection.

Topics: Aged; Coinfection; Continuous Renal Replacement Therapy; COVID-19; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Renal Insufficiency; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

We investigated the expression of PJP in patients with hematological disease who received atovaquone administration. Atovaquone was administered at a low dose of 750 mg once daily, and the follow-up time was the period of PJP prophylaxis that included atovaquone administration.. 85 patients were included in the study. The median age of the study population was 72 years (range: 33 - 97). The duration of atovaquone treatment and follow-up time were 150 days (22 - 1,018) and 258 days (22 - 1,457), respectively. In hematologic diseases, multiple myeloma was high in 31 patients and malignant lymphoma in 28 patients. No patients exhibited PJP during the observation period.. In hematological disease patients with relatively low risk of PJP, low-dose atovaquone may prevent the onset of PJP.

Topics: Adult; Aged; Aged, 80 and over; Atovaquone; Hematologic Diseases; Humans; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in organ transplant recipients that may be prevented by antibiotic prophylaxis. We aimed to investigate the incidence rate (IR) of PCP and the related hospitalization and mortality rates in liver transplant recipients in an era of routine prophylaxis.. We included all adult liver transplant recipients transplanted at Rigshospitalet between January 1, 2011 and October 1, 2019. Microbiology data were obtained from the Danish Microbiology Database (MiBa), a national database containing all data from all Departments of Clinical Microbiology in Denmark receiving samples from both hospitals and general practices. According to local guidelines, PCP prophylaxis was initiated 1 week posttransplantation and discontinued after 6 months or sooner in patients experiencing side effects.. We included 343 liver transplant recipients with 1153 person-years of follow-up (PYFU), of which 269 (78%) received PCP prophylaxis during the first 6 months posttransplantation. Seven (2%) recipients were diagnosed with PCP during follow-up. In the first 6 months posttransplantation and in 269 transplant recipients who received prophylaxis there were zero PCP events while the IR was 32 (95% confidence interval [CI] 2.9-148) per 1000 PYFU in 74 recipient who did not receive prophylaxis. During 7th to 12th month posttransplantation the IR was 20 (95% CI: 5.5-53) per 1000 PYFU. All seven (100%) recipients diagnosed with PCP were hospitalized, however none died.. PCP was not detected in liver transplant recipients while on prophylaxis. Though, it worth mentioning that two out of the seven PCP patients received high-dose prednisolone before the PCP event. All liver transplant recipients with PCP were hospitalized, but none died. Randomized clinical trials to determine the optimal duration of prophylaxis are warranted.

Topics: Adult; Antibiotic Prophylaxis; Humans; Liver Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Although previous studies suggested that rituximab increases the risk of Pneumocystis jirovecii pneumonia (PJP), it is uncertain whether its primary prophylaxis for PJP is justified.. Does the benefit of primary prophylaxis for PJP in patients receiving rituximab treatment outweigh the potential risk of the prophylaxis?. This retrospective study included 3,524 patients (hematologic diseases, 2,500; rheumatic diseases, 559; pre/post-solid organ transplantation, 465) first exposed to rituximab between 2002 and 2018 in a tertiary referral center in South Korea. Patients were classified into a control group (n = 2,523) and a prophylaxis group (n = 1,001) according to the administration of prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) during the first 28 days after the start of rituximab (intention-to-treat analysis). In addition, exposure to TMP-SMX was examined as a time-varying variable (time-varying analysis). The primary outcome was the prophylactic effect of TMP-SMX on the 1-year incidence of PJP. Inverse probability of treatment weights was applied to minimize the baseline imbalance. The secondary outcome included the incidence of adverse drug reactions (ADRs) related to TMP-SMX.. Over 2,759.9 person-years, 92 PJP infections occurred, with a mortality rate of 27.2%. The prophylaxis group showed a significantly lower incidence of PJP (adjusted subdistribution hazard ratio, 0.20 [95% CI, 0.10-0.42]) than the control group. This result was consistent with the results of time-varying analysis, in which only one PJP infection occurred during TMP-SMX administration (adjusted subdistribution hazard ratio, 0.01 [0.003-0.16]). The incidence of ADRs related to TMP-SMX was 18.1 (14.6-22.2)/100 person-years, and most were of mild to moderate severity. On the basis of 10 severe ADRs, the number needed to harm was 101 (61.9-261.1), whereas the number needed to prevent one PJP infection was 32 (24.8-39.4).. TMP-SMX prophylaxis significantly reduces PJP incidence with a tolerable safety profile in patients receiving rituximab treatment.

Topics: Humans; Pneumonia, Pneumocystis; Retrospective Studies; Rheumatic Diseases; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination

A 67-year-old male with chronic lymphocytic leukemia was admitted with headaches and ring-enhancing lesions on magnetic resonance imaging of the brain. His current regimen included rituximab and ibrutinib with trimethoprim-sulfamethoxazole for secondary Pneumocystis jirovecii pneumonia prevention. All other elements of his history were noncontributory. The diagnosis of an invasive fungal infection was made via light microscopy of a stereotactic brain biopsy specimen.

Topics: Abscess; Aged; Brain; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Rituximab is widely used as the first-line treatment for pemphigus patients. Since it depletes the B cells, it increases the risk of infections. Here, we evaluated the prophylactic efficacy of cotrimoxazole in decreasing the risk of pneumocystis pneumonia (PCP) infection in the pemphigus patients treated with rituximab. The medical records of confirmed pemphigus patients receiving rituximab were evaluated in two groups; those who received cotrimoxazole as a prophylactic after rituximab and patients who only received rituximab without any prophylaxis. The occurrence of PCP infection was determined in each group and compared. Medical records of 494 patients, including 301 women and 193 men, with the mean age of 46.74 years were analyzed. The phenotypes of the disease were mucocutaneous (n = 364), mucosal (n = 88), and cutaneous (n = 42). Among them, 235 cases had received cotrimoxazole as a prophylaxis and 259 patients did not. The incidence of PCP in total patients was 2 (0.4%), one in each group. Accordingly, no significant difference was observed in the incidence of PCP between two groups (p = 0.84). Also, no cotrimoxazole-related side effect was observed in the treated group. It seems that due to the low incidence of PCP in pemphigus patients treated with rituximab, prophylactic cotrimoxazole therapy is not necessary and it only increases the overall therapy cost and might cause cotrimoxazole-related adverse effects in some patients. However, regarding its probable beneficial effect in patients with long-term history of immunosuppressive therapy, more studies are required.

Topics: Female; Humans; Pemphigus; Pneumonia, Pneumocystis; Retrospective Studies; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PJP) occurs in immunocompromised hosts. It is classified as PJP with human immunodeficiency virus (HIV) infection (HIV-PJP) and PJP without HIV infection (non-HIV PJP). Compared with HIV-PJP, non-HIV PJP is more likely to develop rapidly into respiratory failure, with difficult diagnosis and high mortality.. A 46-year-old male with membranous nephropathy was treated with oral corticosteroids and tacrolimus. He was admitted to our hospital for fever and dyspnea which developed 4 days ago. Laboratory data revealed that leukocytes were 10.99 × 109/L, neutrophils 87.7%, lymphocytes 9.6%, C-reactive protein 252.92 mg/L, New coronavirus nucleic acid detection negative. CT scan of chest revealed ground-glass opacity in both lungs. He was admitted to the respiratory department of our hospital, and then transferred to ICU because of his critical condition.. High throughput gene detection of pathogenic microorganisms in alveolar lavage fluid showed that the detection sequence of Pneumocystis yersiniae increased significantly. The serum HIV-antibody was negative. Therefore, the patient was diagnosed as non-HIV PJP.. After admission, the patient was assisted by noninvasive ventilator and treated with compound trimethoprim-sulfamethoxazole (SMX-TMP) and caspofungin. The patient's condition continued to deteriorate, and then underwent endotracheal intubation and veno-venous extracorporeal membrane oxygenation (VV-ECMO) combined with prone position ventilation until the lung lesion improved.. VV-ECMO was stopped on day 12, tracheal intubation was removed after 2 days. The patient was transferred to the respiratory department on day 15, discharged after 12 days without complications. Two months later, the follow-up showed that the patient was in good condition.. VV-ECMO combined with prone position ventilation could be a useful choice for respiratory assistance in non-HIV PJP patients.

Topics: Caspofungin; Extracorporeal Membrane Oxygenation; Humans; Lung; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prone Position; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

In the era of effective prophylaxis, the objective of this study was to describe pneumocystis pneumonia (PCP) patients' profile and evaluate the consistency of clinical situations encountered with the recommended indications for prophylaxis.. This was a single-centre, retrospective study. All adults (> 18 years) with a definitive diagnosis of PCP were included. Data were collected from patients' electronic medical files.. The study examined the medical files of 225 patients diagnosed with PCP and treated between 1 January, 2015, and 30 June, 2020. More than 95% of the patients were not on anti-PCP prophylaxis at the time of PCP diagnosis. There were 32 (14%) deaths before the end of PCP treatment, mainly in auto-immune disease (30%) and solid tumours (38%) groups unlike the solid-organ transplants group, among whom deaths were infrequent. Indeed, 48% of our cohort (n = 107) had both corticosteroid (CS) therapy, immunosuppressive or immunomodulatory treatment, and lymphopaenia and could have been considered at high risk for PCP. Trimethoprim/sulfamethoxazole was administered as first-line PCP curative treatment in 95% of the patients. Toxicities of this drug led to treatment interruption in 25% of the patients (except death).. This study found a high number of PCP cases over 5 years. Unsurprisingly, most of the patients were immunosuppressed, with risk factors for PCP already described in the literature. This large number of PCP cases should be avoidable and, consequently, questions arise. Faced with these data, prophylaxis should be common sense for immunocompromised patients with risk factors, even if formalised recommendations do not exist.

Topics: Adult; Humans; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Malignant gliomas are treated with temozolomide chemoradiotherapy. Because pneumocystis pneumonia (PCP) can occur in patients receiving temozolomide, the product monograph recommends PCP prophylaxis during temozolomide chemoradiotherapy. Not all neuro-oncologists follow these recommendations, though.. We performed a population-based retrospective cohort study of glioma patients undergoing temozolomide chemoradiotherapy 2005 to 2019 in Ontario, Canada. A propensity score model was used to predict the use of PCP prophylaxis. We compared the risk of PCP within 90 days of starting radiotherapy with versus without PCP prophylaxis using inverse probability of treatment weighting (IPTW). We also examined overall survival, hospitalizations, and myelosuppression.. There were 3,225 patients included in the cohort (648 received antibiotics and 2,434 did not). Only 18 patients developed PCP within 90 days of therapy. The IPTW-adjusted absolute risk reduction in PCP with antibiotics was 0.0035 (95% CI, -0.0013 to 0.0083), number needed to treat: 288. Neither overall survival nor hospitalization count differed between the groups. The number needed to harm by causing grade 3/4 neutropenia was 39.. In regions (like Ontario) where PCP is rare, routine PCP prophylaxis with trimethoprim-sulfamethoxazole should not be offered, since the harms may outweigh the benefits.

Topics: Anti-Bacterial Agents; Chemoradiotherapy; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Temozolomide; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the clinical features, early diagnosis, and treatment methods of Pneumocystis jirovecii pneumonia (PJP) after renal transplantation (RT).. We retrospectively analyzed the clinical data of 80 patients with confirmed PJP who underwent RT between 2018 and 2021 in our hospital.. In the present study, the incidence of PJP was 6.2% (80/1300). A 50% of cases (40 out of 80 patients) had developed a PJP infection during the first 6 months after RT and 81.3% (65 out of 80 patients) within 12 months. The median onset time of PJP was 6.5 months after RT. The most common symptom was fever (73.8%), followed by progressive dyspnea (51.3%) and dry cough (31.3%). In the initial phase of PJP, the most frequent CT finding was the presence of diffuse ground-grass shadows. In all, 27.5%, 37.5%, and 35% patients were diagnosed by induced sputum metagenomic next-generation sequencing (mNGS), peripheral blood mNGS, and characteristic clinical diagnostic features, respectively. The median 1,3-β-D-glucan level was 500 pg/mL, while the median C-reactive protein level was 63.4 mg/L. In most patients (83.8%), the procalcitonin levels were negative. The mean serum creatinine level was 171.9 ± 87.4 μmol/L. Of the 80 patients, 37 (46.2%) had coexisting cytomegalovirus (CMV) infection. All patients were treated with trimethoprim-sulfamethoxazole and third generation cephalosporin to prevent bacterial infection. The methylprednisolone dose (40-120 mg/d) varied according to illness.. PJP usually occurs within 1 year after RT, typically within 6 months. Fever, dry cough, and progressive dyspnea are the most common clinical symptoms. PJP should be highly suspected if the patient has clinical symptoms and diffuse, patchy, ground-glass opacities on CT in both lungs after RT within 1 year. Peripheral blood or induced sputum mNGS is helpful for early diagnosis of PJP. Trimethoprim-sulfamethoxazole is still the first choice for the treatment of PJP. Combined use of caspofungin can reduce the dose and adverse reactions of trimethoprim-sulfamethoxazole in theory.

Topics: Cough; Cytomegalovirus Infections; Dyspnea; Humans; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is a common opportunistic fungal pathogen that commonly affects immunocompromised individuals and can cause P. jirovecii pneumonia. Extrapulmonary P. jirovecii infections are extremely rare. Herein, we present a case of an HIV-positive, antiretroviral therapy-naïve patient who had extrapulmonary pneumocystosis (EPC). He presented with complaints of decreased appetite, abdominal fullness, and weight loss. Computed tomography (CT) revealed multiple low-attenuation masses in the spleen, liver, and both adrenal glands but no pulmonary involvement. A core-needle biopsy of a splenic lesion confirmed the diagnosis of EPC. The patient was initiated on intravenous trimethoprim-sulfamethoxazole (TMP-SMX) and CT-guided percutaneous catheter drainage of the splenic lesion was performed. Intravenous TMP-SMX therapy was completed in 3 weeks and intravenous pentamidine (250 mg daily) therapy was commenced. Pentamidine was completed after 3 weeks, and antiretroviral treatment (ART) was initiated with dolutegravir 50 mg and Descovy HT (emtricitabine [200 mg] and tenofovir alafenamide fumarate [25 mg]). After starting ART, the patient's clinical condition improved, and the abscesses gradually reduced. TMP-SMX is commonly used to treat EPC; however, there is no standard method of treatment. ART may become the key to EPC treatment in individuals with HIV infection.

Topics: HIV Infections; HIV Seropositivity; Humans; Male; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection. In non-HIV immunocompromised patients with PCP, a standard second-line treatment has not been established up to now.. Non-HIV immunocompromised patients with confirmed PCP between April 2013 and December 2020 were included. Their PCP treatment history was tracked. Factors related to first-line trimethoprim/sulfamethoxazole (TMP/SMX) and second-line treatment failure were identified. Different second-line treatment strategies were compared.. Among the 220 patients, 127 (57.73%) did not respond to first-line TMP/SMX treatment. Risk factors related to treatment failure included symptom triad with breathlessness at rest, persistent fever and cough (85% in the treatment failure group versus 74% in the treatment success group, P = 0.034), treatment with invasive mechanical ventilation (67 vs. 19%, P < 0.001), coinfection with CMV (69 vs. 47%, P = 0.035), and bacteremia (59 vs. 10%, P < 0.001). A total of 49 patients received second-line treatment on the basis of TMP/SMX, and 28 (57.1%) of them responded to the treatment. No clinical parameter, including selection of different therapies, was found to be significantly associated with second-line treatment failure. Further, the prognosis of different second-line therapies showed no drug or drug combination strategy superior to others. The primaquine group had lower 90-day mortality rate (45.9%) but showed no statistically significant difference compared with the non-primaquine group (64.6%). The patients in the clindamycin plus primaquine group had the lowest in-hospital mortality rate (22.2%, P = 0.042) among different second-line therapies, although the in-hospital mortality of the primaquine group was not significantly different from that of the non-primaquine group. The differences in 28 day mortality and overall mortality rates were not statistically significant, too.. CMV infection and bacteremia were risk factors significantly associated with treatment failure of TMP/SMX. The response and survival rates of second-line treatment, including clindamycin, primaquine, and caspofungin, were poor, maybe clindamycin plus primaquine as second line treatment was better than other treatment strategies. These results suggest that clinicians should carefully evaluate whether the treatment of TMP/SMX has failed due to a coinfection rather than hastily changing to a second-line drug when the patient worsens.

Topics: Bacteremia; Clindamycin; Coinfection; Cytomegalovirus Infections; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Primaquine; Prognosis; Retrospective Studies; Treatment Failure; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Glucocorticoids; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Prostatic Neoplasms; Trimethoprim, Sulfamethoxazole Drug Combination

BACKGROUND Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that commonly occurs in immunocompromised patients, especially those with HIV. Early diagnosis and prompt treatment are important because PJP is a potentially life-threatening infection. However, the diagnosis of PJP in the early stage can be challenging due to various factors. Furthermore, the early presentation of PJP, which includes normal chest radiograph and examination findings along with the subacute presentation of PJP in patients with HIV, makes an early diagnosis of the disease even more challenging for doctors. CASE REPORT In this case report, we present the case of a 39-year-old man who had normal chest X-ray findings during the initial stage of his presentation. Coupled with non-disclosure of HIV status, these led to a delay in PJP diagnosis. The diagnosis of PJP with underlying HIV was later supported by the patient's clinical features, initial blood investigations, and presence of high-risk sexual activity. The diagnosis was confirmed when the PJP polymerase chain reaction test from the respiratory sample was positive. He was successfully treated with oral trimethoprim-sulfamethoxazole. However, he subsequently developed rare adverse effects of drug-induced immune hemolytic anemia, which was diagnosed based on the presence of hemolytic anemia and recent exposure to a new drug. Trimethoprim-sulfamethoxazole was promptly discontinued, which resulted in symptom improvement. CONCLUSIONS This case report aims to create awareness among primary care doctors to be vigilant of the PJP diagnosis and its nonspecific presentations as well as to the rare adverse effects of medications to treat PJP.

Topics: Adult; Anemia, Hemolytic; HIV Infections; Humans; Immunocompromised Host; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PJP) is infrequently found in patients with acute myeloid leukemia (AML) whereas its more commonly found in lymphoid malignancies like acute lymphoblastic leukemia and various lymphomas. AML patients are conventionally treated with intensive chemotherapeutic regimen which includes Daunorubicin, Idarubicin, Cytarabine and various other drugs. Trimethoprim/Sulfamethoxazole prophylaxis is not routinely administered to such patients. In recent years, targeted therapies like Venetoclax which is a Bcl-2 inhibitor have been introduced for AML treatment which is given in combination with other chemotherapy and targeted molecules. There is tremendous use of Venetoclax for AML recently specially in unfit and elderly population. We are witnessing this uncommon infection more commonly in those patients treated with Venetoclax based therapy. We report the case series of five patients of AML who were treated with Venetoclax based therapy and had subsequently developed PJP leading to death in four of them. The incidence of PJP was 13.2% among the patients treated with Venetoclax based treatment at our institution in that timeframe. The low index of suspicion led to delay in diagnosis and thereby treatment. Such an association of Venetoclax and Pneumocystis jirovecii pneumonia has not been reported till date, so this prompts for early detection and treatment of this potentially life threatening but treatable infection. So the role of routine prophylaxis with Trimethoprim/Sulfamethoxazole in those receiving Venetoclax based therapy in AML patients merits a thought.

Topics: Aged; Bridged Bicyclo Compounds, Heterocyclic; Cytarabine; Humans; Idarubicin; Leukemia, Myeloid, Acute; Pneumocystis carinii; Pneumonia, Pneumocystis; Proto-Oncogene Proteins c-bcl-2; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

The purpose of this single-center retrospective case series was to evaluate the efficacy and safety of 300-mg once-monthly intravenous (IV) pentamidine prophylaxis in 702 adult allogeneic hematopoietic stem cell transplant (HSCT) patients. We observed no cases of Pneumocystis jirovecii pneumonia (PJP) following IV pentamidine administration. Breakthrough

Topics: Adult; Hematopoietic Stem Cell Transplantation; Humans; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the efficacy and safety of low-dose trimethoprim (TMP)-sulfamethoxazole (SMX) (TMP-SMX) as the primary prophylaxis for Pneumocystis jirovecii pneumonia (PJP) in adult recipients of kidney transplantation.. Three kinds of prescriptions in kidney recipients were documented, including 20 mg TMP/100 mg SMX oral daily, 20 mg TMP/100 mg SMX oral every other day, and nonprophylaxis. The primary outcome was the incidence of PJP in the first 180 days of follow-up after kidney transplantation. The secondary outcomes were changes in renal and liver function.. Among the 1469 recipients, 1066 (72.56%) received 20 mg TMP/100 mg SMX daily, 127 (8.65%) received 20 mg TMP/100 mg SMX every other day, and 276 (18.79%) did not have prophylaxis prescription. The 276 recipients in the nonprophylaxis group had 124.92 person-years of follow-up, during which PJP occurred in 29 patients, for an incidence rate of 23.21 (95% confidence interval 15.76-32.72) per 100 person-years. The TMP-SMX daily group and the TMP-SMX every other day group had 524.89 and 62.07 person-years of follow-up, respectively, with no occurrence of PJP. There was no significant difference among the three groups in changes in renal and liver function (P >0.05, respectively). A total of 111 recipients in each group were enrolled in the propensity score matching analysis. It was revealed that the 111 nonprophylaxis recipients had 51.27 person-years of follow-up and 10 PJP cases. Prophylaxis was considered effective because there was a significant difference between the three groups (P <0.001).. Low-dose TMP-SMX prophylaxis significantly reduces the incidence of PJP within 6 months after kidney transplantation and has a favorable safety profile.

Topics: Adult; Humans; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening disease with increasing prevalence in patients with rheumatic disease. Trimethoprim/sulfamethoxazole (TMP/SMX) is an effective treatment for patients with rheumatic disease hospitalized for PJP. This study aimed to describe the 90-day mortality of patients with rheumatic disease complicated by PJP and investigate whether the administration of TMP/SMX after 7 days from initial symptoms correlates with 90-day mortality.. We enrolled consecutive patients with rheumatic disease complicated with PJP in our center from August 2018 to August 2021. The participants were classified into two groups according to when TMP/SMX was initiated: early (within the first 7 days) and late (after 7 days). The primary outcome was 90-day PJP-related mortality. Multivariate cox regression and Kaplan-Meier survival analyses were conducted to identify the risk factors for mortality and examine differences in survival between early and late use of TMP/SMX.. Thirty-seven patients with rheumatic disease (median age 50.1 years, 24.3% male) complicated by PJP were enrolled in our study, and 15 (40.5%) patients died at or before 90 days of follow-up. The most common comorbidity was systemic lupus erythematosus (14, 37.8%), followed by inflammatory myopathy (11, 27.9%). Patients in the early group were less likely to require mechanical ventilation (8/27, 29.6% vs. 9/10, 90.0%, P = 0.002), lower doses glucocorticoids (43.2 mg/d vs. 72.2 mg/d, P = 0.039) and had lower mortality (7/27, 25.9% vs. 8/10, 80.0%, P = 0.006) than those in the late group. In the Kaplan-Meier analysis, the survivor probability of the early group was notably higher than that of the late group (P = 0.007). Multivariate cox regression analysis showed that initiation of TMP/SMX after 7 days from admission (hazard ratio [HR]: 5.9, 95% confidence interval [CI]: 1.1-30.4; P = 0.034) and a higher level of lactate dehydrogenase (LDH; HR: 6.0, 95% CI: 1.1-31.8; P = 0.035) were associated with 90-day mortality in patients with rheumatic disease complicated by PJP.. Patients with rheumatic disease complicated by PJP had poor prognoses, with mortality rates as high as 40.5%. TMP/SMX initiation after 7 days from initial symptoms and a higher level of serum LDH were significantly associated with increased 90-day mortality.

Topics: Female; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Rheumatic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

A 49-year-old woman had been treated with adjuvant dose-dense chemotherapy for left breast cancer pT2N2aM0, Stage ⅢA. She developed a fever of over 38°C on day 13 of the third course of dose-dense doxorubicin/cyclophosphamide (AC)chemotherapy. She was started on oral levofloxacin, but the fever did not resolve. COVID-19 PCR test was positive and chest CT scan showed bilateral ground-glass opacities. She was diagnosed with COVID-19 pneumonia and hospitalized. The fever did not resolve even after sotrovimab and remdesivir were administered. On the 5th hospital day, the serum β-D-glucan level was found to be elevated(81.7 pg/mL), and she was diagnosed with concurrent COVID-19 and Pneumocystis jirovecii pneumonia(PCP). After the start of sulfamethoxazole-trimethoprim(TMP-SMX), the fever resolved quickly. After discharge from hospital, ground-glass opacities had disappeared. She resumed dose-dense chemotherapy with TMP-SMX and completed without fever. In immunosuppressed patients with cancer drug therapy, it is necessary to make a differential diagnosis of various types of pneumonia and to consider the different types of pneumonia may occur simultaneously.

Topics: Breast Neoplasms; COVID-19; Female; Humans; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

We compared the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) with atovaquone for pneumocystis pneumonia (PCP) in patients with connective tissue diseases (CTDs) receiving high-dose glucocorticoids. Patients with CTDs aged ≥ 18 years who were treated with a prolonged course (≥ 4 weeks) of glucocorticoids (≥ 20 mg/day prednisone) in a Japanese tertiary center between 2013 and 2017 were included. The patients were categorized into two groups: TMP-SMX and atovaquone group. Adjusted cumulative incidence of PCP was compared between the two groups after propensity score weighting for differences in confounding factors. A total of 480 patients with a prolonged high-dose glucocorticoid treatment were identified. Out of 383 patients with TMP-SMX prophylaxis, 102 (26.8%) patients experienced adverse events leading to discontinuation within 4 weeks of initiation, while no patient in the atovaquone discontinued the therapy. Two hundred eighty-one patients received TMP-SMX, while 107 received atovaquone for PCP prophylaxis. During a total of 397.0 person-years, 7 PCP cases (2 in the TMP-SMX, 5 in the atovaquone) occurred with a mortality rate of 54.5%. After adjusting for differences in baseline characteristics, the adjusted cumulative incidence of PCP was similar between the two group (HR 0.97, 95% CI 0.19-5.09, p = 0.97). Prophylactic effects for PCP in CTDs patients receiving prolonged high-dose glucocorticoids were similar between TMP-SMX and atovaquone. Atovaquone was well-tolerated with no side effects.

Topics: Atovaquone; Connective Tissue Diseases; Glucocorticoids; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The use of biologic and targeted synthetic (b/ts) DMARDs in the treatment of RA is increasing. Therefore, prevention of b/tsDMARDs-induced infection is important. Here we describe a prophylaxis protocol for preventing pneumocystis pneumonia (PCP) in RA patients treated with b/tsDMARDs.. The study subjects were 3787 RA patients from the FIRST registry. They were divided into cohort 1 (n = 807, requiring prophylaxis against PCP based on physicians' assessment at the point of new treatment with or switch to b/tsDMARDs) and cohort 2 (n = 2980, receiving strategic PCP prophylaxis). The incidence and risk factors for PCP were investigated.. Twenty-six PCP cases were observed throughout the study. After the introduction of strategic PCP prophylaxis, PCP incidence diminished from 0.51/100 person-years (PYs) to 0.21/100 PYs (risk ratio = 0.42). Sulfamethoxazole and trimethoprim in combination (SMX-TMP) showed greater efficacy in the prevention of PCP than pentamidine inhalation (P <0.0001). The prophylaxis rate increased chronologically despite the falls in the average SMX-TMP dose and in the incidence of PCP. Subanalysis of the data for 929 patients from both groups who did not receive prophylaxis showed that old age, high BMI, coexisting lung diseases, low lymphocyte count, and low serum IgG levels increased the risk of PCP development. Development of PCP could be predicted (using an equation based on these variables) in patients not treated with glucocorticoids [area under the curve (AUC) = 0.910)], but less accurately in those on glucocorticoids (AUC = 0.746).. Our study clarified the risk factors for PCP in RA patients on b/tsDMARDs treatment and highlighted and defined the criteria for effective prophylaxis against PCP.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Glucocorticoids; Humans; Pneumonia, Pneumocystis; Registries; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Tropheryma

Objectives To determine the performance of droplet digital polymerase chain reaction (ddPCR) assays in diagnosing Pneumocystis pneumonia (PCP), and to survey the sulfamethoxazole-trimethoprim (SMX-TMP) resistant mutations in our PCP cohort. Methods A prospective study was conducted from January 2017 to June 2018. Adult immunocompromised subjects with pneumonia were enrolled. Bronchoalveolar lavage fluid samples were obtained for standard microscopic testing and ddPCR to quantify the Pneumocystis MSG gene. DHPS and DHFR gene sequencings were performed to detect SMX-TMP resistance. Results Of 54 subjects, 12 had definite PCP, 7 had probable PCP, and 35 were non-PCP. In the PCP cohort, 10 (53%) had HIV infections. Using a cutoff value of ≥ 1.94 copies/µL, the ddPCR exhibited an overall sensitivity of 91.7% (61.5-99.8%) and specificity of 88.1% (74.4-96%). It showed a better performance when different cutoff values were used in subjects with HIV (≥ 1.80 copies/µL) and non-HIV (≥ 4.5 copies/µL). ROC curves demonstrated an AUC of 0.80 (95% CI, 0.56-1.0) for the HIV group, and 0.99 (95% CI, 0.95-1.0) for the non-HIV group. Of 16 PCP samples tested for DHPS- and DHFR-mutations, only DHPS mutations were detected (2). Most of the subjects, including those with DHPS mutations, demonstrated favorable outcomes. Conclusions The ddPCR exhibited a satisfactory diagnostic performance for PCP. Based on very limited data, the treatment outcomes of PCP did not seem to be affected by the DHPS mutations.

Topics: Adult; Dihydropteroate Synthase; HIV Infections; Humans; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

In recent years, there has been an increasing incidence of Pneumocystis jirovecci pneumonia(PCP)in immunosuppressed non-HIV patients. However, only a few studies on PCP developed during chemotherapy for gastrointestinal cancer have been reported. Case 1: A 72-year-old man was complaining of dyspnea during chemotherapy for unresectable gastric cancer. The patient showed high β-D-glucan levels, and his sputum tested positive for sputum Pneumocystis PCR. Even after TMP-SMX administration, the patient's respiratory condition worsened; hence, intubation was needed. Finally, he died without showing any improvement. Case 2: A 75-year-old man underwent chemotherapy for a recurrence of cecal cancer and received steroid pulse for adverse events of optic neuritis. However, his respiratory condition worsened. Furthermore, his sputum tested positive for Pneumocystis PCR. Intensive care including TMP-SMX administration followed to improve his condition.. PCP with non-HIV has a more acute onset and a poorer prognosis than that with HIV. It is necessary to identify PCP when there is a rapid progression of respiratory symptoms and pneumonia in cancer patients undergoing chemotherapy or steroid treatment.

Topics: Aged; Gastrointestinal Neoplasms; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Autoimmune Diseases; Contraindications, Drug; Drug Therapy, Combination; Female; Humans; Leukopenia; Liver; Male; Methotrexate; Middle Aged; Pneumonia, Pneumocystis; Transaminases; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is an opportunistic pathogen that may cause severe, life-threatening respiratory infections in immunocompromised patients such as those with kidney transplants. Although antimicrobial prophylaxis is now universally recommended in the early post-transplant period, Pneumocystis pneumonia (PCP) can occur later. If such infection occurs, mortality rates are high. Beyond standard therapy with trimethoprim-sulfamethoxazole, there is a lack of evidence-based options for intensifying treatment when initial therapy fails to show improvement. Moreover, it is usual to minimize immunosuppression in life-threatening infection, but graft damage may occur, particularly in kidney transplant recipients at above-average immunological risk. Here we present two cases of severe PCP in high immunological risk recipients who were managed with adjunctive intravenous immunoglobulin and withdrawal of immunosuppression. Both patients recovered and were discharged from hospital with functioning grafts.

Topics: Humans; Immunoglobulins, Intravenous; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia is a common opportunistic infection in kidney transplant recipients caused by the ascomycetous fungi Pneumocystis jirovecii. Its clinical presentation of a progressive nonproductive cough, shortness of breath, and fever is nonspecific and often delays diagnosis and appropriate treatment. Moreover, the plain radiograph may show a spectrum of findings from normal to bilateral diffuse infiltrates. Detection of serum (1,3)-β-D-glucan along with consistent clinical findings can be used as early screening tools to diagnose and initiate treatment for Pneumocystis pneumonia pending confirmation by bronchoscopy.. This case series describes 6 kidney transplant recipients who were diagnosed as having Pneumocystis pneumonia. The baseline demographic variables, presenting symptoms, radiographic findings, laboratory findings including lactate dehydrogenase and serum (1,3)-β-D-glucan levels, bronchoscopy findings, and its timing in relation to a positive serum (1,3)-β-D-glucan test, and response to treatment were collected.. All 6 patients who completed the first 3 months of prophylaxis against Pneumocystis pneumonia with sulfamethoxazole-trimethoprim were diagnosed as having Pneumocystis pneumonia between 2 to 24 years post transplant. They initiated treatment early based on a positive serum (1,3)-β-D-glucan and negative Histoplasma antigen and serum galactomannan test with a presumptive diagnosis of Pneumocystis pneumonia, which was later confirmed with a positive polymerase chain reaction on bronchoalveolar lavage fluid.. Pneumocystis pneumonia is a common opportunistic fungal infection in immunosuppressed kidney transplant recipients, and use of serum (1,3)-β-D-glucan can be used as an initial screening test for its early diagnosis and treatment.

Topics: Adult; Aged; Diagnosis, Differential; Female; Humans; Immunocompromised Host; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Complications; Proteoglycans; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Anti-melanoma differentiation-associated gene 5 juvenile dermatomyositis (anti-MDA5 JDM) is associated with high risk of developing rapidly progressive interstitial lung disease (RP-ILD). Here we report an 11-year-old girl with anti-MDA5 JDM and RP-ILD which led to a fatal outcome, further aggravated by SARS-CoV-2 infection. She was referred to our hospital after being diagnosed with anti-MDA5 JDM and respiratory failure due to RP-ILD. On admission, fibrobronchoscopy with bronchoalveolar lavage (BAL) revealed

Topics: Adenosine Monophosphate; Alanine; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antiviral Agents; Autoantibodies; Bronchoscopy; Child; COVID-19; COVID-19 Nucleic Acid Testing; Cyclophosphamide; Dermatomyositis; Disease Progression; Fatal Outcome; Female; Humans; Hydroxychloroquine; Immunocompromised Host; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Interferon-Induced Helicase, IFIH1; Lung; Lung Diseases, Interstitial; Lymphohistiocytosis, Hemophagocytic; Mediastinal Emphysema; Methylprednisolone; Piperidines; Pneumonia, Pneumocystis; Pneumothorax; Pyrimidines; Respiratory Insufficiency; Shock, Septic; Subcutaneous Emphysema; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Humans; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PJP) is a significant cause of morbidity and mortality in transplant patients yet little is known about their adherence to prophylaxis. The goal of this study was to evaluate patient uptake and long-term adherence after implementing universal, lifelong PJP prophylaxis.. This retrospective cohort study evaluated an adult kidney transplant program 18-months after initiating trimethoprim-sulfamethoxazole (TMP-SMX) 80/400 mg thrice-weekly following a cluster of PJP cases. The protocol incorporated multi-modal patient education and drug tolerability strategies to improve adherence, including a modified re-challenge strategy for TMP-SMX intolerance. Adherence was independently confirmed by the transplant pharmacist and nurse for each patient, with an a priori target ≥ 75% population on prophylaxis.. Initial uptake was high with 237/250 (94.8%) patients starting prophylaxis. Long-term maintenance was high with 192/237 (81.0%) patients remaining on prophylaxis at 18-months. Of the remaining 45 patients who initiated prophylaxis, 36/237 (15.2%) were non-adherent and 9/237 (3.8%) discontinued prophylaxis by 18-months. Reasons for non-adherence included gastrointestinal upset, fear of drug reactions and cost; but the majority of reasons were not delineated by the patients (31/36, 86.1%). There was a statistically significant increase in serum creatinine 3.3 µmol/L (0.3-6.3 µmol/L 95% CI) and potassium 0.08 mmol/L (0.03-0.15 mmol/L 95% CI) in those prescribed TMP-SMX with only 3/237 (1.3%) patients discontinuing TMP-SMX for an increase in creatinine.. High rates of patient uptake (94.8%) and long-term adherence (81.0%) were observed after implementing universal lifelong PJP prophylaxis. This may be due in part to the in-depth patient education and drug tolerability strategies employed.

Topics: Adult; Humans; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Anti-Pneumocystis pneumonia (PCP) prophylaxis is recommended for 3 to 6 months post-transplant in HIV-negative kidney transplant recipients. For HIV-positive kidney transplant recipients, there is no definite duration of primary prophylaxis and is often prescribed life-long. The objective of this study was to determine the incidence of PCP in HIV-positive recipients who received 6 months of prophylaxis with trimethoprim-sulfamethoxazole or an alternative agent. One hundred and twenty-two HIV-positive recipients received a kidney transplant from 2001 to 2017 at Hahnemann University Hospital. Most patients received induction immunosuppression with an IL-2 receptor antagonist, with or without intravenous immunoglobulin. Only one patient received anti-thymocyte globulin. Maintenance immunosuppression included a calcineurin-inhibitor (tacrolimus or cyclosporine), an antiproliferative agent (mycophenolate or sirolimus), and prednisone. Mean CD4 cell count was 461 ± 127 cells/uL prior to transplant and 463 ± 229 cells/μL at 6 to 12 months after transplant. None of the recipients developed PCP after a median follow-up of 2.88 years (IQR 1.16-4.87). Based on our observation, a 6-month regimen of PCP prophylaxis may be sufficient among HIV-positive recipients, similar to those without HIV infection.

Topics: HIV Infections; Humans; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

The effectiveness of trimethoprim/sulfamethoxazole (TMP/SMZ) for pneumocystis pneumonia (PCP) is limited with adverse events. Caspofungin, by inhibiting the cyst form of Pneumocystis jirovecii, may be an alternative therapy for PCP. However, the availability of clinical data about caspofungin combined with TMP/SMZ in the treatment of PCP in HIV-infected patients is limited. Thus, we aimed to examine the clinical effectiveness and safety of caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in HIV-infected patients.. From January 2017 to December 2019, data of HIV-infected patients with moderate-to-severe PCP who received either TMP/SMZ alone or caspofungin combined with TMP/SMZ as first-line therapy were retrospectively reviewed to assess the effectiveness and safety of each regimen. The Kaplan-Meier curve and log-rank test were used for survival analysis.. A total of 278 patients met the criteria. The overall positive response rate of PCP treatment was 48.92%, and the overall all-cause in-hospital mortality rate was 33.09%. Patients who received combination therapy consisting of caspofungin and TMP/SMZ had a better positive response rate (59.44% vs. 37.78%, P < 0.001) and lower all-cause in-hospital mortality rate (24.48% vs. 42.22%, P = 0.003). Also, patients who received combination therapy had higher survival rate during a hospital stay (75.52% vs. 57.78%, P = 0.004), and those who received longer combination therapy were more likely to have higher survival rate (P = 0.042). We found that age (P = 0.019), CD4 cell count (P = 0.001) and therapeutic regimen (P = 0.002) were significant risk factors for all-cause in-hospital mortality rate in univariate analysis. In multivariate analysis, only CD4 cell count and therapeutic regimen were statistically significant factors associated with all-cause in-hospital mortality rate. Patients with a CD4 count of > 30 cells/µL and patients who received combination therapy consisting of caspofungin and TMP/SMZ were more likely to survive from PCP (P = 0.011 and P = 0.002, respectively). There were no additional severe adverse events caused by adding caspofungin.. For HIV-infected patients with moderate-to-severe PCP, combination therapy with caspofungin and TMP/SMZ is an effective and promising first-line therapy with no greater number of adverse events compared with TMP/SMZ monotherapy. Patients who received caspofungin had better positive response rates and lower all-cause in-hospital mortality rates. Also, we recommend early initiation of caspofungin.

Topics: Caspofungin; HIV Infections; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Dapone and atovaquone are therapeutic options for PJP prophylaxis in renal transplant recipients. The objective of this study was to evaluate the incidence of anemia in renal transplant recipients receiving these agents.. This is an IRB-approved, retrospective analysis of adult renal transplant recipients who received either dapsone or atovaquone. The primary endpoint was the change in hemoglobin within 90 days of drug initiation. Other endpoints of interest included incidence and management of anemia at multiple time points post-transplant. Categorical variables were compared with Pearson's chi-squared or Fischer's exact test and continuous data were compared utilizing Wilcoxon rank-sum test. Statistical analyses were performed using Stata 14.2.. A total of 478 patients were screened for inclusion; 50 patients were evaluated in both the dapsone and atovaquone groups. In the dapsone and atovaquone groups, the median age was 52 and 50.5 years, 44% and 42% were Caucasian, and median time to treatment initiation was 27 and 39 days post-transplant, respectively. All patients receiving dapsone had normal G6PD function. There was no difference in baseline hemoglobin between groups (9.7 g/dL vs 9.8 g/dL, P = .83). The median nadir hemoglobin values were 8.6 g/dL and 9.6 g/dL in the dapsone and atovaquone groups, respectively (P = .047). The median decrease in hemoglobin from baseline to nadir was 1.3 g/dL in dapsone patients and 0.2 g/dL in atovaquone patients (P = .001). Dapsone was discontinued in 46% of patients, whereas atovaquone was discontinued in 18% (P = .001).. Among renal transplant recipients with normal G6PD activity, dapsone is associated with greater hemoglobin reductions and rates of drug discontinuation as compared to atovaquone.

Topics: Anemia; Humans; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection among solid organ transplantation. The occurrence of PJP is dangerous and fatal if there is no early identification and sufficient treatment.. The aim of this study was to evaluate the risk factors and provide appropriate strategies of prophylaxis and treatment for PJP after kidney transplantation in our centre.. From January 2009 to December 2018, a total of 167 kidney transplantation recipients with pneumonia were enrolled, including 47 PJP patients as PJP group and 120 non-PJP patients as control group. The clinical characteristics of the two groups were analysed retrospectively.. Multivariate analysis showed that high total dosage of ATG [OR, 2.03; 95% CI, 1.12-3.68] and cytomegalovirus (CMV) infection were independent risk factors for PJP. Trimethoprim-sulfamethoxazole (TMP-SMX) (1.44 g q6h)-based treatment was used for 2 weeks, and its dosage and course were adjusted according to the therapeutic effect and side effects. Forty-five cases were recovered after 3 months of follow-up, and two patients died of respiratory failure. TMP-SMX (0.48 g/day) prophylaxis was used for 3-6 months and prolonged to 7-8 months after treatment for acute rejection, which reduced the incidence of PJP compared with those without prophylaxis.. Our study suggests that the high total dosage of ATG and CMV infection indicate the increased risk of PJP. The strategies of prophylaxis and treatment for PJP after kidney transplantation in our centre were effective.

Topics: Adult; Antibiotic Prophylaxis; Antilymphocyte Serum; Cytomegalovirus Infections; Female; Humans; Immunosuppression Therapy; Incidence; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Transplant Recipients; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Clinicians should be aware of the risk of opportunistic infections in patients who are immunocompromised. Opportunistic infections such as Pneumocystis jirovecii commonly are associated with HIV/AIDS, but less commonly considered in patients receiving immunosuppressive and/or immunomodulating therapies. This case report focuses on the management of an opportunistic infection in an HIV-negative patient on immunosuppressive medications for lymphoma and exacerbation of pulmonary fibrosis.

Topics: Aged; Anti-Bacterial Agents; Bendamustine Hydrochloride; HIV Seronegativity; Humans; Immunocompromised Host; Lung Diseases, Interstitial; Lymphoma, Mantle-Cell; Male; Opportunistic Infections; Pneumonia, Pneumocystis; Prednisone; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) combination is used for the prophylaxis of Pneumocystis pneumonia (PCP). Although TMP/SMX is frequently used in dermatology for cases treated with corticosteroids and/or immunosuppressants, it is often difficult to continue the administration of TMP/SMX due to adverse events. There are only a few reported studies on the prophylaxis of PCP in dermatology. This is the first review focused on adverse events of TMP/SMX among patients with dermatological diseases compared with previous reports. In this study, we retrospectively investigated 132 cases treated with TMP/SMX and examined the adverse events. Adverse events occurred in 32 cases (24.2%) and the incidence in this study was higher than in previous reports. Thrombocytopenia occurred in 17 cases (12.5%), which was the most frequent adverse event. The possible causes of adverse events were that the standard dose of TMP/SMX may be excessive for most Japanese, in addition to the long administration period, and the concomitant use of corticosteroids and/or immunosuppressants in almost all cases. We must consider the risks of PCP and adverse events of TMP/SMX in each case. It is desirable to examine possible administration methods that can be continued by adjusting the dose and interval of TMP/SMX.

Topics: Antibiotic Prophylaxis; Dermatology; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

A 75-year-old man was treated with bendamustine-containing chemotherapy for follicular lymphoma. Trimethoprim-sulfamethoxazole (TMP-SMX) for pneumocystis pneumonia (PCP) prophylaxis was discontinued at the last course of the chemotherapy. However, the patient developed PCP 6 months after the last course, and treatment with TMP-SMX (480 mg/day) was initiated. The TMP-SMX dose was reduced after 3 weeks of treatment. However, PCP recurred 6 days after dose reduction. Increasing the TMP-SMX dose to the therapeutic dose improved PCP. The dose was reduced to a maintenance dose after 7 weeks of the therapeutic dose of TMP-SMX treatment, and PCP did not recur thereafter. This case demonstrated that the early recurrence of PCP after appropriate treatment duration in immunocompromised conditions after chemotherapy, including bendamustine, may require prolonged treatment.

Topics: Aged; Humans; Lymphoma, Follicular; Male; Neoplasm Recurrence, Local; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The use of trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis pneumonia (PcP) prophylaxis is often discontinued owing to adverse drug reactions. Half-dosage of TMP-SMX (40/200 mg daily) is considered more tolerable than the conventional dosage (80/400 mg daily). However, patient background characteristics that are associated with the discontinuation of TMP-SMX prophylaxis and suitable for reduced dosage remain unclear. In this study, we aimed to identify the risk factors for the discontinuation of and efficacy of different doses of TMP-SMX prophylaxis in patients with creatinine clearance higher than 30 mL/min.. We retrospectively evaluated 318 immunocompromised non-human immunodeficiency virus (HIV)-infected patients (194 men and 124 women; median age, 68.5 [interquartile range, 59-75] years) who underwent TMP-SMX therapy as a primary PcP prophylaxis between July 2014 and August 2019. The patients were segregated into two groups on the basis of dosage: single-strength (SS; n = 244) and half-strength (HS; n = 74) groups. We evaluated PcP occurrence, TMP-SMX discontinuation rate, and discontinuation-related risk factors in these groups.. PcP did not occur in either group. The univariate and multivariate Cox proportional hazards models revealed that the SS dosage and renal function (e.g. serum creatinine and creatinine clearance) were independently associated with prophylaxis discontinuation. At 24 weeks, the HS group presented significantly lower discontinuation rates than the SS group (P = 0.019, log-rank test). In the SS group, patients with mild renal impairment (e.g. serum creatinine ≥0.78 mg/dL or creatinine clearance ≤64.26 mL/min) presented significantly higher TMP-SMX discontinuation rates than those without such an impairment (P < 0.05, log-rank test with Bonferroni correction). This difference was not significant in the HS group.. Mild renal impairment might increase the risk of discontinuation of conventional TMP-SMX prophylaxis. In patients with a mild renal impairment, the HS dosage may improve tolerability while maintaining prophylactic efficacy.

Topics: Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

An 82-year-old woman treated for advanced lung cancer with gefitinb was admitted to the emergency unit complaining of dyspnea. Chest computed tomography found abnormalities classified as possible diffuse COVID-19 pneumonia. RT-PCR for Sars-Cov-2 was twice negative. PCR for Pneumocystis jirovecii was positive on bronchoalveolar lavage. The final diagnosis was Pneumocystis jirovecii pneumonia. Therefore, physicians must be careful not to misdiagnose COVID-19, especially in cancer patients on small-molecule therapeutics like gefitinib and corticosteroids.

Topics: Aged, 80 and over; Antineoplastic Agents; COVID-19; Diagnostic Errors; Female; Gefitinib; Humans; Lung Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; SARS-CoV-2; Trimethoprim, Sulfamethoxazole Drug Combination

Prospective collection of clinical information for all suspected and proven cases of PJP in children with cancer in the UK and Ireland.. A surveillance survey was undertaken using a key contact at each paediatric oncology Principle Treatment Centre (PTC).. To describe the mortality, outcomes and use of prophylaxis in this at-risk group.. The study confirms that PJP is rare, with only 32 cases detected in the UK over a 2-year period reported from all 20 PTCs. No deaths were directly attributed to PJP, in contrast to previously reported high mortality rates. Breakthrough infection may occur despite prescription of ostensibly adequate prophylaxis with co-trimoxazole; 11 such cases were identified. Six infections occurred in patients for whom prophylaxis was not thought to be indicated. Two infections occurred in patients for whom prophylaxis was specifically omitted due to concerns about potential bone marrow suppression or delayed engraftment.. PJP in children treated for malignant disease is rare. Breakthrough infection despite prophylaxis with co-trimoxazole may represent pathogen resistance or non-compliance. Further consideration of the use of PJP prophylaxis during acute myeloid leukaemia and non-Hodgkin's lymphoma treatment is warranted, alongside appraisal of the clinical implications of the possible marrow suppressive effects of co-trimoxazole and its interactions with methotrexate.

Topics: Adolescent; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antimetabolites, Antineoplastic; Child; Child, Preschool; Humans; Incidence; Infant; Ireland; Methotrexate; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Population Surveillance; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; United Kingdom

To investigate short-term prognosis and prognostic factors for connective tissue disease-associated pneumocystis pneumonia (CTD-PCP) using the Japanese nationwide diagnosis procedure combination (DPC) inpatient database.. The present retrospective cohort study from April 2014 to March 2016 included data of patients with CTD-PCP extracted from the DPC database using the 10. In 15 901 766 cases registered from 1329 hospitals, 333 of 67 890 patients who were admitted with PCP were diagnosed with CTD-PCP and included in the study. The median age was 71.0 years, and 214 (64.3%), 80 (24.0%), and 29 (8.7%) patients received sulfamethoxazole/trimethoprim (ST) monotherapy and pentamidine-containing and atovaquone-containing therapy, respectively. There were 114 (34.2%) in-hospital deaths, and the 30-day and 60-day in-hospital survival rates after PCP treatment initiation were 66.0% and 53.7%, respectively. Older age (HR 1.06, 95% CI 1.03 to 1.08) and concomitant interstitial lung disease (ILD) (HR 1.65, 95% CI 1.12 to 2.42) were poor prognostic factors. Patients who completed PCP treatment with ST monotherapy had a significantly higher survival rate than those treated with those not treated with ST monotherapy (p=0.015; log-rank test). Pentamidine versus atovaquone as second-line therapy was significantly higher with atovaquone (p=0.012; log-rank test).. Older age and concomitant ILD were poor prognostic factors for CTD-PCP. ST was a reasonable first-line therapy in patients with CTD-PCP, and patients with inadequate response to ST treated with atovaquone tended to have a better prognosis than those treated with pentamidine.

Topics: Aged; Connective Tissue Diseases; Humans; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Prophylaxis of Pneumocystis jiroveci pneumonia (PJP) with trimethoprim/sulfamethoxazole is a standard of care for children with hematologic malignancies, while its use in solid tumor patients is still debated. A retrospective study focusing on the use of PJP prophylaxis in patients with solid tumors was performed among 16 AIEOP centers: 1046/2863 patients did not receive prophylaxis and no cases of PJP were reported.

Topics: Adolescent; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Agents; Child; Child, Preschool; Humans; Immunocompromised Host; Neoplasms; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Kidney Injury; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Crystallization; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination; Urinalysis; Urine

A 36-year-old African American man with no medical history presented with a recent history of cough and dyspnoea. Initial chest imaging revealed diffuse bilateral lung infiltrates. A subsequent HIV test resulted positive, and he was presumptively diagnosed with AIDS, later confirmed by a CD4 of 88 cells/mm

Topics: Acquired Immunodeficiency Syndrome; Adult; Antiretroviral Therapy, Highly Active; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Sarcoma, Kaposi; Trimethoprim, Sulfamethoxazole Drug Combination

 A 68-year-old male patient with psorias and a bullous pemphigoid as an underlying disease developed bilateral groundglass opacities on chest CT under longer-term, higher-dose immunosuppressive therapy with methylprednisolone with clinical symptoms of dry cough, progressive dyspnea and fever..  After the exclusion of COVID-19, Pneumocystis jirovecii pneumonia (PCP) was detected and a corresponding high-dose therapy with trimethoprim-sulfamethoxazole was initiated promptly..  Nonetheless, a complicated course with bacterial superinfection and pulmonary aspergillosis as well as ARDS developed..  In contrast to COVID-19, the typical course, diagnosis and therapy of Pneumocystitis jirovecii pneumonia are discussed. It is particularly emphasized that not all ground glass infiltrates in the CT chest image can be traced back to a COVID-19, even in a pandemic situation. Possible differential diagnoses should always be considered and taken into account in the diagnosis..  Ein 68 Jahre alter männlicher Patient mit einer Psoriasis und einem bullösen Pemphigoid als Grunderkrankungen entwickelte unter einer länger anhaltenden, höher dosierten immunsuppressiven Therapie mit Methylprednisolon eine klinische Beschwerdesymptomatik mit trockenem Reizhusten, einer progredienten Dyspnoe und Fieber..  Im CT-Thorax zeigten sich beidseitige Milchglasinfiltrate. Nach Ausschluss von COVID-19 wurde eine Pneumocystis-jirovecii-Pneumonie (PCP) nachgewiesen..  Es wurde daraufhin eine entsprechende hochdosierte Therapie mit Trimethoprim-Sulfamethoxazol zeitnah eingeleitet. Gleichwohl entwickelte sich ein komplizierter Verlauf mit bakterieller Superinfektion und pulmonaler Aspergillose sowie ARDS.  DISKUSSION UND FOLGERUNG:  In Abgrenzung zu COVID-19 werden der typische Verlauf sowie Diagnostik und Therapie der Pneumocystis-jirovecii-Pneumonie diskutiert. Es wird insbesondere darauf abgehoben, dass auch in einer Pandemiesituation nicht alle Milchglasinfiltrate im CT-Thorax-Bild auf COVID-19 zurückzuführen sind. Mögliche Differenzialdiagnosen sollten stets bedacht und in der Diagnostik berücksichtigt werden.

Topics: Aged; Antifungal Agents; COVID-19; Diagnosis, Differential; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

It is hard for clinicians to choose the best regimen for pneumocystis jirovecii pneumonia (PJP) prophylaxis. The aim is to evaluate the effectiveness and safety of thrice weekly double strength (TWDS) vs daily single strength (DSS) trimethoprim-sulfamethoxazole (TMP-SMX) for prophylaxis of PJP after kidney transplantation.. Adult renal transplant recipients (RTRs) who were transplanted between January 1, 2015 and July 1, 2018 were evaluated. A total of 189 RTRs were prescribed PJP prophylactic regimen during the study period (TWDS group: n=98; DSS group: n=91).. Morbidity due to PJP infection was significantly higher in TWDS group as compared with DSS group (8.60% vs 1.14%, p= 0.021). There was a significant trend toward higher prevalence of confirmed PJP (log-rank=0.021) in TWDS group. The use of DDS TMP-SMX for prophylaxis after kidney transplantation was associated with a 79% reduction in the incidence of PJP comparing the prophylactic regimen of TWDS. There was no significant difference between the two groups in the overall rate of premature TMP-SMX discontinuation and laboratory indexes.. Six months of DSS TMP-SMX prophylaxis was more effective than TWDS TMP-SMX regimen with the same safety profile.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Drug Administration Schedule; Female; Humans; Kidney Transplantation; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia (PCP) is a life-threatening pulmonary infection after kidney transplantation (KTx). Its onset in the current era of modern immunosuppression and of routine use of universal PCP prophylaxis seems to differ from its onset in previous decades in terms of late onset with subtle clinical presentation, indicating a need for increased vigilance.. We retrospectively studied all KTx recipients from our center who underwent bronchoscopy and bronchoalveolar lavage (BAL) between 2009 and 2018. Of these, all cases with confirmed PCP any time after the first post-KTx year were included in the analysis.. Among 60 patients with KTx who had undergone bronchoscopy and BAL, 12 cases with late-onset PCP were identified. PCP appeared late at a median of 10.8 (interquartile range, 2.4-15.8) years after transplantation. Patients' mean age was 59 years, and all were receiving stable low-dose immunosuppression. Most of the patients (67%) had received PCP prophylaxis after KTx. Five out of 12 patients (42%) had concomitant cytomegalovirus (CMV) reactivation at the time of PCP. In almost all cases, clinical presentation was mild. Treatment consisted of trimethoprim-sulfamethoxazole (TMP-SMX) and intravenous corticosteroid administration, and concomitant immunosuppression was temporarily reduced or withdrawn. Outcome was generally good. None of the patients developed respiratory insufficiency or required mechanical ventilation. One patient died as a result of sepsis, and 3 more with preexisting advanced chronic kidney disease subsequently lost their grafts.. Renal transplant recipients are at risk of late-onset PCP, even at a steady state of low-dose maintenance immunosuppression. Because of its subtle clinical presentation, high suspicion of the disease is warranted. Its early recognition and proper management are essential for a successful outcome.

Topics: Adult; Aged; Female; Humans; Immunosuppression Therapy; Kidney Transplantation; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Complications; Retrospective Studies; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Little is known regarding the optimal management of nocardiosis among solid organ transplant (SOT) recipients. It is often suggested to avoid trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy in heavily immunocompromised patients (such as SOT recipients) and/or in case of severe or disseminated nocardiosis. Our aim was to report our experience with TMP-SMX monotherapy in SOT recipients with nocardiosis.. Using data from a previously published European study, we assessed the incidence of adverse events in SOT recipients receiving TMP-SMX monotherapy and assessed its effectiveness.. Thirty-one SOT recipients with nocardiosis were included, mostly kidney transplant recipients (20/31, 65%). Eleven (36%) had disseminated infection, and four (13%) had brain nocardiosis. Most patients had lung and/or pleural involvement (26/31, 84%). Daily dose of trimethoprim at initiation was 10 [6.4-14.8] mg/kg. The median estimated glomerular filtration rate at time of diagnosis of nocardiosis was 44 [30-62] ml/min/1.73 m². TMP-SMX was discontinued prematurely in one third of the patients (10/31, 32%, mostly for hematological toxicity [n = 3] or increased serum creatinine [n = 3]). Focusing on the 24 (77%) patients who completed at least 30 days of TMP-SMX monotherapy, 4 had late (>30 days) drug discontinuation, 1 experienced treatment failure, and 19 completed planned TMP-SMX monotherapy. Clinical outcome was favorable in these 19 patients, despite the fact that 8 (42%) had disseminated infection and 2 (11%) brain nocardiosis. Overall, all-cause 1-year mortality was 10% (3/31).. TMP-SMX monotherapy appears to be effective for the treatment of most nocardiosis among SOT recipients. Interventional studies are needed to compare its safety and effectiveness with those of other regimens used to treat posttransplant nocardiosis.

Topics: Humans; Nocardia Infections; Organ Transplantation; Pneumonia, Pneumocystis; Retrospective Studies; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is a potentially life-threatening infection. Trimethoprim-sulfamethoxazole (TMP-SMX) is considered as the first regimen for PCP prophylaxis according to several guidelines. The recommended prophylactic dose of TMP-SMX has been determined based on patients with normal renal function, but the appropriate dosage for patients undergoing hemodialysis is unknown. The aim of this study was to investigate the efficacy and safety of low-dose TMP-SMX in patients undergoing hemodialysis.. HIV-uninfected adult patients who were undergoing hemodialysis and administered TMP-SMX for PCP prophylaxis, were included, and divided into standard-dose (≥6 single strength (SS, TMP-SMX 80 mg/400 mg tablets/week) and low-dose groups (< 6 SS tablets/week). The endpoints were cumulative incidence of PCP and cumulative discontinuation rate of TMP-SMX due to adverse events. For comparison of the groups, we employed the chi-squared test for categorical variables and the Mann-Whitney U test for continuous variables. Risk factors for the endpoints were evaluated using the Cox Fine and Gray method.. The median age of the 81 patients included in the study was 67 years (IQR: 60-76 years), and 52 patients (64.2%) were men. No patients in either group developed PCP during the observation period. The yearly cumulative incidence of discontinuation was 12.1% (95% confidence interval [CI]: 0.027-0.29) in the low-dose group and 35.6% (95% CI: 0.20-0.52) in the standard-dose group (P = 0.019). The adjusted hazard ratio of the low-dose group compared to standard-dose group was 0.18 (95% CI: 0.04-0.86, P = 0.032).. None of the study patients developed PCP, and the cumulative discontinuation rate of TMP-SMX due to adverse events was significantly lower in the low-dose group compared to that in the standard-dose group (P = 0.032). These results indicate that low-dose TMP-SMX is an appropriate regimen to maintain a balance between PCP prophylaxis and prevention of adverse events due to TMP-SMX administration. These findings can guide health care professionals to determine TMP-SMX dosage when considering PCP prophylaxis for patients undergoing hemodialysis.

Topics: Aged; Anti-Infective Agents, Urinary; Antibiotic Prophylaxis; Dose-Response Relationship, Drug; Female; Humans; Incidence; Male; Middle Aged; Pneumonia, Pneumocystis; Renal Dialysis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Lung cancer is the leading cause of cancer death. Radiotherapy given in the curative setting is associated with a 3% risk of death from Pneumocystis jirovecii pneumonia (PJP). Prolonged courses of high-dose steroids also increase the risk of PJP. International guidelines recommend the use of chemoprophylaxis with trimethoprim-sulfamethoxazole for patients at high risk. We assessed the effect of an intervention designed to reduce the impact of PJP.. Prophylaxis guidelines were introduced in 2016. Case records of patients treated with radical radiotherapy were examined for the periods 2014 to 2015 (pre-intervention) and 2017 to 2018 (post-intervention). In total, 247 patients were treated pre-intervention and 334 post-intervention.. Freedom from PJP death at 1 year was 96% before intervention and 99% after (hazard ratio 0.3, 95% confidence interval 0.1-0.9, P = 0.029). Although the rate of use of chemoprophylaxis according to the guideline rose from 1% to 13% (P = 0.003), the use of high-dose steroids also fell from 35% to 16% (P < 0.00001).. Reducing radiotherapy-associated infections is an important component of radical treatment in lung cancer. Highlighting chemoprophylaxis guidelines reduced the death rate from PJP, with an associated more judicious use of steroids. Advocating prophylaxis in patients with lymphocyte count <0.6 × 109/l is the next intervention to be studied.

Topics: Humans; Immunocompromised Host; Lung; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX), a prophylactic agent against pneumocystis pneumonia (PCP), can cause adverse drug reactions (ADRs), particularly in patients with systemic lupus erythematosus (SLE). However, the risk factors for ADRs remain unclear. Thus, we sought to examine the prevalence of TMP-SMX-related ADRs in patients with SLE and identify specific risk factors for ADR development in these patients.. We retrospectively reviewed data from patients with connective tissue disease (CTD) who were administered TMP-SMX as a PCP prophylactic. The prevalence of ADRs was compared between patients with SLE and those with other CTDs. Univariate and multivariate analyses were conducted to identify risk factors for ADRs in patients with SLE.. Of the 424 patients with CTD included in our study (SLE, n = 162; other CTDs, n = 262), 22 with SLE (13.6%) developed ADRs, and this rate was significantly higher than that observed in patients with non-SLE CTDs (n = 18 [6.9%], p = 0.033). In patients with SLE, univariate analyses revealed direct associations of ADRs with anti-Sm (p < 0.001), anti-RNP (p = 0.02), and anti-Ro/SS-A antibodies (p = 0.042). Multivariate analysis identified a significant association between anti-Sm antibody levels and the development of ADRs (adjusted odds ratio 5.27, 95% confidence interval 1.80-15.40, p = 0.002).. Patients with SLE who are prophylactically administered TMP-SMX are at high risk of ADRs. Among these patients, those who display a positive anti-Sm antibody should be carefully monitored for ADRs.

Topics: Connective Tissue Diseases; Drug-Related Side Effects and Adverse Reactions; Humans; Lupus Erythematosus, Systemic; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Opportunistic infection with multiple pathogens currently has become less uncommon since the application of immunosuppressant or corticosteroid in non- Human immunodeficiency virus patients. However, the clinical diagnosis of the co-infection remains difficult since the uncertainty and deficiency of the microbiologic testing methods.. A 66-year-old male patient was admitted to our hospital with chest stuffiness, shortness of breath and elevated body temperature.. He was diagnosed with the co-infection of Pneumocystis jiroveci and cytomegalovirus by metagenomic next-generation sequencing of bronchoalveolar lavage fluid after bronchoscopy.. The patient was empirically treated with broad-spectrum antibiotics, trimethoprim/ sulfamethoxazole and ganciclovir in the beginning of the admission.. The condition of this patient was not improved even with the intervention at the early stage of the disease. His family requested discharge after 24 inpatient days.. This case highlights the application of metagenomic next-generation sequencing in the clinical diagnosis of pulmonary co-infection. Suitable prophylaxis, necessary clinical awareness and accurate diagnosis are indispensable for immunocompromised patients with pulmonary infection.

Topics: Aged; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Bronchoscopy; Coinfection; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; High-Throughput Nucleotide Sequencing; Humans; Male; Metagenomics; Methylprednisolone; Nephrotic Syndrome; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Hematopoietic cell transplantation (HCT) offers long-term cure against early morbidity and mortality of hemoglobinopathies, such as sickle cell disease (SCD) and beta-thalassemia. Following HCT, sirolimus is an immunosuppressant used to prevent graft-versus-host disease (GVHD) while receiving trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jirovecii prophylaxis and other antimicrobial agents (including acyclovir). One rare adverse event associated with both drugs is rhabdomyolysis, defined as creatine kinase (CK) elevation at least 5 to 10 times the upper limit of normal. This study was conducted to evaluate the rate of and risk factors for developing rhabdomyolysis in the post-HCT setting. Across 4 haploidentical and matched related donor (MRD) nonmyeloablative protocols, CK levels were prospectively monitored and patients were retrospectively identified for rhabdomyolysis. The rhabdomyolysis was graded based on the severity of CK elevation and other organ injury. At diagnosis, patients were queried for concurrent medication use (ie, sirolimus, TMP-SMX, acyclovir, or statins), sex, age, donor genotype, and time from transplantation. Among 127 patients with mostly SCD, rhabdomyolysis occurred in 22 (17%), including 2 recipients of haploidentical donor HCT and 20 recipients of MRD HCT. The time to the development of rhabdomyolysis was 61 and 73 days for the 2 recipients of haploidentical HCT and a median of 73 days for the MRD HCT recipients. Among the 22 patients who developed rhabdomyolysis, 20 (91%) were receiving sirolimus (2 haploidentical HCT recipients and 18 MRD HCT recipients), and 14 (64%) were also receiving TMP-SMX (all in the MRD HCT group). Seventy-five percent of the haploidentical donors and 69% of the MRDs had sickle cell trait. All but 2 patients with rhabdomyolysis were male. No patients who developed rhabdomyolysis were receiving statins at any point. Higher-than-expected rates of rhabdomyolysis were found post-transplantation for patients with SCD and beta-thalassemia. Contributing risk factors included immunosuppression with sirolimus, TMP-SMX, male sex, and sickle trait donor. These factors differ from the excessive muscle strain or injury, seizures, infections, or HMG-CoA inhibitors typically identified in non-HCT recipients.

Topics: Hematopoietic Stem Cell Transplantation; Humans; Male; Pneumonia, Pneumocystis; Retrospective Studies; Rhabdomyolysis; Sirolimus; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Antibody Formation; Child; History, 20th Century; Humans; Pediatrics; Pneumonia, Pneumocystis; Poliovirus Vaccine, Oral; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Dapsone; Humans; Pneumonia, Pneumocystis; Skin Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Animals; Anti-Infective Agents; Birds; Dapsone; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Dapsone; Drug Therapy, Combination; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PJP) prophylaxis after pediatric solid organ transplant (SOT) is routinely recommended, but practice varies. Online survey was sent in 2018 to 707 members of the International Pediatric Transplant Association. A total of 105 responded, representing 47 institutions in 18 countries consisting of transplant physicians (66%), transplant surgeons (19%), nurse practitioners (6%), infectious disease physicians (5%), or pharmacists (4%). PJP prophylaxis was reported by 88%, while 12% did not routinely give prophylaxis. The majority not using PJP prophylaxis performed renal transplants (67%) citing low incidence of PJP (62%). Trimethoprim/sulfamethoxazole was first-line agent (95%). PJP prophylaxis for 4-6 months was the most frequent duration following kidney (48%, 27/56), liver (42%, 13/31), and heart (40%, 10/25) transplant. Abdominal multivisceral providers equally gave 10-12 months (47%) or lifelong (47%); most lung transplant providers gave lifelong prophylaxis (85%). Across all organs, 21% provided lifetime prophylaxis. After completion of prophylaxis, 32% do not restart for any reason; majority of the rest would restart for treatment of acute graft rejection. 83% reported no PJP cases in the prior 12 months; 14% reporting 1-5 infections. Only 3% reported a case of PJP infection on prophylaxis; none in SOT. PJP prophylaxis is routinely provided to pediatric SOT patients though practice and duration vary by center and organ type. Durations of 4-6 months were most common for renal, liver, and heart transplant recipients, while 10-12 months or lifelong prophylaxis were commonly reported for abdominal multivisceral recipients and most lung transplant recipients are given lifelong prophylaxis.

Topics: Anti-Infective Agents; Child; Guideline Adherence; Health Care Surveys; Healthcare Disparities; Humans; Organ Transplantation; Pediatrics; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Care; Postoperative Complications; Practice Guidelines as Topic; Practice Patterns, Physicians'; Trimethoprim, Sulfamethoxazole Drug Combination

Once-a-week cotrimoxazole is an effective prophylaxis for pneumocystosis during antineoplastic chemotherapy or autologous stem cell transplant. Following allogeneic stem cell transplant, this schedule is at risk of pneumocystosis or neurotoxoplasmosis, as demonstrated by these case reports. Therefore, a 3-times-a-week schedule must be adopted in these patients.

Topics: Antifungal Agents; Child; Drug Administration Schedule; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

International guidelines for Pneumocystis jirovecii pneumonia (PJP) prevention recommend prophylaxis for ≥6 months following allogeneic hematopoietic cell transplantation, and longer in patients with graft-versus-host disease (GVHD) or on immunosuppressive therapy (IST). These recommendations are based on cohorts of patients who did not routinely receive anti-thymocyte globulin (ATG) for GVHD prophylaxis.. We performed a retrospective chart review of 649 patients, all of whom received ATG as part of GVHD prophylaxis.. The cumulative incidence of definite PJP was 3.52% at both 3 and 5 years (median follow up, 1648 days for survivors). PJP occurred in 13 non-GVHD patients between days 207 and 508, due in part to low CD4 T-cell counts (<200 CD4 T cells/µL). PJP occurred in eight GVHD patients between days 389 and 792, due in part to non-adherence to PJP prophylaxis guidelines (discontinuation of PJP prophylaxis at <3 months after discontinuation of IST). Breakthrough PJP infection was not observed in patients receiving prophylaxis with cotrimoxazole, dapsone or atovaquone, whereas three cases were observed with inhaled pentamidine.. In conclusion, for non-GVHD patients receiving ATG-containing GVHD prophylaxis, 6 months of PJP prophylaxis is inadequate, particularly if the CD4 T-cell count is <200 cells/µL or if there is a high incidence of PJP in the community. For patients with GVHD receiving ATG-containing GVHD prophylaxis, continuing PJP prophylaxis until ≥3 months post-discontinuation of IST is important. Cotrimoxazole, dapsone and atovaquone are preferred over inhaled pentamidine.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antilymphocyte Serum; Atovaquone; CD4 Lymphocyte Count; Dapsone; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Immunosuppression Therapy; Incidence; Lymphopenia; Male; Middle Aged; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Severe alcoholic hepatitis (AH) has a very high mortality rate. Current guidelines recommend oral corticosteroids as first-line agents in individuals with severe AH to reduce short-term mortality. However, systemic corticosteroids have serious adverse effects. In individuals with AH, infection, which is one of the complications of steroid use, can result in serious outcomes, such as acute-on-chronic liver failure. Pneumocystis pneumonia (PCP) is a life-threatening opportunistic infection which may occur when high-dose corticosteroids are prescribed for more than 1 month. Therefore, when high-dose corticosteroids are used, providing PCP prophylaxis is warranted. Although trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for the prophylaxis of PCP, its hepatotoxicity limits its use in patients with severe AH who are on high-dose corticosteroids. Moreover, there is a lack of consensus on which drugs should be used for PCP prophylaxis in individuals with severe AH who are on glucocorticoid treatment. Herein, we report a case of a 43-year-old male with fatal PCP that occurred after the use of corticosteroids for severe AH.. A 43-year-old alcoholic man presented with a hematoma on his right leg. His liver function was poor, and he was he was diagnosed with severe AH and treated with oral corticosteroids for 26 days. After glucocorticoid treatment, he developed a productive cough.. A sputum PCR test was positive for Pneumocystis jirovecii.. He was initially treated with TMP-SMX and required artificial ventilation.. He developed disseminated intravascular coagulation and multi-organ failure, and died 10 days after starting TMP-SMX.. To date, prevention of PCP in individuals with severe AH who are on corticosteroids has been overlooked. This case illustrates the need for prophylaxis of PCP in individuals with severe AH taking corticosteroids.

Topics: Adult; Hepatitis, Alcoholic; Humans; Male; Methylprednisolone; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in kidney transplant recipients (KTRs), and prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is recommended. The aim of this study was to investigate incidence and risk factors for PCP in KTRs after 6-month TMP-SMX prophylaxis.. We conducted a case-control study of patients with PCP who received 6-month PCP prophylaxis with TMP-SMX after kidney transplantation (KT). In cases of rejection, PCP prophylaxis was provided for six additional months after anti-rejection therapy. Cytomegalovirus (CMV) infection was not considered an indication for PCP prophylaxis due to concerns of nephrotoxicity associated with TMP-SMX.. Among 3941 kidney or pancreas-kidney transplant recipients, 67 (1.7%) developed PCP after discontinuing TMP-SMX. A total of 47 patients with KT PCP and 94 controls were included. Duration of PCP prophylaxis was similar between cases and controls (median 6 months, P = .53). In multivariate analysis, rejection (OR 3.9; 95% CI 1.4-11.1) and CMV infection (OR 2.4; 95% CI 1.0-5.8) were independently associated with PCP development after TMP-SMX. Rejection or CMV infection was observed in 70% of patients with PCP. Time to PCP development after rejection (median [IQR] 6 [5-19] months) was slightly shorter than after CMV infection (median [IQR] 9 [5-12] months; P = .18).. Post-prophylaxis PCP occurred in <2% of KTRs, and about two-thirds of these experienced rejection or CMV infection. These data suggest that at least 6 to 9-month additional chemoprophylaxis may be needed to prevent PCP in KTRs with transplant rejection or CMV infection.

Topics: Adult; Antibiotic Prophylaxis; Case-Control Studies; Drug Administration Schedule; Female; Humans; Incidence; Kidney Transplantation; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Republic of Korea; Retrospective Studies; Risk Factors; Tertiary Care Centers; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

Methotrexate monotherapy is a common management strategy in rheumatoid arthritis (RA). Treatment with immunosuppression can lead to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). The treatment options for PJP include cotrimoxazole, clindamycin-primaquine and dapsone. Though these drugs are generally well tolerated, they can result in potentially severe adverse effects. Sometimes several undesired events may occur in a single patient, reminding us of Murphy's law. Herein, we report a case which exemplifies this adage. A 50-year-old female developed PJP, while on methotrexate therapy for RA and was treated with cotrimoxazole. The latter resulted in painful peripheral neuropathy, which improved after cotrimoxazole was stopped. Salvage therapy for PJP with primaquine-clindamycin, lead to another serious adverse event, methemoglobinemia. Withdrawing the offending drug resulted in dramatic improvement.

Topics: Anti-Bacterial Agents; Antimalarials; Clindamycin; Dapsone; Drug Therapy, Combination; Female; Humans; Law Enforcement; Methemoglobinemia; Middle Aged; New Zealand; Peripheral Nervous System Diseases; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination; Withholding Treatment

Topics: Aged; Androstadienes; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Fatal Outcome; Female; Humans; Immunocompromised Host; Lymphocyte Count; Lymphopenia; Piperazines; Pneumocystis; Pneumonia, Pneumocystis; Pyridines; Severity of Illness Index; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Agammaglobulinemia; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antirheumatic Agents; Churg-Strauss Syndrome; Delphi Technique; Duration of Therapy; Granulomatosis with Polyangiitis; Humans; Immunocompromised Host; Influenza Vaccines; Influenza, Human; Maintenance Chemotherapy; Microscopic Polyangiitis; Neutropenia; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Recurrence; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination; United Kingdom

Pneumocystis jirovecii, formerly known as Pneumocystis carinii, is an atypical fungal pathogen best known for causing Pneumocystis jirovecii pneumonia (PCP). The epidemiology of PCP is changing such that patients without HIV infection now comprise the largest subset of individuals diagnosed with PCP. While those with hematologic malignancies and organ transplants are at greatest risk for non-HIV-related PCP, this review will focus on PCP in patients with solid tumors. They are at risk for PCP due to their chemotherapy regimens and use of steroids in the management of various complications of treatment, and possibly because of the immunosuppressive effect of the cancer itself. In particular, patients with solid tumors being treated for metastatic spinal cord compression are at great risk for PCP. Patients with solid tumors and PCP face greater mortality than those with HIV infection. Multiple reviews have attempted to describe the ideal regimen of corticosteroids for metastatic spinal cord compression, but there is little consensus. We present 2 cases of patients with metastatic spinal cord compression due to prostate cancer undergoing radiation therapy and treatment with corticosteroids. These cases highlight the difficulties in predicting the length of corticosteroid therapy and the dangers that patients face without appropriate prophylaxis. This article will also provide a review of the current guidelines for PCP prophylaxis in patients undergoing treatment for metastatic spinal cord compression. We recommend empiric treatment with trimethoprim-sulfamethoxazole or dapsone in those patients with a sulfa allergy in all patients with solid tumors when any high-dose steroids are started for the treatment of metastatic spinal cord compression. Further research is needed to assess the epidemiology of PCP in patients with solid tumors and additional trials are necessary to refine PCP prophylaxis.

Topics: Adrenal Cortex Hormones; Aged; Anti-Bacterial Agents; Fatal Outcome; Humans; Male; Neoplasm Metastasis; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Prostatic Neoplasms; Spinal Cord Compression; Trimethoprim, Sulfamethoxazole Drug Combination

Due to the increasing use of immunosuppressant therapy, Pneumocystis jirovecii pneumonia (PJP) has become an emerging concern in human immunodeficiency virus (HIV)-negative patients. In this study, we conducted a retrospective study of 96 hospitalized patients with PJP from January 2015 to June 2019 at three tertiary comprehensive hospitals in Southern China. Information was collected regarding patient demographics, clinical manifestations, risk factors, laboratory analyses, radiological images, and treatment outcomes. PJP infection was most commonly found in middle-aged men. Kidney diseases (35.5%) and connective tissue diseases (38.7%) were the predominant risk factors for PJP. About half of the patients (48.4%) received glucocorticoid, immunosuppressant, and/or chemotherapy in a low dose or in a short-term (< 3 months). None of the patients had previously received trimethoprim-sulfamethoxazole (TMP-SMX) for PJP prophylaxis. All patients had two or more clinical manifestations (cough, dyspnea, fever, and chest pain). Biochemical investigations of CRP, ESR, PaO

Topics: Adult; Aged; Antifungal Agents; China; Female; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Tertiary Care Centers; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Humans; Methemoglobinemia; New Zealand; Peripheral Nervous System Diseases; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

We reported a Chinese boy with X-linked hyper IgM (XHIGM) syndrome, manifesting as recurrent and severe pneumonia caused by Pneumocystis jirovecii. His parents were healthy and unrelated. In August 2018, the 5-month-old boy manifested as cough and dyspnea, and then in July 2019, he was admitted because of the same symptoms. Immunological results of the two admissions both showed low IgG, low IgA, normal IgM and high levels of 1,3-β-D-glucan (BDG). Using next-generation sequencing (NGS), great reading counts of P. jirovecii were identified from the deep sputum in both admissions. Caspofungin combined with trimethoprim-sulfamethoxazole were used to anti-infection, and he recovered quickly. Whole-exome sequencing was performed for this family because of immune suppression, the disease-causing gene (exon 10-22 of CD40L) deletion for XHIGM syndrome was identified. NGS is beneficial for etiology diagnosis. Pneumocystis jirovecii pneumonia as an opportunistic infection could be recurrent in patients with XHIGM syndrome.

Topics: Caspofungin; Cough; Dyspnea; High-Throughput Nucleotide Sequencing; Humans; Hyper-IgM Immunodeficiency Syndrome, Type 1; Infant; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Background Co-trimoxazole is an antibiotic combination used for the treatment of Pneumocystis jirovecii pneumonia, amongst others. Co-trimoxazole is known to increase serum potassium. For this reason, Dutch guidelines advise serum potassium monitoring in high-risk patients. Objective This study aimed to determine average serum potassium rise after administration of intravenous co-trimoxazole in hospitalized patients, compared to intravenous ceftriaxone. This study also aimed to determine adherence to Dutch guidelines by measuring the incidence of serum potassium monitoring in these patients. Setting Five departments of the Canisius Wilhelmina Hospital, a teaching hospital in Nijmegen, the Netherlands. Method Data was collected and compared from patients that received intravenous co-trimoxazole (n = 66) and intravenous ceftriaxone (n = 132) in the period of November 2008-November 2017. For each patient using co-trimoxazole, two patients using ceftriaxone were included in a paired fashion. Baseline and follow-up potassium were collected, if available. Additionally, it was tested if serum potassium was measured around the initiation of antibiotic therapy. Main outcome measure Changes in serum potassium where obtainable in 30 patients using cotrimoxazole and 40 patients using ceftriaxone. When compared to ceftriaxone, administration of intravenous co-trimoxazole was associated with a significant mean increase in serum potassium (+ 0.55 mmol/l, 95% CI 0.29-0.80, p < 0.001). After correction for confounders (baseline potassium, estimated glomerular filtration rate 30 to < 60, the presence of haematological malignancies and the usage of corticosteroids), this effect shrunk noticeably, but remained significant (+ 0.28 mmol/l, 95% CI 0.03-0.53, p = 0.031). Results The incidence of hyperkalemia at follow-up was 20% in the cotrimoxazole group, compared to 5% in the ceftriaxone group. Despite this, serum potassium was often not measured in patients using intravenous cotrimoxazole, being 76% at baseline and 55% in the period of 48-120 h after antibiotic therapy initiation, compared to 87% and 34% in the ceftriaxone group respectively. Conclusion Adherence to Dutch guidelines was poor as serum potassium monitoring was often not performed. As intravenous co-trimoxazole usage is associated with a significant increase in mean serum potassium, monitoring is strongly recommended.

Topics: Anti-Bacterial Agents; Ceftriaxone; Drug Monitoring; Female; Glomerular Filtration Rate; Humans; Hyperkalemia; Male; Middle Aged; Netherlands; Pneumocystis carinii; Pneumonia, Pneumocystis; Potassium; Trimethoprim, Sulfamethoxazole Drug Combination

Lung transplantation (LT) is an identified risk factor for Pneumocystis pneumonia (PCP). However, PCP management and outcomes remain poorly described in LT recipients and PCP incidence is rarely documented in this population.. PCP episodes that occurred in 9 French LT centers between January 2010 and October 2017 were included in this analysis. PCP was defined as compatible clinical and radiologic findings associated with fungal identification.. Forty-seven PCP were included. The annual incidence rate of PCP was 2.7/1000 patients/year. Patients had a mean age of 53 ± 14 years. Median time from LT was 2.4 ± 3.0 years. Sixty-five percent of patients were not on prophylaxis at the time of PCP while all patients were receiving steroids at the time of PCP. Diagnosis was obtained by bronchoalveolar lavage in 91% (direct examination: 47%, PCR: 62%). The majority of patients were treated with trimethoprim-sulfamethoxazole (78%). Fifty-five percent of patients were hospitalized in ICU for organ failure (for which non-invasive ventilation was used for 21% and mechanical ventilation for 23%). Mortality rate was 15% at day 28 and reached 23% at day 90. Mortality was associated with decreased FEV1, everolimus treatment, Pseudomonas aeruginosa coinfection, fungal coinfection (especially Aspergillus sp.), mechanical ventilation and vasopressors. PCP primary prophylaxis, steroid modification during PCP and the number of immunosuppressive molecules were not associated with mortality.. PCP is associated with a high mortality in LT. Our data suggest the need for a lifetime PCP prophylaxis in LT recipients. The benefit of adjuvant steroids remains unclear.

Topics: Adult; Aged; Cohort Studies; Female; France; Humans; Lung Transplantation; Male; Middle Aged; Multicenter Studies as Topic; Pneumonia, Pneumocystis; Postoperative Complications; Retrospective Studies; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acidosis, Lactic; Aged; Dermatomyositis; Female; Humans; Pneumonia, Pneumocystis; Propylene Glycol; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Anti-HIV Agents; Asthma; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Diagnosis, Differential; DNA, Bacterial; Emtricitabine; Glucocorticoids; HIV Infections; Humans; Lung; Male; Middle Aged; Multiplex Polymerase Chain Reaction; Oxygen Inhalation Therapy; Pandemics; Pneumocystis carinii; Pneumonia, Pneumocystis; Pneumonia, Viral; Prednisolone; Raltegravir Potassium; Real-Time Polymerase Chain Reaction; RNA, Viral; SARS-CoV-2; Tenofovir; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

This study aimed to clarify the clinical characteristics of Pneumocystis jirovecii pneumonia (PJP) infection in patients with ulcerative colitis (UC) and to identify risk factors for PJP using a retrospective case-control study.. Of 4,525 patients with UC treated between 2007 and 2019, we identified those who satisfied the criteria for PJP. The Lichtiger clinical activity index (LCI) was compared between the initiation of immunosuppressive drug treatment and the onset of PJP. A retrospective case-control study was conducted using a PJP group and a non-PJP group.. Nine patients experienced PJP, of whom two died. Since October 2014, there were no cases of PJP among UC patients aged ≥50 years who were prescribed three or more immunosuppressive agents given prophylactic sulfamethoxazole-trimethoprim (TPM-SMX). The median LCI (range) was 13 (8-17) at the initiation of treatment versus 2 (1-8) at PJP onset (p = 0.016). The median time to PJP onset was 83 days after treatment initiation. In the PJP group the median age was significantly greater (p = 0.022), three immunosuppressants were used significantly more frequently (p = 0.004), and the lymphocyte counts during treatment were significantly lower (p < 0.01) than in the non-PJP group. The cut-off lymphocyte count that distinguished PJP patients from non-PJP patients was 570/μL according to a receiver-operating curve analysis.. Prophylactic administration of TPM-SMX prevented further cases of PJP. The onset of PJP occurred at the same time as the symptoms of UC were stabilizing and the immunosuppressive drugs were being reduced. Greater age, lower lymphocyte count, and treatment with three immunosuppressive drugs were risk factors for PJP.

Topics: Age Factors; Anti-Bacterial Agents; Case-Control Studies; Chemoprevention; Colitis, Ulcerative; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Japan; Lymphocyte Count; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; ROC Curve; Trimethoprim, Sulfamethoxazole Drug Combination

A Polymerase Chain Reaction-based diagnosis of

Topics: Adult; Hodgkin Disease; Humans; Incidence; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prospective Studies; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Urinary tract infection (UTI) is one of the most common infectious complications among renal transplant patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is routinely used as first-line prophylaxis against Pneumocystis pneumonia (PCP) and other opportunistic infections including UTI. Aerosolized pentamidine is an alternate agent used for PCP prophylaxis; however, it does not provide coverage against uropathogens. This is a retrospective study of 81 renal transplant recipients who received TMP-SMX or aerosolized pentamidine for PCP prophylaxis at our center over 1 year. Survival analysis demonstrated increased cumulative incidence of UTI among patients receiving pentamidine for PCP prophylaxis compared to those receiving TMP-SMX (log-rank test P < .001). Univariate and multivariate Cox proportional hazard regression model showed pentamidine prophylaxis (HR 3.740; 95% CI 1.745-8.016; P = .001) and female sex (HR 4.025; 95% CI 1.770-9.154; P = .001) to independently increase UTI risk. Age, induction agent, graft type, diabetes, and delayed graft function (DGF) were not associated with increased risk. This study concludes that the use of pentamidine for PCP prophylaxis compared to TMP-SMX is associated with increased risk of UTI. Secondary UTI prophylaxis may be considered for patients who are unable to tolerate TMP-SMX and who have other risk factors for UTI; however, the efficacy of this has not been studied.

Topics: Female; Humans; Kidney Transplantation; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection. Prophylaxis is recommended for patients with malignancies and trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line agent. Many paediatric patients receive second-line agents due to perceived adverse reactions from TMP-SMX.. The objective of the study is to determine the risk of PJP in patients receiving TMP-SMX vs. second-line medications for prophylaxis.. We conducted a retrospective, single centre, case-control study of paediatric oncology patients. Cases included children diagnosed with PJP by microscopy between 2000 and 2018 while being treated for a malignancy. Controls were matched by age, oncologic diagnosis, treatment protocol, phase of treatment and oncologic diagnosis date. For each case, up to 5 controls were randomly selected. The index date was the date of the PJP diagnosis for cases and the equivalent dummy date for controls.. Eleven cases with PJP were identified and matched with 50 controls. Six (55%) cases and 42 (84%) controls were on prophylaxis with TMP-SMX. The remaining patients received inhaled pentamidine (3 cases, 4 controls), dapsone (2 cases, 3 controls), or atovaquone (1 control). Myelosuppression was the most common reason to stop TMP-SMX. Cases with PJP were less likely to have been taking TMP-SMX in the 3 months before diagnosis when compared with controls (odds ratio: 0.15, 95% confidence interval: 0.01-0.97, p = 0.02).. TMP-SMX prophylaxis was associated with a lower risk of developing PJP compared with second-line treatments. Although alternate agents may be required in certain situations, efforts should be made to rechallenge with TMP-SMX when possible.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Case-Control Studies; Child; Child, Preschool; Female; Humans; Infant; Male; Neoplasms; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Combinations; Hodgkin Disease; Humans; Hypoglycemia; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Glucocorticoids; Humans; Opportunistic Infections; Pneumonia, Pneumocystis; Rheumatic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) is a bactericidalantibiotic. The most common adverse effect of TMP/SMX is skinrashes and gastrointestinal symptoms. Although hyperkalemia canoccur with TMP/SMX component but hyponatremia is uncommon. A55- year old woman, known case of rheumatoid arthritis, presentedwith fever and mild dyspnea. According to diagnostic work upthe infection with pneumocystis jirovecii was confirmed. TMP/SMX was started but after 10 days the patient acutely representedwith nausea and became lethargic. The laboratory studies showedmoderate hyperkalemia and severe hyponatremia. TMP/SMX wasstopped and alternative treatment started. Upon discontinuation ofthe drug, serum sodium and potassium levels were both changed tonormal. Hyponatremia as a life threatening adverse effect appearsto be rare with TMP-SMX therapy, but clinicians should be awareof electrolyte disturbances developed with this drug and electrolytemonitoring should always be considered.

Topics: Female; Humans; Hyperkalemia; Hyponatremia; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this study was to investigate the efficacy of combination therapy of caspofungin and TMP/SMZ (trimethoprim/sulfamethoxazole) in moderate to severe pneumocystis jirovecii pneumonia (PJP) in patients without human immunodeficiency virus infection (HIV) and the relationship between therapeutic effect and plasma (1, 3) Beta-d-Glucan (BDG) levels.. We retrospectively reviewed HIV-negative patients with PJP diagnosed in our department, who were treated with combination therapy of caspofungin and TMP/SMZ or monotherapy of TMP/SMZ during a six and a half year period.. A total of 126 moderate to severe PJP patients were enrolled in the study. In the multivariate analysis, low lymphocyte counts, high serum lactate dehydrogenase levels at the diagnosis of PJP and progression to shock were significant risk factors for death. In all patients, there was no significant difference in risk of death at 3 months. In the group of BDG≥800pg/m, patients receiving combination therapy was associated with a significantly decreased risk of death at 3 months, whereas in the group of BDG<800pg/ml, there were no statistically significant difference in survival rate between the two treatment regimens.. High initial plasma (1, 3) Beta-d-Glucan concentration may be a predictor of satisfactory caspofungin response to HIV-negative patients with PJP. Based on our findings, we suggest the choice of combination therapy with caspofungin and TMP/SMZ as the initial treatment when BDG≥800pg/ml in moderate to severe HIV-negative patients with PJP.

Topics: Adult; Antifungal Agents; beta-Glucans; Caspofungin; Drug Monitoring; Female; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Bacterial Agents; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiation Pneumonitis; Steroids; Thoracic Neoplasms; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the incidence of pneumocystis pneumonia (PCP) and its risk factors in patients with rheumatic disease receiving non-high-dose steroid treatment, along with the risks and benefits of PCP prophylaxis.. This study included 28,292 treatment episodes with prolonged (≥ 4 weeks), non-high-dose steroids (low dose [< 15 mg/day, n = 27,227] and medium dose [≥ 15 to < 30 mg/day, n = 1065], based on prednisone) over a 14-year period. Risk factors for PCP and prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) were investigated if the 1-year incidence rate (IR) of PCP in each dose group was > 0.1/100 person-years. Cox regression with LASSO was used for analysis.. One-year PCP IR in the low-dose group was 0.01 (95% CI 0.001-0.03)/100 person-years, and only the medium-dose group showed eligible PCP IR for further analysis. In the medium-dose group, prophylactic TMP-SMX was administered in 45 treatment episodes while other episodes involved no prophylaxis (prophylaxis group vs. control group). In 1018.0 person-years, 5 PCP cases occurred exclusively in the control group, yielding an IR of 0.5 (0.2-1.2)/100 person-years. Concomitant steroid-pulse treatment and baseline lymphopenia were the most significant risk factors for PCP. Treatment episodes with at least one of these factors (n = 173, high-risk subgroup) showed higher 1-year PCP IR (3.4 (1.1-8.0)/100 person-years), while no PCP occurred in other treatment episodes. TMP-SMX numerically reduced the risk (adjusted HR = 0.2 (0.001-2.3)) in the high-risk subgroup. The IR of adverse drug reactions (ADRs) related to TMP-SMX was 41.5 (22.3-71.6)/100 person-years, including one serious ADR. The number needed to treat with TMP-SMX to prevent one PCP in the high-risk subgroup (31 (17-226)) was lower than the number needed to harm by serious ADR (45 (15-∞)).. Incidence of PCP in patients with rheumatic diseases receiving prolonged, medium-dose steroids depends on the presence of risk factors. Prophylactic TMP-SMX may have greater benefit than potential risk in the high-risk subgroup.

Topics: Adult; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Glucocorticoids; Humans; Incidence; Male; Middle Aged; Pneumonia, Pneumocystis; Prognosis; Republic of Korea; Retrospective Studies; Rheumatic Diseases; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

The prevalence of pneumocystis pneumonia (PCP) and associated hypoxic respiratory failure is increasing in human immunodeficiency virus (HIV)-negative patients. However, no prior studies have evaluated the effect of early anti-PCP treatment on clinical outcomes in HIV-negative patient with severe PCP. Therefore, this study investigated the association between the time to anti-PCP treatment and the clinical outcomes in HIV-negative patients with PCP who presented with hypoxemic respiratory failure.. A retrospective observational study was performed involving 51 HIV-negative patients with PCP who presented in respiratory failure and were admitted to the intensive care unit between October 2005 and July 2018. A logistic regression model was used to adjust for potential confounding factors in the association between the time to anti-PCP treatment and in-hospital mortality.. All patients were treated with appropriate anti-PCP treatment, primarily involving trimethoprim/sulfamethoxazole. The median time to anti-PCP treatment was 58.0 (28.0-97.8) hours. Thirty-one (60.8%) patients were treated empirically prior to confirmation of the microbiological diagnosis. However, the hospital mortality rates were not associated with increasing quartiles of time until anti-PCP treatment (P = 0.818, test for trend). In addition, hospital mortality of patients received early empiric treatment was not better than those of patients received definitive treatment after microbiologic diagnosis (48.4% vs. 40.0%, P = 0.765). In a multiple logistic regression model, the time to anti-PCP treatment was not associated with increased mortality. However, age (adjusted OR 1.07, 95% CI 1.01-1.14) and failure to initial treatment (adjusted OR 13.03, 95% CI 2.34-72.65) were independently associated with increased mortality.. There was no association between the time to anti-PCP treatment and treatment outcomes in HIV-negative patients with PCP who presented in hypoxemic respiratory failure.

Topics: Adult; Age Factors; Aged; Anti-Bacterial Agents; Critical Care; Female; HIV Seronegativity; Hospital Mortality; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Respiratory Insufficiency; Retrospective Studies; Time-to-Treatment; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line agent for Pneumocystis jiroveci pneumonia (PJP) prophylaxis for solid organ transplant (SOT) recipients because of its efficacy for this indication, extended antimicrobial coverage, and favorable cost. Reported sulfonamide allergy is not uncommon and often results in TMP-SMX avoidance. Desensitization offers an efficacious and cost-effective alternative to TMP-SMX avoidance. Herein, we reviewed our experience with desensitization during the index transplant hospitalization among 52 SOT recipients with history of a non-anaphylactic sulfonamide allergy. Of those enrolled in the desensitization protocol, 92% (48/52) completed the protocol, with nearly 80% (41/52) still on TMP-SMX at 3 months without adverse reaction. Eleven patients discontinued TMP-SMX (7 for allergic reactions and 4 for non-allergic reasons) and switched to pentamidine. A cost savings of $575 per desensitization was calculated based on annual wholesale drug prices, for a total savings of $23 575. Additionally, the protocol did not delay discharge in any patient nor was it associated with any severe allergic reactions. These findings suggest TMP-SMX desensitization is safe and effective in SOT recipients with a history of non-anaphylactic, non-life-threatening sulfonamide hypersensitivity.

Topics: Cost Savings; Desensitization, Immunologic; Drug Hypersensitivity; Feasibility Studies; Female; Humans; Male; Middle Aged; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Severity of Illness Index; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is a life-threatening fungal infection occurring in immunocompromised patients such as HIV-positive patients with low CD4 cell count or patients under heavy immunosuppressive therapy. We report the case of a 59-year-old male with severe diffuse cutaneous systemic sclerosis presenting with asthenia, dry cough and worsening shortness of breath for the last 15 days. Biological studies were remarkable for PTH-independent severe hypercalcemia with low 25-hydroxyvitamin D and a paradoxically elevated 1,25-dihydroxyvitamin D. Early bronchoalveolar lavage allowed for PCP diagnosis and targeted treatment. We discuss the underlying physiopathology and difficulties regarding prophylaxis and treatment.

Topics: Humans; Hypercalcemia; Immunocompromised Host; Immunotherapy; Male; Middle Aged; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Scleroderma, Diffuse; Trimethoprim, Sulfamethoxazole Drug Combination

BACKGROUND Trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as prophylaxis against Pneumocystis pneumonia (PCP) in renal transplant recipients. The optimal duration of prophylaxis is unknown. Longer duration of prophylaxis may increase the risk of adverse effects. The aim of this retrospective observational cohort study was to assess the impact of increasing duration of TMP-SMX prophylaxis from 3 to 6 months after transplant on drug-resistant urinary tract infection (UTI), hyperkalemia, peripheral blood cytopenias, and incidence of PCP. MATERIAL AND METHODS Patients transplanted over a 4.5-year period before and after a change in protocol from 3- to 6-months TMP-SMX prophylaxis in our unit were grouped according to planned duration of prophylaxis, and results were analyzed on an intention-to-treat basis. Baseline characteristics, laboratory values, and all urine microbiology results in the 6 months after transplant were analyzed. RESULTS The overall UTI incidence rate was higher in the 3-month (3-m) treatment group than the 6-month (6-m) treatment group (0.52 vs. 0.33 UTI per 100 patient days; rate ratio 1.56 [95% CI 1.27-1.95]). However, this was not attributable to TMP-SMX: the incidences were significantly different in months 0-3 but not months 4-6. Twenty-eight multi-resistant UTIs occurred in the 3-m group, but there were none in the 6-m group (p=0.004). There were no significant differences in renal function, serum potassium, or cytopenias during the first 6 months. There were 15 cases of PCP in the 3-m group, 3 cases in the 6-m group, and no cases during prophylaxis. CONCLUSIONS Extending the duration of TMP-SMX prophylaxis was not associated with change in frequency of UTIs or multi-drug-resistant UTIs, nor was it associated with increased adverse events. TMP-SMX is an effective PCP prophylaxis, and these data support recommendations to extend the duration of prophylaxis after transplant.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cohort Studies; Drug Administration Schedule; Female; Hematologic Diseases; Humans; Hyperkalemia; Kidney Transplantation; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Glucocorticoids; Humans; Pneumonia, Pneumocystis; Rheumatic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Glucocorticoids; Humans; Pneumonia, Pneumocystis; Rheumatic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole is associated with the development of hyponatremia, hyperkalemia and elevated serum creatinine, especially when combined with inhibitors of the renin-angiotensin-aldosterone system (RAAS).. We evaluated whether high-grade glioma patients taking renin-angiotensin-aldosterone system inhibitors receiving low-dose cotrimoxazole for. We conducted a retrospective chart review of adult neuro-oncology patients treated for WHO Grade III or IV glioma between 2013 and 2016. Patient serum Na, K, creatinine, and eGFR were compared (renin-angiotensin-aldosterone system vs. non-renin-angiotensin-aldosterone system) using the chi-square test. Binary logistic regression analysis was then performed to account for differences between cohorts.. Of 63 patients (35 non-renin-angiotensin-aldosterone system, 28 renin-angiotensin-aldosterone system), patients in the renin-angiotensin-aldosterone system cohort were more likely to experience a laboratory disturbance (odds ratio=3.17,. Adding low-dose cotrimoxazole for

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Antibiotic Prophylaxis; Creatinine; Drug Interactions; Female; Glioma; Glomerular Filtration Rate; Humans; Hyperkalemia; Male; Middle Aged; Neoplasm Grading; Pneumonia, Pneumocystis; Potassium; Renin-Angiotensin System; Retrospective Studies; Sodium; Trimethoprim, Sulfamethoxazole Drug Combination

Both co-trimoxazole and pentamidine are used for the treatment of pneumocystis pneumonia (PCP) and are known to cause hypoglycemia as an adverse drug reaction. Here, we describe a rare case of a late-diagnosed female patient with acquired immunodeficiency syndrome (AIDS) who developed the first hypoglycemic attack as an adverse effect of co-trimoxazole, followed by a second hypoglycemic attack as an adverse effect of pentamidine. Physicians caring for patients with AIDS and PCP should be aware of possible hypoglycemia in patients with many risk factors.

Topics: Acquired Immunodeficiency Syndrome; Aged; Anti-Infective Agents; Atovaquone; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hypoglycemia; Pentamidine; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We present the case of a human immunodeficiency virus (HIV)-infected patient who arrived at our emergency department with fever, headache and exertional dyspnea. Throughout their stay, a chest x-ray was taken and a rounded opacity in his left lung was observed. CT images showed same abnormality and also ground glass opacities were seen. Symptoms and images strongly suggested a pulmonary infection due to pneumocystis jirovecii, however a presence of a round lesion should always lead to neoplasia being suspected. We empirically started treatment based on trimethoprim and sulfamethoxazole. Once available, flexible bronchoscopy and bronchoalveolar lavage was performed and stained preparations from his respiratory specimens confirmed the diagnosis of pulmonary pneumocystis infection. Finally, after 4 days of antibiotic therapy, an important clinical improvement was documented; a new chest x-ray was performed and the previous rounded opacity was absent. This finding strongly suggested a case of round pneumonia.

Topics: Adult; Antifungal Agents; Diagnosis, Differential; Emergency Service, Hospital; HIV Infections; Humans; Lung; Lung Neoplasms; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography, Thoracic; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

A mortality rate of non-human immunodeficiency virus-infected pneumocystis pneumonia (non-HIV PCP) is 30-60%. But the effectiveness of adjunctive corticosteroids with trimethoprim-sulfamethoxazole has been unclear, and we examined whether it lowered risk of mortality in non-HIV PCP.. We did an observational study of adult non-HIV PCP patients from April 2010 through March 2016, using Japanese nationwide healthcare records of the Diagnostic Procedure Combination database (DPC). The risk was estimated by the time-dependent Cox regression analyses with inverse probability weights.. 1299 eligible non-HIV PCP patients were identified. 737 patients were severe respiratory status (partial pressure of oxygen in arterial blood [PaO. The adjunctive corticosteroids were associated with lower risk of 60-day mortality in severe non-HIV PCP patients.

Topics: Adrenal Cortex Hormones; Adult; Aged; Female; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the effectiveness and safety of lower-dose sulfamethoxazole/trimethoprim therapy (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) in patients with systemic rheumatic diseases.. In this multicenter retrospective study, we compared effectiveness and safety of SMX/TMP for the treatment of PCP among patients divided into three groups according to the initial dosage of SMX/TMP: the low, ≤10 mg/kg/day; the intermediate, 10-15 mg/kg/day; and the high and conventional, 15-20 mg/kg/day for TMP dose.. Eighty-one patients, including 22, 30, and 29 patients in the low-, the intermediate- and the high-dose group could be analyzed and the 30-day survival rate were 100%, 93.3%, and 96.7%, respectively (P = 0.28). There were significant dose-dependent increasing trends of severe adverse drug reactions (ADRs) for SMX/TMP that were graded as ≥3 according to the Common Terminology Criteria for Adverse Events. When stratified by presence of severe hypoxemia defined by alveolar-arterial O2 gradient ≥45 mmHg, the 30-day survival and treatment modification rate were similar among the three groups, but frequency of severe ADRs were significantly decreased in the low-dose group. The low-dose group was independently and negatively associated with treatment modification within 14 days and severe ADRs.. Lower dose SMX/TMP therapy with ≤10 mg/kg/day for TMP was as effective as higher dose therapy for the treatment of PCP and associated with lower rates of treatment modification and severe ADRs in patients with systemic rheumatic diseases.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Female; Humans; Immunosuppression Therapy; Male; Middle Aged; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Rheumatic Diseases; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is a common opportunistic infection caused by Pneumocystis jirovecii. Its incidence at 2 years or more after liver transplant (LT) is < 0.1%. PCP-related spontaneous pneumothorax and/or pneumomediastinum is rare in patients without the human immunodeficiency virus, with an incidence of 0.4-4%.. A 65-year-old woman who had split-graft deceased-donor LT for primary biliary cirrhosis developed fever, dyspnea and dry coughing at 25 months after transplant. Her immunosuppressants included tacrolimus, mycophenolate mofetil, and prednisolone. PCP infection was confirmed by molecular detection of Pneumocystis jirovecii,in bronchoalveolar lavage. On day-10 trimethoprim-sulphamethoxazole, her chest X-ray showed subcutaneous emphysema bilaterally, right pneumothorax and pneumomediastinum. Computed tomography of the thorax confirmed the presence of right pneumothorax, pneumomediastinum and subcutaneous emphysema. She was managed with 7-day right-sided chest drain and a 21-day course of trimethoprim-sulphamethoxazole before discharge.. Longer period of PCP prophylaxis should be considered in patients who have a higher risk compared to general LT patients. High index of clinical suspicion, prompt diagnosis and treatment with ongoing patient reassessment to detect and exclude rare, potentially fatal but treatable complications are essential, especially when clinical deterioration has developed.

Topics: Aged; Antibiotic Prophylaxis; Female; Humans; Immunosuppressive Agents; Liver Transplantation; Mediastinal Emphysema; Pneumocystis carinii; Pneumonia, Pneumocystis; Pneumothorax; Subcutaneous Emphysema; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; CD4 Lymphocyte Count; Diagnosis, Differential; Dyspnea; HIV Infections; Humans; Lung; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients on steroid therapy for connective tissue diseases. The standard agent for primary PCP prophylaxis is trimethoprim/sulfamethoxazole (TMP-SMX), although this agent can cause common adverse reactions, including myelosuppression and renal toxicity, that result in cessation. Aerosolized pentamidine and oral atovaquone are alternatives for PCP prophylaxis. The efficacies of atovaquone, pentamidine, and TMP-SMX to prevent PCP in patients with connective tissue diseases have never been compared.. Hospitalized patients with connective tissue diseases who started steroid therapy and PCP prophylaxis were enrolled. PCP prophylaxis regimens were oral TMP-SMX, aerosolized pentamidine, or oral atovaquone. Information was retrospectively collected from medical records about laboratory findings, duration of PCP prophylaxis, and reasons for terminating PCP prophylaxis.. Ninety-six patients received PCP prophylaxis. All of them were initially treated with TMP-SMX, but this was replaced during the study period with pentamidine in 33 patients and with atovaquone in 7. Forty-one (43%) patients discontinued TMP-SMX because of adverse events, and 5 (15%) also discontinued pentamidine. None of the patients discontinued atovaquone. The most frequent causes of TMP-SMX and pentamidine cessation were cytopenia (N = 15) and asthma (N = 2). The rates of continuing treatment with TMP-SMX, pentamidine, and atovaquone at one year after starting PCP prophylaxis were 55.3%, 68.6%, and 100%, respectively (P = 0.01). None of the patients developed PCP.. Although TMP-SMX for PCP prophylaxis had to be discontinued in 43% of patients with connective tissue diseases, pentamidine and atovaquone were well tolerated.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antibiotic Prophylaxis; Asthma; Atovaquone; Connective Tissue Diseases; Drug Therapy, Combination; Female; Hematologic Diseases; Humans; Male; Middle Aged; Opportunistic Infections; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pneumocystis jirovecii causes severe pneumonia in immunocompromised hosts. Human immunodeficiency virus infection, malignancy, solid organ or hematopoietic cell transplantation, and primary immune deficiency compose the risk factors for Pneumocystis pneumonia (PCP) in children, and PCP can be an initial clinical manifestation of primary immune deficiency.. A 5-month-old infant presented with cyanosis and tachypnea. He had no previous medical or birth history suggesting primary immune deficiency. He was diagnosed with interstitial pneumonia on admission.. He was diagnosed with PCP, and further evaluations revealed underlying X-linked hyper-IgM syndrome.. He was treated with trimethoprim/sulfamethoxazole for PCP, and eventually received allogeneic hematopoietic cell transplantation for hyper-IgM syndrome.. Twenty months have passed after transplantation without severe complications.. PCP should be considered in infants presenting with severe interstitial pneumonia even in the absence of evidence of immune deficiency. Primary immune deficiency should also be suspected in infants diagnosed with PCP.

Topics: Anti-Bacterial Agents; Hematopoietic Stem Cell Transplantation; Humans; Hyper-IgM Immunodeficiency Syndrome, Type 1; Infant; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aftercare; Antimalarials; Antiprotozoal Agents; Atovaquone; Brain; Brain Edema; Female; Humans; Kidney Calculi; Liver Transplantation; Magnetic Resonance Imaging; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Sulfadiazine; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Ultrasonography

Detecting Pneumocystis jirovecii by bronchoalveolar lavage or lung biopsy is the gold standard for diagnosis of P. jirovecii pneumonia (PJP); however, these techniques are not always applicable in children because of their high invasiveness. We report two pediatric cases of PJP diagnosed by polymerase chain reaction (PCR) of gastric lavage that were successfully treated. To date, there are no reported cases of using PCR of gastric lavage to diagnose PJP. On the day of PJP onset, both the infants required respiratory support and infiltrative shadows were observed in both lung fields on chest radiography. Furthermore, their (1 → 3)-β-D glucan levels were elevated. P. jirovecii was detected by PCR of gastric lavage and trimethoprim-sulfamethoxazole was administered for 3 weeks, following which their condition improved. They were long-term steroid users, but without any prophylaxis. PCR of gastric lavage in cases of suspected PJP may help in confirming the diagnosis in children who have mild to moderate airway symptoms, or have difficulty with invasive examination like bronchoscopy.

Topics: DNA, Bacterial; Gastric Lavage; Humans; Immunocompromised Host; Infant; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Hyperkalaemia is a potentially life-threatening condition frequently encountered in hospitalised patients. Among the many causes of hyperkalaemia, drugs have often been implicated. In the South African context, with the high burden of HIV, there is an increased incidence of opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP), and consequently many patients receive high doses of trimethoprim-sulfamethoxazole. A lesser-known side-effect of the trimethoprim component of this combination antibiotic is hyperkalaemia. We report a case in which life-threatening hyperkalaemia developed after institution of high-dose co-trimoxazole for PJP.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Female; HIV Infections; Humans; Hyperkalemia; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Fibrosing interstitial lung disease is the poor prognostic non-infectious lung disease by unknown etiology. Here, we present one case developing interstitial pneumonia with fibrosis after treatment of pneumocystis pneumonia (PCP) in newly diagnosed HIV-1 infected case.. A previously healthy 63-year old male was referred to our institute because of protracted dyspnea on effort in 2 weeks after pneumocystis pneumonia treatment. At referral, arterial blood oxygen pressure was within normal range (93.5 mmHg) at rest, but decreased rapidly 30 s after a slow walk (44.5 mmHg). Respiratory function tests showed severe restrictive ventilator impairment (vital capacity = 36.5%; forced expiratory volume in 1 s = 107.4%). Chest computed tomography showed severe fibrotic changes at bilateral basal parts and diffuse fibrotic changes in which PCP lesions were seen initially in previous images although β-D glucan was not elevated and P. jirovecii was not detected in saliva at referral. Other etiologies of fibrotic IP including infectious and/or autoimmune diseases were excluded by serology. Fibrotic lesion did not expand thereafter although it had not responded to the high-dose corticosteroid therapy.. We report the first case of fibrosing interstitial lung disease triggered by HIV-related PCP.

Topics: AIDS-Related Opportunistic Infections; beta-Glucans; Forced Expiratory Volume; HIV Infections; Humans; Immunocompromised Host; Lung; Lung Diseases, Interstitial; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for anti-Pneumocystis jirovecii pneumonia (PcP) prophylaxis in kidney transplant recipients (KTR). Post-transplant management balances preventing PcP with managing TMP-SMX-related adverse effects. TMP-SMX dose reduction addresses adverse effects but its implications to incident PcP are unclear.. We performed a retrospective review of all patients transplanted between 2011 and 2015 prescribed daily single strength TMP-SMX for twelve months post-transplantation as PcP prophylaxis. Actual TMP-SMX dose and duration, adverse effects, number of dose reductions and reasons, and PcP events were captured. Multivariate logistic regression analyses for risk factors associated with dose reduction were performed.. Of 438 KTR, 233 (53%) maintained daily TMP-SMX and 205 (47%) sustained ≥1 dose reduction, with the point prevalence of a reduced dose regimen being between 18 and 25%. Median duration for daily TMP-SMX was 8.45/12 months, contributing 4137 patient-months daily TMP-SMX and 1110 patient-months with a reduced dose. PcP did not occur in any patients. There were 84 documented dose reductions for hyperkalemia and 102 for leukopenia, with 12 and 7 patients requiring TMP-SMX cessation. In multivariate analysis, a living donor transplant protected against hyperkalemia (Odds Ratio 0.46, 95% CI 0.26-0.83, p < 0.01) while acute rejection risked leukopenia (Odds Ratio 3.31, 95% CI 1.39-7.90, p = 0.006).. TMP-SMX dose reduction is frequent in the first post-transplant year but PcP does not occur. To limit the need for TMP-SMX dose reduction due to adverse effects, a clinical trial comparing daily to thrice weekly single strength TMP-SMX in de-novo KTR is justified.

Topics: Adult; Aged; Aged, 80 and over; Antibiotic Prophylaxis; Female; Humans; Kidney Transplantation; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Transplant Recipients; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia in non-HIV patients is infrequent and characterized by atypical presentations and increased severity. Although hematogenous dissemination from the lungs can lead to extrapulmonary infections, isolation of oocysts from blood in human subjects has not been documented. We report a case of P. jiroveci pneumonia with persistent isolation of oocysts from blood and positivity of P. jiroveci polymerase chain reaction. The patient presented with bilateral diffuse pulmonary nodules and received prolonged treatment with trimethoprim/sulfamethoxazole.

Topics: Antifungal Agents; Blood; Fungemia; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Trimethoprim, Sulfamethoxazole Drug Combination

Although Pneumocystis pneumonia (PCP), a life-threatening infection, has been reported in patients with non-Hodgkin B-cell lymphoma (BNHL) who were treated with rituximab-containing chemotherapies (R-CTX), the PCP prophylaxis regimen awaits establishment to date. This study reports a retrospective analysis of the efficacy and safety of a low-dose trimethoprim/sulfamethoxazole (TMP/SMX) in patients with BNHL receiving R-CTX. We retrospectively analyzed 156 patients newly diagnosed with BNHL who received R-CTX at our institute from 2010 to 2015. We collected patients' clinical and laboratory data, including lymphocytes count, IgG level, PCP prophylaxis regimens, and adverse events (AEs). Patients were categorized into the following two groups based on the TMP/SMX regimen: group A (33 patients; 80 mg/400 mg×3/week) or group B (65 patients; 160 mg/800 mg×2/week). Both lymphocytes count and IgG level declined during R-CTX. No patient developed PCP. Patients in group B exhibited a significantly higher incidence of AEs (18.2% vs. 63.1%; p<0.05) and increased AST (6.1% vs. 26.6%; p<0.05), compared with those in group A. Thus, TMP/SMX (80 mg/400 mg×3/week) effectively prevents PCP and is preferable because of the lower rates of AEs.

Topics: Humans; Lymphoma, Non-Hodgkin; Pneumonia, Pneumocystis; Retrospective Studies; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination

Systemic lupus erythematosus (SLE) complicated with Pneumocystis jiroveci pneumonia (PCP) is a clinical complex with unsatisfying treatment efficacy and poor prognosis which is difficult to be diagnosed at early stage. The present study aimed to investigate the clinical features of SLE with PCP, recognize the early onset indicating factors, and evaluate the treatment efficacy of combined caspofungin and trimethoprim/sulfamethoxazole (coSMZ).We reviewed data of 9 patients admitted with SLE-PCP and treated with caspofungin combined with coSMZ at Tangshan Gongren Hospital from January 2013 to December 2017. Patients' clinical manifestation and laboratory data [leucocyte, lymphocyte, cluster of differentiation 4 (CD4)T cell, lactate dehydrogenase (LDH), blood gas, etc] were compared before and after treatments. And the early onset factors of SLE-PCP, treatment efficacy of combined caspofungin and CoSMZ were analyzed.Among these 9 patients, 8 patients suffered renal impairment, and all of them had been taking prednisone in the past 3 months at an average dose of 29.4 ± 13.6 mg/day. In addition, they had taken at least one kind of immunosuppressants. Laboratory data (leucocyte, lymphocyte, CD4T cell, PaO2, LDH) were remarkably abnormal at hospital admission, but they were improved significantly after 2 weeks of treatment, which is also statistically significant (P < .05), except that leukocyte had no significance change to the value at admission (P = .973). In addition, none of the studied patients died.The results of the study indicated that long-term use of glucocorticoids and immunosuppressants, low CD4T cell count, and renal impairment are the early-onset factors for SLE-PCP, caspofungin, when combined with CoSMZ, it could be a promising and effective strategy to treat SLE with PCP.

Topics: Adult; Anti-Infective Agents; Caspofungin; Drug Therapy, Combination; Female; Humans; Lupus Erythematosus, Systemic; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

For patients with non-human immunodeficiency virus (HIV) Pneumocystis pneumonia (PCP), data are limited on serial changes in serum biomarkers and the correlations with clinical outcomes.. This study evaluated serial change in serum biomarkers and clinical outcomes of non-HIV PCP.. We retrospectively reviewed data from 63 patients treated for non-HIV PCP at Toho University Omori Medical Center. The patients were classified as survivors and nonsurvivors on the basis of 60-day PCP mortality. The groups were compared for clinical course and levels of serum biomarkers (β-D glucan, Krebs von den Lungen-6 antigen [KL-6], and surfactant protein-D [SP-D]), which were measured at baseline, and 7 days and 14 days after starting treatment. In addition, serial changes in serum biomarkers were analyzed in survivors and nonsurvivors.. There were 14 PCP nonsurvivors and 49 survivors. Biomarker values were not different between groups at baseline. At 7 and 14 days after starting treatment, the proportions of patients with elevated β-D glucan and KL-6 did not significantly differ between groups; however, the proportion of patients with elevated SP-D was significantly lower among survivors than among nonsurvivors (57.1% vs. 100%, p = 0.009; 30% vs. 100%, p < 0.001; respectively). SP-D on day 14 was significantly lower than that at baseline among survivors (99.6 [61.0-190.3] vs. 156 [100.8-283.5]; p = 0.045) but significantly higher among nonsurvivors (974 [744.5-1565] vs. 317 [211-448]; p = 0.03).. Serum SP-D value continues to increase after failure of treatment for non-HIV PCP and may thus be associated with outcomes for non-HIV PCP patients.

Topics: Aged; Anti-Bacterial Agents; beta-Glucans; Biomarkers; Combined Modality Therapy; Female; Glucocorticoids; Humans; Immunocompromised Host; Male; Middle Aged; Mucin-1; Oxygen Inhalation Therapy; Pneumocystis carinii; Pneumonia, Pneumocystis; Pulmonary Surfactant-Associated Protein D; Retrospective Studies; Survivors; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

The clinical characteristics of Pneumocystis jirovecii pneumonia (PCP) in patients with immunodeficiency virus (HIV) infection (HIV-PCP) differ from those in patients without HIV infection (non-HIV-PCP). We analyzed 31 adult HIV-PCP cases and 44 non-HIV-PCP cases between 2008 and 2018. The symptomatic period before the diagnosis was shorter in non-HIV-PCP (5 [3-8] days vs. 29 [14-55] days, P < 0.001) and the overall survival rate was lower in the non-HIV-PCP group (P = 0.022). Serum β-D glucan positivity (72.7% vs. 93.5%, P = 0.034) and Grocott stain positivity for Pneumocystis jirovecii in the bronchoalveolar lavage fluid (4.3% vs. 73.3%, P < 0.001) were significantly lower in the non-HIV-PCP group. This difficulty in laboratory diagnosis possibly resulted in the administration of concurrent antibiotics such as quinolones and macrolides (56.8% vs. 19.4% P = 0.002) in the non-HIV-PCP group. The adverse effects due to trimethoprim-sulfamethoxazole were more frequently observed in HIV-PCP (86.2% vs. 35.3%, P < 0.001). The duration of discontinuation of trimethoprim-sulfamethoxazole was 11 [8-14.5] days in HIV-PCP cases. Co-administration of adjunctive corticosteroid therapy did not mitigate hypersensitivity to trimethoprim-sulfamethoxazole. Our analysis indicated that the characteristics of PCP in patients with or without HIV was quite different. HIV-positive patients with PCP should be monitored closely to avoid adverse effects due to trimethoprim-sulfamethoxazole. Because positivity polymerase chain reaction test for P. jirovecii remained high (91.7%), it is suggested that bronchofiberscopy is warranted for diagnosis of PCP in HIV-negative patients.

Topics: Adult; Aged; Anti-Bacterial Agents; Female; HIV Infections; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Allografts; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Nocardia; Nocardia Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The efficacy of low-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be acceptable for the treatment of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected patients, with a low incidence of adverse reactions. This study is aimed to evaluate the efficacy and safety of such a regimen for the treatment of non-HIV PCP.. We retrospectively enrolled 24 consecutive patients diagnosed with non-HIV PCP who were treated with low-dose TMP-SMX (TMP, 4-10 mg/kg/day; SMX, 20-50 mg/kg/day). Data of the conventional-dose treatment were used as reference. The primary endpoints were the 30- and 180-day survival rates from the day of treatment, and secondary endpoints were the incidence of each adverse reaction and dropout rate from the initial TMP-SMX regimen. The survival rate was estimated using the Kaplan-Meier method with 95% confidence interval (CI).. The median age of patients was 72 years (54.2% men), and connective tissue disease was the most frequent underlying disease (66.7%) in the low-dose group. The 30- and 180-day survival rates were 95.8% (95% CI: 88.2-100.0%) and 91.0% (95% CI: 79.9%-100.0%), respectively, in the low-dose group and 69.0% (95% CI: 54.0%-88.0%) and 51.5% (95% CI: 36.1%-73.4%), respectively, in the conventional-dose group. The total adverse reaction rate was 58.3% in the low-dose group and 72.4% in the conventional-dose group. A total of 75.0% of patients in the low-dose group and 31.0% in the conventional-dose group completed treatment with the initial regimen.. Low-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Dosage Calculations; Female; Humans; Immunocompromised Host; Japan; Male; Pneumonia, Pneumocystis; Retrospective Studies; Safety; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

While trimethoprim-sulfamethoxazole is considered first-line therapy for Pneumocystis pneumonia prevention in renal transplant recipients, reported adverse drug reactions may limit use and increase reliance on costly and less effective alternatives, often aerosolized pentamidine. We report our experience implementing a protocolized approach to trimethoprim-sulfamethoxazole adverse drug reaction assessment and rechallenge to optimize prophylaxis in this patient cohort. We retrospectively reviewed 119 patients receiving Pneumocystis pneumonia prophylaxis prior to and after protocol implementation. Forty-two patients (35%) had 48 trimethoprim-sulfamethoxazole adverse drug reactions documented either at baseline or during the prophylaxis period, of which 83% were non-immune-mediated and 17% were immune-mediated. Significantly more patients underwent trimethoprim-sulfamethoxazole rechallenge after protocol implementation (4/22 vs 23/27; P = .0001), with no recurrence of adverse drug reactions in 74%. In those who experienced a new or recurrent reaction (26%), all were mild and self-limiting with only 1 recurrence of an immune-mediated reaction. After protocol implementation, aerosolized pentamidine-associated costs were reduced. The introduction of a standard approach to trimethoprim-sulfamethoxazole rechallenge in the context of both prior immune and non-immune-mediated reactions was safe and successful in improving the uptake of first-line Pneumocystis pneumonia prophylaxis in renal transplant recipients.

Topics: Female; Follow-Up Studies; Humans; Kidney Transplantation; Male; Middle Aged; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

Antimicrobial prophylaxis is indicated to prevent Pneumocystis jirovecii pneumonia (PJP) in profoundly immunosuppressed children. The incidence of PJP infection in children with chronic glucocorticoid exposure is unknown, and PJP prophylaxis has been associated with adverse events. We hypothesized that PJP infection is rare in children without human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), cancer, or a transplant history who are using chronic glucocorticoids and that those exposed to PJP prophylaxis are more likely to experience a cutaneous hypersensitivity reaction or myelosuppression than unexposed patients.. This study involved a retrospective cohort from the Clinformatics Data Mart Database (OptumInsight, Eden Prairie, MN). We identified patients ≤18 years of age who received at least 2 prescriptions for a systemic glucocorticoid within a 60-day period and excluded patients with a history of PJP infection, an oncologic diagnosis, transplant, or HIV/AIDS. PJP prophylaxis exposure was identified by using national drug codes. Cutaneous hypersensitivity reaction or myelosuppression was identified by using International Classification of Diseases, 9th Revision (ICD-9), codes. We used a discrete time-failure model to examine the association between exposure and outcome.. We identified 119399 children on glucocorticoids, 10% of whom received PJP prophylaxis. The incidences of PJP were 0.61 and 0.53 per 10000 patient-years in children exposed and those unexposed to PJP prophylaxis, respectively. In a multivariable model, trimethoprim-sulfamethoxazole was associated with cutaneous hypersensitivity reaction (odds ratio, 3.20; 95% confidence interval, 2.62-3.92) and myelosuppression (odds ratio, 1.85; 95% confidence interval, 1.56-2.20).. PJP infection was rare in children using glucocorticoids chronically, and PJP prophylaxis-associated cutaneous hypersensitivity reactions and myelosuppression are more common. The use of PJP chemoprophylaxis in children without HIV/AIDS, cancer, or a transplant history who are taking glucocorticoids chronically should be considered carefully.

Topics: Adolescent; Antifungal Agents; Bone Marrow Diseases; Child; Child, Preschool; Drug Eruptions; Female; Glucocorticoids; Humans; Immunocompromised Host; Incidence; Infant; Infant, Newborn; Male; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the efficacy and safety of trimethoprim/sulfamethoxazole (TMP-SMX) as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatic diseases receiving high-dose steroids.. The study included 1522 treatment episodes with prolonged (≥4 weeks) high-dose (≥30 mg/day prednisone) steroids in 1092 patients over a 12-year period. Of these, 262 treatment episodes involved TMP-SMX (prophylaxis group) while other episodes involved no prophylaxis (control group). Differences in 1-year PCP incidence and its mortality between the two groups were estimated using Cox regression. To minimise baseline imbalance, propensity score matching was performed and efficacy outcome was mainly assessed in the postmatched population (n=235 in both groups).. During a total of 1474.4 person-years, 30 PCP cases occurred with a mortality rate of 36.7%. One non-fatal case occurred in the prophylaxis group. TMP-SMX significantly reduced the 1-year PCP incidence (adjusted HR=0.07(95% CI 0.01 to 0.53)) and related mortality (adjusted HR=0.08 (95% CI 0.0006 to 0.71)) in the postmatched population. The result of the same analysis performed in the whole population was consistent with that of the primary analysis. Incidence rate of adverse drug reactions (ADR) related to TMP-SMX was 21.2 (14.8-29.3)/100 person-years. Only two serious ADRs (including one Stevens-Johnson syndrome case) occurred. The number needed to treat for preventing one PCP (52 (33-124)) was lower than the number needed to harm for serious ADR (131 (55-∞)).. TMP-SMX prophylaxis significantly reduces the PCP incidence with a favourable safety profile in patients with rheumatic disease receiving prolonged, high-dose steroids.

Topics: Adult; Antifungal Agents; Female; Glucocorticoids; Humans; Incidence; Male; Middle Aged; Pneumonia, Pneumocystis; Propensity Score; Retrospective Studies; Rheumatic Diseases; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

A 67-year-old man was admitted to our hospital complaining of dry cough. Chest computed tomography showed diffuse infiltrates and ground-glass opacities in the bilateral lung fields. Transbronchial lung biopsy specimens showed alveoli filled with yeast-like fungi. With a diagnosis of pneumocystis pneumonia (PCP), he was given oral sulfamethoxazole/trimethoprim, to which he responded well. However, seven months later, PCP relapsed. Analyses revealed a low bronchoalveolar lavage fluid CD4/CD8 ratio of 0.04 and CD4+ lymphocytopenia (250/μL). Despite intensive work-up, we were unable to detect the underlying cause of CD4+ lymphocytopenia; therefore, a final diagnosis of idiopathic CD4+ T-lymphocytopenia was made.

Topics: Acquired Immunodeficiency Syndrome; Aged; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Humans; Lung; Male; Pneumocystis; Pneumonia, Pneumocystis; T-Lymphocytopenia, Idiopathic CD4-Positive; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Arthritis, Rheumatoid; Glucocorticoids; Humans; Pneumocystis; Pneumonia, Pneumocystis; Rheumatic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Nocardial infections have been rare after allogeneic hematopoietic stem cell transplantation (HSCT). We report 10 recent cases of late-onset nocardiosis (median time of onset of 508 days after transplantation) primarily in patients on high doses of corticosteroids for graft-versus-host disease. All 10 patients had pulmonary infection caused by Nocardia species susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). At time of diagnosis 8 of 10 patients were not receiving TMP-SMX for prophylaxis of Pneumocystis jiroveci pneumonia (PJP; 7 on atovaquone, 1 on i.v. pentamidine). After the initiation of atovaquone prophylaxis for PJP in place of TMP-SMX for many UCLA allogeneic HSCT patients in 2012, 9 cases of nocardiosis occurred in 411 patients (2.2%) over the next 6 years (2012 to 2017) compared with only 1 case in 575 patients (0.17%) during the previous 12 years (2000 to 2011). Although there were no deaths directly related to nocardial infection treated primarily with TMP-SMX, overall mortality in this group of patients was 40%. Based on this experience, the use of atovaquone for PJP prophylaxis in place of TMP-SMX may be associated with an increased risk for previously rare nocardial infections after allogeneic HSCT.

Topics: Adult; Aged; Allografts; Atovaquone; Female; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Male; Middle Aged; Nocardia Infections; Pneumonia, Pneumocystis; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

Immunosuppressant medications (ISPs) increase the occurrence of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients. The prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) for PCP is effective but has serious adverse effects and so should be selectively used for patients at high risk. The aims of this study were to clarify the risk factors for PCP in RA patients and to establish the indications for administering TMP/SMX.. This retrospective cohort study analyzed data from 2640 patients (2010-2014) diagnosed as having RA who had not received a prophylactic administration of TMP/SMX. The risk factors for PCP were evaluated by comparing the clinical parameters between patients with PCP (PCP group, n = 19) and those without (non-PCP group, n = 2621).. The PCP group was older (70 vs. 64 years), received higher doses of prednisolone (6.2 vs. 2.4 mg/d) and methotrexate (7.7 vs. 5.2 mg/wk), and had a greater number of ISPs (1.3 vs. 0.8) (p < 0.05). We stratified the PCP risk using a scoring system based on odds ratios (ORs) calculated for these parameters (methotrexate ≥6 mg/wk OR = 4.5, 1 point; age ≥65 years, OR = 3.7, 1 point; ≥2 ISPs, OR = 3.7, 1 point; prednisolone ≥5 mg/d, OR = 12.4, 3 points). The incidence of PCP among patients scoring 0 to 2 points was 0.04%; 3 to 4 points, 2.3%; and 5 points or more, 5.8%.. The prophylactic administration of TMP/SMX for PCP is recommended for RA patients who score at least 5 points with our system.

Topics: Aged; Arthritis, Rheumatoid; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Drug Hypersensitivity Syndrome; Glomerulonephritis, IGA; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pneumonia, Pneumocystis; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Prednisolone; Skin; Trimethoprim, Sulfamethoxazole Drug Combination

We present a case of a 57-year-old woman who contracted

Topics: Anti-Bacterial Agents; Arthritis, Rheumatoid; Diagnosis, Differential; Drug Combinations; Etanercept; Female; Humans; Immunosuppressive Agents; Injections, Subcutaneous; Intensive Care Units; Methotrexate; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography, Thoracic; Respiration, Artificial; Respiratory Insufficiency; Sputum; Steroids; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Autoimmune Diseases of the Nervous System; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Pneumonia, Pneumocystis; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Intravenous; Aerosols; Antifungal Agents; Child, Preschool; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Infant; Infant, Newborn; Male; Nervous System Neoplasms; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

An outbreak of Pneumocystis pneumonia (PCP) in liver transplant recipients occurred between 2009 and 2011 at the Beaujon University Hospital just after immediate-release tacrolimus was replaced by extended-release tacrolimus. We conducted a retrospective study to analyze the transmission mode of Pneumocystis, the role of the change in the immunosuppressive regimen, and the factors associated with PCP.. To analyze transmission, we built a transmission map. Two control groups were built. First, to assess the role of the change from tacIR to tacER, cases were matched to controls transplanted before 2009 (tacIR control group). Tacrolimus trough concentrations were compared between the 2 groups. Then, to assess factors associated with PCP, each PCP case was matched to 2 control patients: the one transplanted just before and the one just after (PCPAsFact control group). No PCP prophylaxis was given to any patient.. Fifteen cases of PCP were recorded. A contact between a case and a patient who developed PCP afterward was identified in 4 occasions. The comparison of tacrolimus trough concentrations did not conclude to a difference in the exposure to the drug. Lymphopenia was the only factor independently associated with the occurrence of PCP (odds ratio 0.78, 95% confidence interval 0.61-0.99, P = .04).. Our results suggest that patient-to-patient transmission was not the main mode of transmission of PCP. We found no evidence that the switch from tacIR to tacER led to an overexposure to tacrolimus. Our results suggest the possibility of targeted prophylaxis in immunosuppressed liver transplant recipients.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Disease Outbreaks; Female; France; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Chronic Disease; Crystallization; Humans; Kidney Diseases; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Dapsone may be used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in hematology patients receiving immunosuppressive therapy or after hematopoietic stem cell transplant (HSCT) in the setting of trimethoprim-sulfamethoxazole (TMP-SMX) adverse drug reaction (ADR) history. Dapsone-induced hematological toxicities such as oxidative hemolysis may limit use in these patients and modern assessments of dapsone allergy cross-reactivity in non-HIV patients with a sulfonamide allergy are largely absent. The aim of this single-centre, retrospective study was to describe dapsone usage in hematology patients requiring PJP prophylaxis, including HSCT recipients, over a 12-month period in terms of indications, incidence of dapsone-attributed oxidative hemolysis, and immune cross-reactivity in those previously labeled with a sulfonamide allergy, as well as describing potential opportunities for first-line TMP-SMX PJP prophylaxis reintroduction. Of 24 patients meeting the study inclusion criteria, 12 (50%) were receiving dapsone PJP prophylaxis post-HSCT. No cases of breakthrough PJP infection were noted. Sixteen patients (67%) were initiated on dapsone to avoid the perceived risk of further myelosuppression with TMP-SMX and five patients (21%) because of prior delayed immune-mediated allergy to TMP-SMX. None experienced rash with dapsone therapy. Six patients (25%) were successfully rechallenged on TMP-SMX, including one patient with prior TMP-SMX-associated rash. Four (17%) patients had confirmed oxidative hemolysis, all resulting in dapsone cessation. Dapsone PJP prophylaxis in hematology patients was effective and safe, with nonlife threatening dapsone-related hemolysis noted in a small number. An absence of sulfonamide allergy cross-reactivity was noted, suggesting greater TMP-SMX rechallenges or desensitization could be considered in those receiving dapsone.

Topics: Aged; Anemia, Hemolytic; Anti-Infective Agents; Antibiotic Prophylaxis; Dapsone; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hemolysis; Humans; Immunosuppression Therapy; Male; Middle Aged; Oxidative Stress; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Although Pneumocystis jiroveci pneumonia (PCP) is a frequent manifestation of acquired immune deficiency syndrome (AIDS), the granulomatous form is uncommon. Here, we present an unusual case of granulomatous PCP consequent to immune reconstitution inflammatory syndrome (IRIS) after highly active antiretroviral therapy. A 36-year-old woman with human immunodeficiency virus (HIV) presented with cough and dyspnea that were attributed to typical PCP associated with AIDS. She was successfully treated with antibiotic, steroid, and antiretroviral therapies. After six months, however, she presented with consolidating lung lesions caused by bronchial obstruction from PCP granulomatous disease. Although antibiotics were ineffective, the effectiveness of steroid therapy suggested a diagnosis of granulomatous IRIS caused by persistent PCP antigens. Physicians should strongly suspect PCP in HIV-positive patients with nodular lung lesions and must remain aware that these lesions, if immune in origin, might not respond to antimicrobial therapy.

Topics: Adult; Anti-Infective Agents, Urinary; Antiretroviral Therapy, Highly Active; Bronchoscopy; Female; Granuloma, Respiratory Tract; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Immunocompromised Host; Lung; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Descriptive data on Pneumocystis jirovecii pneumonia (PJP) in solid organ transplant recipients (SOTr) in the era of routine Pneumocystis-prophylaxis are lacking.. All adult SOTr between 2008 and 2016 were included. PJP was diagnosed based on consensus guidelines. Early-onset PJP was defined as PJP within the first-year-post-transplant.. 41/2842 SOTr (1.4%) developed PJP (incidence rate: 0.01/1000 person-days) at a mean of 493-days post-transplant: 21 (51.2%) early vs 20 (48.8%) late-onset PJP. 2465 (86.7%) SOTr received Pneumocystis-prophylaxis for a mean 316 days. PJP incidence was 0.001% and 0.003% (log-rank < 0.001) in SOTr with and without Pneumocystis-prophylaxis, respectively. PJP was an early event in 10/12 (83.3%) SOTr who did not receive Pneumocystis-prophylaxis and developed PJP, compared to those patients who received prophylaxis (11/29, 37.9%; P-value: 0.008). Among late-onset PJP patients, most cases (13/20, 65%) were observed during the 2nd year post-transplant. Age ≥65 years (OR: 2.4, P-value: 0.03) and CMV infection during the first 6 months post-SOT (OR: 2.5, P-value: 0.006) were significant PJP predictors, while Pneumocystis-prophylaxis was protective for PJP (OR: 0.3, P-value: 0.006) in the overall population. Most patients (35, 85.4%) were treated with trimethoprim-sulfamethoxazole for a mean 20.6 days. 1-year mortality was 14.6%.. In the Pneumocystis-prophylaxis-era, PJP remains a rare post-transplant complication. Most cases occurred post-PJP-prophylaxis-discontinuation, particularly during the second-year-post-transplant. Additional research may help identify indications for Pneumocystis-prophylaxis prolongation.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Female; Humans; Incidence; Male; Middle Aged; Mortality; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Prospective Studies; Switzerland; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pneumocystis jiroveci pneumonia (PJP) is a much-feared complication of the use of immunosuppressive drugs. There is no current consensus on the indications for PJP prophylaxis in patients with rheumatological diseases who are receiving higher-dose glucocorticoid treatment over a prolonged period. The decision on whether or not to administer prophylaxis depends primarily on the Number Needed to Treat (NNT) vs the Number Needed to Harm (NNH) of trimethoprim/sulfamethoxazole (TMP/SMX) or other forms of prophylaxis. A recent retrospective study from South Korea supports the efficacy and safety of TMP/SMX for patients using ≥ 30 mg prednisone for > 1 month, especially in those with high-risk disease or other risk factors. Surveillance of regional and national PJP incidence, along with possible predictors, may help in gaining a better understanding of risk groups and in drawing up a regional, or preferably national, protocol.

Topics: Anti-Bacterial Agents; Glucocorticoids; Humans; Pneumonia, Pneumocystis; Prednisone; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Cortex Hormones; Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Cortex Hormones; Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Bacterial Agents; Female; Humans; Immunologic Factors; Male; Middle Aged; Pemphigus; Pneumonia, Pneumocystis; Retrospective Studies; Rituximab; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination

An outbreak of Pneumocystis jirovecii pneumonia (PCP) occurred among heart transplant recipients (HTR) at the outpatient clinic of a university hospital, from March to September 2015. Clinical, therapeutic, biological, and molecular data were analyzed to determine its origin and control the outbreak.. Clinical and biological data regarding all HTR followed in the outpatient clinic were collected. PCP diagnosis was based on microscopy and real-time polymerase chain reaction (PCR). Investigations were performed by building a transmission map, completed by genotyping Pneumocystis isolates and by a control of chemoprophylaxis observance. Asymptomatic exposed patients were screened for colonization using real-time PCR.. Among 124 HTR, 7 PCP cases were confirmed. Screening identified 3 additional patients colonized by P. jirovecii. All patients were cured, and no further cases were identified after trimethoprim-sulfamethoxazole prophylaxis was introduced in the entire cohort. Genotyping demonstrated the same strain in all PCP cases and colonized patients. All cases were linked with possible transmission chains from 2 possible index patients. Interhuman transmission was significantly associated with more frequent visits in the outpatient clinic. Six cases were receiving atovaquone as a prophylaxis. The occurrence of PCP was significantly associated with atovaquone prophylaxis.. This is the first outbreak with detailed molecular analysis in HTR so far. Genotyping and transmission chain confirmed interhuman transmission in all colonized/infected PCP cases. Outpatient clinic layout and high encounters probably caused this PCP cluster, which was controlled after systematic trimethoprim-sulfamethoxazole prophylaxis in exposed patients.

Topics: Adult; Aged; Atovaquone; Chemoprevention; Cross Infection; Disease Outbreaks; Female; Genotype; Heart Transplantation; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Kidney transplant recipients who are switched to atovaquone (ATO) from trimethoprim-sulfamethoxazole (TMP/SMX) for Pneumocystis jirovecii pneumonia (PJP) prophylaxis because of adverse events or complications may miss opportunities to be re-challenged with TMP/SMX, the first-line agent. This single-site, retrospective study assessed kidney transplant recipients for documented reasons for switching from TMP/SMX to alternate PJP prophylaxis and outcomes of TMP/SMX re-challenge. Out of 166 patients, 155 initially received TMP/SMX; of these, 31 were switched to ATO for various reasons. Fourteen patients receiving ATO were re-challenged with TMP/SMX; all were successfully re-initiated on TMP/SMX therapy. Most patients switched to ATO post kidney transplant secondary to non-hypersensitivity reasons should be re-challenged with TMP/SMX because of the advantages it provides over other agents.

Topics: Adult; Anti-Infective Agents; Antibiotic Prophylaxis; Atovaquone; Drug Substitution; Humans; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Complications; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pneumocystis Jirovecii (PJ) is regarded as an agent of fungal infection and in cases of pneumocystis pneumonia (PCP) in immune-compromised patients including cancer patients. It is not clear what kinds of cancer, treatments, and environment need prophylaxis for PCP. In this study, we have analyzed the detectability of PJ DNA from sputum, and discussed prophylaxis and risk factors regarding PCP.. A total of forty-nine materials (twenty-four from outpatients during cancer chemotherapies and twenty-five from healthy control subjects) was collected. Their PJ DNAs were amplified using nested PCR with specific primers of the PJ gene (the mitochondrial small subunit rRNA gene).. PJ DNA was detectable in 46% of specimens (sputum) from cancer patients during chemotherapies, and incidences of not significantly different among types of cancer and chemotherapy regimens. Prophylactic use of Sulfamethoxazole/Trimetoprim (ST) reduced the detection of PJ DNA. Detection of PJ DNA is not high among healthy non-smokers (20%) and high among healthy smokers (47%).. Prophylactic use of ST may be necessary for cancer patients during chemotherapies. Also, smoking may be associated with PJ colonization in the airway and air vesicles, and may increase the mortality rate for PCP. All patients undergoing cancer chemotherapies should cease smoking.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bronchoalveolar Lavage Fluid; DNA Primers; DNA, Fungal; Female; Genes, rRNA; Healthy Volunteers; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasms; Outpatients; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Respiratory System; Smokers; Sputum; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Child, Preschool; Consanguinity; Gene Expression; Guanine Nucleotide Exchange Factors; Homozygote; Humans; Male; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Severe Combined Immunodeficiency; Trimethoprim, Sulfamethoxazole Drug Combination

The echinocandins have shown anti-Pneumocystis jiroveci activity in nonhuman animal models; however, the corresponding human clinical experience has been rarely reported. We report a clinical picture of P jiroveci pneumonia (PJP) and determine the effects of concomitant therapy with echinocandins and trimethoprim (TMP)-sulfamethoxazole (SMZ).. We investigated a retrospective case series of heart transplantation (HT) recipients with PJP from July 1988 to December 2015. Recipient charts were reviewed for their demographic characteristics, underlying conditions, concomitant infections, PJP prophylaxis, TMP-SMZ dosages, adverse events, echinocandin use, oxygenation, and outcomes.. Eleven of 451 HT recipients developed PJP after a median duration of 2.8 years after transplantation. All 11 were treated with TMP-SMZ; 5 of them were treated with echinocandins added to the standard TMP-SMZ regimen. The longest interval between transplantation and PJP development was 16.3 years. The mortality rate was 33.3% in recipients receiving TMP-SMZ alone, whereas it was 20% in those receiving echinocandins as well. The most common side effects of TMP-SMZ include nausea and vomiting, metabolic acidosis, and hyperkalemia. Five recipients developed acute psychosis after a median duration of 6 days of TMP-SMZ therapy. The incidence of psychosis increased from 25% in recipients receiving TMP at ≤15 mg/kg/d to 100% in those receiving TMP at >15 mg/kg/d.. Echinocandins along with the standard TMP-SMZ regimen may effectively alleviate PJP developed after HT. The ideal prophylaxis duration is lifelong owing to the late onset of PJP. The typically intolerable adverse effects of TMP-SMZ therapy for PJP may necessitate dosage adjustments in some cases.

Topics: Adult; Aged; Antifungal Agents; Drug Therapy, Combination; Echinocandins; Female; Heart Transplantation; Humans; Immunocompromised Host; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Complications; Psychoses, Substance-Induced; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antibiotic Prophylaxis; Antifungal Agents; Child; Humans; Immunocompromised Host; Male; Methemoglobinemia; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The antibiotic, trimethoprim-sulfamethoxazole (TMP-SMX), is generally used for prophylaxis in HIV individuals to protect them from Pneumocystis jiroveci infection. Long-term use of TMP-SMX develops drug resistance among bacteria in HIV patients. The study was aimed to detect the TMP-SMX resistance genes among gram-negative bacteria from HIV patients. TMP-SMX-resistant isolates were detected by the Kirby-Bauer disc diffusion method. While TMP resistance genes such as dfrA1, dfrA5, dfrA7, and dfrA17 and SMX resistance genes such as sul1 and sul2 were detected by multiplex PCR, class 1 and class 2 integrons were detected by standard monoplex PCR. Of the 151 TMP-SMX-resistant bacterial isolates, 3 were positive for sul1 alone, 48 for sul2 alone, 11 for dfrA7 alone, 21 for sul1 and sul2, 1 for sul1 and dfrA7, 23 for sul2 and dfrA7, 2 for sul2 and dfrA5, 41 for sul1, sul2, and dfrA7, and 1 for sul2, dfrA5, and dfrA7. Of 60 TMP-SMX-resistant isolates positive for integrons, 44 had class 1 and 16 had class 2 integrons. It was found that the prevalence of sul genes (n = 202; p < 0.001) was higher compared with dfr genes (n = 80; p < 0.001), and 87.4% (n = 132; p < 0.001) of TMP-SMX-resistant isolates also were positive for β-lactamase production. This type of study is reported for the first time from HIV patients in India. Therefore, this study indicates that dissemination of TMP-SMX resistance genes and class 1 and class 2 integrons along with β-lactamase production among gram-negative bacteria in HIV patients will certainly make their treatment to bacterial infections more complicated in clinical settings.

Topics: Anti-Bacterial Agents; beta-Lactamases; Coinfection; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Gene Expression Regulation, Bacterial; Genes, Bacterial; HIV Infections; Humans; India; Integrons; Pneumocystis carinii; Pneumonia, Pneumocystis; Primary Prevention; Trimethoprim, Sulfamethoxazole Drug Combination

Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP). The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions and to have a twice-longer duration of mechanical ventilation if mechanically ventilated. Specific genotypes did not associate with death, which occurred in none of the HIV-infected patients and in 50% of the non-HIV-infected patients. Chile has a high prevalence of DHPS mutations, which were presumably acquired through interhuman transmission because patients were not on sulfa prophylaxis. These results contrast with the low prevalence observed in other Latin American countries with similar usage of sulfa drugs, suggesting that additional sources of resistant genotypes may be possible. The twice-longer duration of mechanical ventilation in patients with mutant DHPS genotypes suggests a decreased efficacy of TMP-SMX and warrants collaborative studies to assess the relevance of DHPS mutations and further research to increase therapeutic options for PCP.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Caspofungin; Chile; Dapsone; Dihydropteroate Synthase; Echinocandins; Female; Humans; Lipopeptides; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PJP) is a common infection among susceptible patients with compromised immune function and can lead to life-threatening complications without prompt recognition and appropriate treatment. Clinicians should be aware that patients can develop severe infection even while receiving approved prophylactic medications for PJP. Furthermore, atypical radiographic findings, such as the cavitary lung lesions found in the patient in this case report, can make the diagnosis even more challenging.

Topics: Bronchoalveolar Lavage Fluid; Fatal Outcome; Humans; Immunocompromised Host; Lung; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is recognized as an opportunistic pathogen. In recent years, human-to-human transmission of P. jirovecii has been demonstrated. However, outbreaks of P. jirovecii infections are not well defined because the epidemiological setting that facilitates transmission is not fully understood. This article describes two outbreaks of P. jirovecii pneumonia (PCP) in renal transplant patients in the West of Scotland. In total, 25 patients in two geographically contiguous locations were affected. Allele B was identified as the dominant type, along with allele A3. It was not possible to determine the exact reason for clustering of cases, although the outpatient clinic setting featured in one of the outbreaks. The outbreaks ceased with the use of trimethoprim-sulphamethoxazole prophylaxis; the target populations that received prophylaxis were different in the two outbreaks. Infection control teams should be alert to the possibility of outbreaks of PCP.

Topics: Adult; Antifungal Agents; Chemoprevention; Cluster Analysis; Disease Outbreaks; Female; Genotype; Humans; Kidney Transplantation; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Scotland; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

To study dapsone in comparison with trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis jiroveci (PJP) prophylaxis in children with acute lymphoblastic leukemia (ALL).. A retrospective study with a prospective follow-up.. Pediatric ALL patients diagnosed between May 2009 and May 2014, who are still receiving or have completed their maintenance chemotherapy. Patients who completed chemotherapy were prospectively followed up for neutropenia.. TMP/SMX was used as the initial PJP prophylaxis. An alternative drug was indicated if the patient remained cytopenic for >3 weeks. Average absolute neutrophilic count (ANC), average % of oral mercaptopurine (6-MP), and methotrexate doses were calculated over a period of 6 months before and after shifting to dapsone.. Sixty-two ALL patients were eligible for analysis. Twenty-four patients (38.7%) received TMP/SMX for PJP prophylaxis, whereas 34 patients received Dapsone (54.8%). Only 3 patients received IV pentamidine (4.8%), whereas 1 patient (1.6%) received atovaquone. The incidence of prophylaxis failure was 1/1041 months on TMP/SMX and 1/528 months on dapsone. After shifting to dapsone, patients maintained significantly higher ANC (1.46±0.46 vs. 1.17±0.40, P=0.0053), and received significantly higher doses of 6-MP (62.61%±11.45 vs. 57.45±10.14, P=0.0081) and methotrexate (64.9%±14.29 vs. 56.5%±9.9, P=0.0176), with a significantly shorter duration of chemotherapy interruption (1.94±1.2 vs. 3.25±1.29 wk, P=0.0002).. Dapsone for PJP prophylaxis in ALL allowed patients to maintain higher ANC and to receive higher doses of chemotherapy, while maintaining a low incidence of PJP breakthrough infection.

Topics: Antibiotic Prophylaxis; Child; Child, Preschool; Dapsone; Female; Humans; Infant; Male; Neutropenia; Pneumocystis carinii; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Although it is well-established that children undergoing allogeneic stem cell transplants and treatment for leukemia should be offered prophylaxis against Pneumocystis jirovecii pneumonia, the risk for children with solid malignancies is less certain. This guideline has been developed with the aim of standardizing practice and optimizing the benefit versus risk of prophylactic medication in this group of patients. P. jirovecii pneumonia has a high mortality rate even with prompt antimicrobial treatment. Since prophylaxis with co-trimoxazole is safe, effective, and inexpensive, we suggest that all children with malignancies undergoing immunosuppressive therapy are offered prophylaxis unless there are clear contraindications.

Topics: Antibiotic Prophylaxis; Child; Humans; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

We report a patient with AIDS who had an anaphylactic-like reaction from trimethoprim-sulfamethoxazole. Clinical suspicion of anaphylaxis should be considered in patients presenting with fever, hypotension, eosinophilia, rash, flushing or pulmonary infiltrates after initial exposure and re-exposure to the medication. This case highlights the need for healthcare professionals to be reminded of the association between this unusual antibiotic reaction resembling sepsis and HIV disease.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anaphylaxis; Anti-Bacterial Agents; Drug Hypersensitivity; Female; Fever; Humans; Pneumonia, Pneumocystis; Transgender Persons; Trimethoprim, Sulfamethoxazole Drug Combination

Reversible myoclonus, tremor, and asterixis induced by high dose trimethoprim-sulfamethoxazole.. The patient was a 66-year-old male with T9 AIS(1) C quadriplegia secondary to spinal cord compression by a tumor due to large B cell lymphoma. Subsequent to tumor resection and chemotherapy, the patient was discovered to have Pneumocystis jiroveci pneumonia (PJP). Once started on high dose trimethoprim-sulfamethoxazole (TMP-SMX) therapy (15.6 mg/kg/day of trimethoprim) for the treatment of PJP, he displayed bilateral upper extremity myoclonic jerks at rest, asterixis, and postural tremor. Symptoms resolved once TMP-SMX therapy was discontinued.. Myoclonus, asterixis, and tremor have been linked to high dose TMP-SMX therapy as a toxic side effect. Our patient's symptoms did improve with levetiracetam therapy, but did not fully resolve until TMP-SMX was discontinued.. This is thought to be the first reported case of reversible myoclonus, tremor, and asterixis induced by high dose TMP-SMX in the spinal cord injury population. Early recognition of TMP-SMX induced complications were of key importance as they negatively impacted the rehabilitation process. We also recommend consideration of symptomatic treatment with levetiracetam for the duration of required TMP-SMX therapy as it appeared to mitigate the severity of our patient's movement disorders.

Topics: Aged; Anti-Bacterial Agents; Dyskinesia, Drug-Induced; Humans; Male; Pneumonia, Pneumocystis; Spinal Cord Injuries; Trimethoprim, Sulfamethoxazole Drug Combination

Reactivation of latent infection is considered to be the main mechanism underlying the development of Pneumocystis pneumonia in immunosuppressed patients. We retrospectively assessed the effects of prophylactic administration of sulfamethoxazole-trimethoprim on the development of P. pneumonia and airway colonization with P. jirovecii in patients undergoing examinations to diagnose or rule out P. pneumonia. Polymerase chain reaction was performed to detect P. jirovecii in bronchoalveolar lavage fluid or sputum of 60 consecutive patients between 2004 and 2012. No patients who received the prophylactic administration of sulfamethoxazole-trimethoprim (n = 10) developed P. pneumonia or demonstrated airway colonization with P. jirovecii, and none of the patients who developed P. pneumonia (n = 11) or showed colonization (n = 9) had received prophylactic treatment. Furthermore, 20 (40%) of 50 patients without prophylactic treatment showed positive results on the P. jirovecii DNA polymerase chain reaction, but all 10 patients who had prophylactic treatment showed negative results (Fisher's exact test, P = 0.02). Therefore, the prophylactic administration of sulfamethoxazole-trimethoprim has potential to be effective in preventing P. pneumonia as well as eliminating airway colonization with P. jirovecii. Further studies targeting large cohorts of patients with a variety of underlying diseases are required to develop recommendations regarding the prophylactic administration of sulfamethoxazole-trimethoprim.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Aged, 80 and over; Antifungal Agents; Bronchoalveolar Lavage Fluid; Female; Hematologic Neoplasms; Humans; Immunocompromised Host; Lung; Lung Diseases, Interstitial; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Pre-Exposure Prophylaxis; Retrospective Studies; Sputum; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Antiretroviral Therapy, Highly Active; Carcinoma, Non-Small-Cell Lung; Cisplatin; Emtricitabine; Female; Heterocyclic Compounds, 3-Ring; HIV Infections; HIV-1; Humans; Lung Neoplasms; Middle Aged; Oxazines; Pemetrexed; Piperazines; Pneumocystis carinii; Pneumonia, Pneumocystis; Pyridones; Tenofovir; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

The recommended treatment of Pneumocystis jirovecii pneumonia (PCP) is high-dose trimethoprim-sulfamethoxazole (TMP-SMX) in an equivalent of TMP 15-20 mg/kg/day and SMX 75-100 mg/kg/day for 2 or 3 weeks. High rates of adverse events are reported with this dose, which raises the question if lower doses are possible.. All adult patients diagnosed with PCP in various immune dysfunctions and treated with TMP-SMX between January 1, 2003 and July 1, 2013 in a tertiary university hospital were included. Per institutional protocol, patients initiated treatment on intermediate-dose TMP-SMX (TMP 10-15 mg/kg/day) and could be stepped down to low-dose TMP-SMX (TMP 4-6 mg/kg/day) during treatment. Clinical variables at presentation, relapse rate and mortality rates were compared between intermediate- and step-down treatment groups by uni- and multivariate analyses.. A total of 104 patients were included. Twenty-four patients (23 %) were switched to low-dose TMP-SMX after a median of 4.5 days (IQR 2.8-7.0 days). One relapse (4 %) occurred in the step-down group versus none in the intermediate-dose group. The overall 30-day mortality was 13 %. There was 1 death in the step-down group (4 %) compared to 13 deaths (16 %) in the intermediate-dose group.. We observed high cure rates of PCP by treatment with intermediate-dose TMP-SMX. In addition, a step-down strategy to low-dose TMP-SMX during treatment in selected patients appears to be safe and does not compromise the outcome of treatment.

Topics: Aged; Antifungal Agents; Cohort Studies; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of numerous opportunistic infections. Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that can develop in immunocompromised individuals. Current prophylaxis for PJP includes trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, atovaquone, or inhaled pentamidine (PEN), often with varying breakthrough rates. The use of intravenous (IV) PEN for PJP prophylaxis has been evaluated in pediatric patients.. A single-institution retrospective review of electronic medical records was conducted for patients who underwent allo-HSCT between January 2001 and May 2013 and who had received at least 1 dose of IV PEN for PJP prophylaxis. Data collected included patient demographics, diagnosis, previous chemotherapy, pre-transplant conditioning regimen, other medications, microbiology test results, and clinical outcomes.. A total of 113 patients were included in the study. The median number of PEN doses administered per patient was 3 (range 1-23). IV PEN was primary PJP prophylaxis in 74 of the patients (65%) and second-line prophylaxis in 39 (35%) post transplant, with the majority switching from oral TMP-SMX. Side effects of IV PEN administration were minimal. No patients who received IV PEN prophylaxis developed PJP infection. No case of PJP was seen in patients who received other agents for PJP prophylaxis.. This retrospective study showed that IV PEN is very effective and well-tolerated prophylaxis for PJP; IV PEN can be considered a favorable alternative for PJP in situations where other agents might be contraindicated. Our findings provide strong support for prospective studies of IV PEN for PJP prophylaxis in adult HSCT recipients.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Atovaquone; Child; Child, Preschool; Dapsone; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Male; Middle Aged; Opportunistic Infections; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Outbreaks ofPneumocystispneumonia have been described in renal transplant recipients. Aerosolized pentamidine is frequently used for prophylaxis in this setting. We report our experience with aerosolized pentamidine use in 56 renal transplant recipients. We found high rates of adverse reactions in patients with chronic respiratory disease.

Topics: Adult; Aerosols; Antifungal Agents; Bronchial Spasm; Female; Humans; Kidney Transplantation; Lung; Male; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Renal Insufficiency, Chronic; Respiratory Tract Diseases; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

The international guidelines recommend the administration of trimethoprim-sulfamethoxazole (TMP-SMX) as Pneumocystis jiroveci pneumonia (PJP) prophylaxis for six months after transplantation. The aim of this study is to evaluate the influence of TMP-SMX prophylaxis on the occurrence of asymptomatic bacteriuria (ASB) and urinary tract infections (UTIs) as cystitis and allograft pyelonephritis (AGPN) and its impact on the antimicrobial resistance pattern of causative microorganisms.. We have conducted a retrospective before-after study in adult renal allograft recipients with one year follow-up after transplantation. We compared the ("after") group that received TMP-SMX as PJP prophylaxis to the ("before") group that did not receive it.. In total, 343 renal allograft recipients were analysed, of whom 212 (61.8 %) received TMP-SMX as PJP prophylaxis. In this study, 63 (18.4 %) did only develop ASB without UTI, 26 (7.6 %) developed cystitis and 43 (12.5 %) developed AGPN. The remaining 211 (61.5 %) renal allograft recipients did not develop any bacteriuria at all. Multivariable Cox proportional regression analysis indicated that TMP-SMX as PJP prophylaxis was not associated with reduced prevalence of ASB (Hazard ratio (HR) = 1.52, 95 % CI = 0.79-2.94, p = 0.213), nor with reduced incidence of cystitis (HR = 2.21, 95 % CI = 0.76-6.39, p = 0.144), nor AGPN (HR = 1.12, 95 % CI = 0.57-2.21, p = 0.751). Among the group receiving TMP-SMX as PJP prophylaxis there was a trend was observed in increase of both amoxicillin (86 % versus 70 %) and TMP-SMX (89 % versus 48 %) resistance which already appeared within the first 30 days after TMP-SMX exposure.. Among renal allograft recipients, administration of TMP-SMX as PJP prophylaxis does not prevent ASB nor UTI, however it is associated with tendency towards increased amoxicillin and TMP-SMX resistance.

Topics: Adult; Anti-Bacterial Agents; Asymptomatic Diseases; Bacteriuria; Controlled Before-After Studies; Cystitis; Drug Resistance, Bacterial; Female; Follow-Up Studies; Humans; Kidney Transplantation; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Complications; Pyelonephritis; Retrospective Studies; Transplantation, Homologous; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Low-dose trimethoprim-sulfamethoxazole (TMP-SMX) is commonly used to prevent pneumocystis pneumonia in daily practice. Previous reports have shown a relationship between high- or standard-dose of TMP-SMX and hyperkalemia, however it remains unclear whether this is true for low-dose TMP-SMX. In this study we sought to determine the risk factors for hyperkalemia associated with low-dose TMP-SMX.. In this retrospective cohort study, 186 consecutive adult patients who received TMP-SMX as prophylaxis for pneumocystis pneumonia from January 2014 to January 2015 were evaluated. Data on the patients' age, gender, baseline estimated glomerular filtration rate (eGFR), baseline serum potassium, maximum serum potassium, duration reaching the maximal serum potassium level, dosage, and concomitant use of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB), β-blockers, non-steroidal anti-inflammatory drugs and potassium-sparing diuretics were retrospectively collected. Hyperkalemia was defined as a serum potassium level ≥5 mEq/L. Univariate and multivariate analyses were performed.. The median age of the patients was 66 years and 51.1% were men. Hyperkalemia associated with low-dose TMP-SMX was observed in 32 patients (17.2%). The median duration to reach the maximal serum potassium level was 12 days. The multivariate logistic regression analysis identified renal insufficiency to be a major risk factor for hyperkalemia associated with low-dose TMP-SMX (eGFR <60 mL/min/1.73 m(2), adjusted OR 4.62). Moreover, in the subpopulation of patients with renal insufficiency, ACEi/ARB use was considered to be a major risk factor for hyperkalemia (adjusted OR 3.96).. Renal insufficiency in concert with ACEi/ARB use is a major risk factor for hyperkalemia induced by low-dose TMP-SMX.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Female; Humans; Hyperkalemia; Male; Middle Aged; Pneumonia, Pneumocystis; Renal Insufficiency; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Adult T-cell leukemia/lymphoma (ATLL) is usually preceded by infection with human T-cell lymphotropic virus I (HTLV-I). Patients with ATLL frequently get opportunistic infections of the lungs, intestines, and central nervous system. Pneumocystis pneumonia is commonly known as an AIDS defining illness. Grocott's methenamine silver stain of bronchoalveolar lavage (BAL) samples obtained via bronchoscopy remain the gold standard for diagnosis. Pulmonary cryptococcosis is seen in patients with T-cell deficiencies and a diagnosis is made by culture of sputum, BAL, or occasionally of pleural fluid. We present the second case of coinfection with these two organisms in a patient with ATLL who was successfully treated with trimethoprim-sulfamethoxazole, corticosteroids, and fluconazole. We illustrate the need for high clinical vigilance for seeking out an additional diagnosis, especially in immunocompromised patients if they are not improving despite receiving appropriate treatment.

Topics: Adrenal Cortex Hormones; Anti-Infective Agents; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Fluconazole; Humans; Immunocompromised Host; Leukemia-Lymphoma, Adult T-Cell; Male; Middle Aged; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/sulfamethoxazole (TMP/SMX) is currently the most effective therapeutic agent for Pneumocystis jirovecii pneumonia (PJP) in patients with AIDS. The major drawback is the frequent occurrence of adverse reactions (ADRs).The current study was designed to determine the frequency and risk factors for TMP/SMX-related ADRs among patients with PJP and AIDS.. A retrospective study was conducted in adult patients with PJP and AIDS who were admitted to the Veterans General Hospital in, Kaohsiung, Taiwan between January 2006 and December 2011. Charts were reviewed to determine the effect of age, risk behaviors, severity of illness, viral load, CD4 cell counts, use of corticosteroids, and dosage and duration of TMP/SMX on ADRs during hospitalization. Patients who received TMP/SMX for ≤ 5 days or with an incomplete medical record were excluded. Multivariate logistic regression was used to calculate the hazard ratio (HR) for ADRs.. Fifty two of 75 patients with PJP and AIDS met the study criteria. Of these patients, 21/52 (40.3%) developed an ADR. Among the 21 patients who suffered an ADR, skin rash was noted in 10 (47.6%), liver function impairment in nine (42.9%), elevated creatinine in eight (38.1%), fever in four (19%), and gastrointestinal symptoms in three (14.3%). Most of the ADRs occurred within the 1(st) 2 weeks of TMP/SMX therapy. Cox proportional hazards analysis revealed that a daily dose of TMP/SMX of ≥ 16 mg/kg (HR, 3.8; 95% confidence interval, 1.40-10.35; p = 0.009) and age 34 years (HR, 4.30; 95% confidence interval, 1.52-12.14; p = 0.006) were independently associated with ADRs.. We found a high incidence of ADRs among patients with PJP and AIDS treated with TMP/SMX, and most involved the skin and liver. A daily dose of ≥ 16 mg/kg of TMP/SMX and age 34 years were independent risk factors for ADRs.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Anti-Bacterial Agents; Female; Humans; Logistic Models; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Proportional Hazards Models; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) is potentially fatal infectious complication in patients with rheumatoid arthritis (RA) during immunosuppressive therapy. Hospital survival due to human immunodeficiency virus-unrelated PCP reaches to 60%. The high mortality rate results from difficulties in establishing an early diagnosis, concurrent use of prophylactic drugs, possible bacterial coinfection. We herein report a case of PCP in RA patients who developed the architectural distortions of lung in spite of combined modality therapy.. A 73-year-old Japanese woman with RA was admitted with shortness of breath. Five weeks previously, she had been started on etanercept in addition to methotrexate (MTX). Chest computed tomography (CT) demonstrated diffuse ground glass opacities distributed throughout the bilateral middle to lower lung fields, and serum β-D-glucan was elevated. Bronchoalveolar lavage fluid revealed no P. jirovecii, but the organism was detected by polymerase chain reaction method. Trimethoprim/sulfamethoxazole was administered with methylprednisolone pulse therapy. However, the follow-up chest X-ray and chest CT demonstrated aggravation of the pneumonia with architectural distortions. Additional direct hemoperfusion with polymyxin B-immobilized fibers and intravenous cyclophosphamide therapy were insufficiently effective, and the patient died on day 25.. The architectural distortions of lung should be considered as a cause of death of PCP. For this reason, a high suspicion of this infectious complication must be kept in mind in order to establish an early diagnosis and treatment in patients with RA managed with MTX and biologics.

Topics: Acute Disease; Aged; Anti-Infective Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Disease Progression; Etanercept; Fatal Outcome; Female; Humans; Lung Diseases, Interstitial; Methotrexate; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymyxin B; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection that can lead to significant morbidity and mortality in immunocompromised pediatric hematology/oncology patients. Trimethoprim/sulfamethoxazole is the gold standard for prophylaxis. Intravenous (IV) pentamidine is the preferred second-line agent for PCP prophylaxis at our institution and is used first-line under certain circumstances. The purpose of this study is to evaluate the effectiveness and safety of IV pentamidine for PCP prophylaxis in pediatric hematology/oncology patients.. A retrospective analysis of pediatric hematology/oncology patients (N=121) who received ≥1 dose of IV pentamidine between January 2009 and July 2014 was conducted. Electronic health records were reviewed to determine baseline characteristics, rate of breakthrough PCP infection, characteristics of IV pentamidine use, and adverse events. The follow-up period was 6 months after the last reported IV pentamidine dose or the last recorded clinic visit/hospital admission.. No patients developed PCP during the entirety of their IV pentamidine course or during the follow-up period. Nineteen patients (16%) experienced adverse events and 5 of the 19 patients required discontinuation of IV pentamidine.. IV pentamidine is a safe, tolerable, and effective agent for PCP prophylaxis in pediatric hematology/oncology patients and may be considered a reasonable therapeutic alternative when trimethoprim/sulfamethoxazole cannot be used for PCP prophylaxis.

Topics: Administration, Intravenous; Adolescent; Antifungal Agents; Child; Child, Preschool; Female; Humans; Male; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Disease Progression; Drug Therapy, Combination; Emigrants and Immigrants; Germany; HIV Infections; Humans; Male; Medication Adherence; Middle Aged; Nigeria; Pneumonia, Pneumocystis; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) treatment for pneumocystis pneumonia (PCP) in patients with autoimmune diseases who developed PCP was conducted in a retrospective study of the following: dosage, frequency of side effects and persistence rate of TMP/SMX and prognosis of patients. Seven patients (two males and five females, mean age: 72 years) were hospitalized between April 1, 2013 and August 31, 2015, and their underlying diseases were rheumatoid arthritis (six patients) and microscopic polyangiitis (one patient). Moderate-dose TMP/SMX (TMP equivalent to TMP/SMX, average: 9.6 mg/kg/day, range: 5.1-12.5 mg/kg/day) was used for PCP treatment. As a result, patients experienced the following side effects: hyponatremia in five patients (71.4%), exanthema in four patients (57.1%), and thrombocytopenia in two patients (28.6%). Elevated creatinine level, increased blood pressure, malaise, and hyperkalemia were experienced by each patient. Six patients (85.7%) discontinued TMP/SMX treatment due to side effects, but once they had recovered, desensitization to TMP/SMX was used to treat them. Eventually, four patients were successfully treated with TMP/SMX (final persistence rate, 57.1%). Their prognoses were good, and no patients died for at least 60 days after admission. Moderate-dose TMP/SMX treatment for PCP in patients with autoimmune diseases who developed PCP may have therapeutic effects equal to high-dose TMP/SMX treatment, and therefore collecting more case studies is expected.

Topics: Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoimmune Diseases; Female; Humans; Immunocompromised Host; Male; Microscopic Polyangiitis; Middle Aged; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) is used as prophylaxis against Pneumocystis jiroveci during chemotherapy. Many groups recommend withholding TMP/SMX during high-dose methotrexate (HDMTX) for concerns that it will delay methotrexate clearance. We compared methotrexate exposure following HDMTX (NCT00549848) in 424 patients including 783 courses that were given concurrently and 602 courses that were not given concurrently with TMP/SMX. Among 176 patients (555 courses) on the low-risk arm (HDMTX=2.5 g/m/24 h), there was no difference in clearance (110.7 [1.8%] vs. 108.2 [0.9%] mL/min/m, P=0.3) nor in 42 hour methotrexate concentration (0.37 [5.1%] vs. 0.40 (5.0%) μM, P=0.23). Among 248 patients (830 courses) on the standard/high-risk arm (HDMTX ~5 g/m/24 h), there was slightly higher clearance (95.5 [1.4%] vs. 91.2 [0.8%] mL/min/m, P=0.005) in those receiving TMP/SMX, with no difference in the 42 hour methotrexate concentration (0.59 [4.1%] vs. 0.66 [4.2%] μM, P=0.06). There was no difference in neutrophil counts based on TMP/SMX during HDMTX (P=0.83). TMP/SMX also did not have a significant impact on myelosuppression of low-dose methotrexate (40 mg/m) given during continuation therapy among 230 patients enrolled on a prior study (NCT00137111). Thus, we found no evidence for an interaction between methotrexate and TMP/SMX given prophylactically.

Topics: Anti-Bacterial Agents; Drug Interactions; Humans; Methotrexate; Pneumocystis carinii; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Data on PCP in patients with glomerular disease are rare. The aim of this study was to assess the predictors of PCP development, the risk factors for mortality and the incidence of acute kidney injury (AKI) when high-dose trimethoprim-sulphamethoxazole (TMP-SMX) was used in patients with non-transplant glomerular disease.. Forty-seven patients with PCP, as confirmed by positive results for Pneumocystis jirovecii DNA or Pneumocystis jirovecii cysts tested by a methenamine silver stain between January 1, 2003, and December 30, 2012, were retrospectively investigated. The baseline characteristics of glomerular disease, clinical findings of PCP and renal parameters after treatment were collected. Predictors for PCP development and risk factors for mortality were determined using a multivariate logistic regression analysis.. All PCP patients exclusively received immunosuppressants. Baseline renal insufficiency [estimated glomerular filtration rate (eGFR) <60 mL/min·1.73 m. PCP is a fatal complication in patients with glomerular disease, and the use of immunosuppressants may be a basic risk factor for this infection. Underlying renal insufficiency and high renal pathology chronicity are the key risk factors for PCP in IgA nephropathy. TMP-SMX therapy remains an ideal choice because of high treatment response and frequently reversible kidney injury.

Topics: Acute Kidney Injury; Adult; Aged; Coinfection; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA; Glomerulosclerosis, Focal Segmental; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Renal Insufficiency, Chronic; Respiration, Artificial; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly prescribed antibiotic used at high doses for treatment of pneumocystis pneumonia and other infections. Trimethoprim is structurally related to the potassium-sparing diuretic amiloride and has been associated with hyperkalemia and hyponatremia through blocking of epithelial sodium channels in the distal nephron. The incidence of hyponatremia in hospitalized patients treated with high-dose TMP-SMX is unknown.. Analysis was restricted to 76 unique patients who received more than 8 mg/kg/d of TMP for ≥3 days. Mean starting serum sodium at time of TMP-SMX initiation was 138.4 ± 2.1 mEq/L. Fifty-five patients (72.3%) developed hyponatremia while on therapy, of which 43.6% (n = 24) were cases of serum sodium <130 mEq/L. Mean sodium at the time of nadir was 131.6 ± 5.1 mEq/L. Hyponatremia was noted, on average, 5.5 days after initiation of therapy, with more severe hyponatremia development among African American patients. Urine sodium concentrations were available for 40.0% (22/55) of incident hyponatremia cases, with mean urinary sodium of 104.8 ± 55.9 mEq/L. Hyponatremia often resolved within 3 weeks of drug discontinuation.. There is a high incidence (72.3%) of hyponatremia associated with the use of high-dose TMP-SMX among hospitalized patients. This is an overlooked and potentially reversible cause of hyponatremia.

Topics: Anti-Bacterial Agents; Female; Humans; Hyponatremia; Incidence; Inpatients; Logistic Models; Male; Middle Aged; New York City; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The 5th European Conference on Infections in Leukaemia (ECIL-5) meeting aimed to establish evidence-based recommendations for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in non-HIV-infected patients with an underlying haematological condition, including allogeneic HSCT recipients. Recommendations were based on the grading system of the IDSA. Trimethoprim/sulfamethoxazole given 2-3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults ( A-II: ) and children ( A-I: ) and should be given during the entire period at risk. Recent data indicate that children may benefit equally from a once-weekly regimen ( B-II: ). All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated. The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, >4 weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children. Additional indications are proposed depending on the treatment regimen.

Topics: Antifungal Agents; Chemoprevention; Hematologic Neoplasms; Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Stem Cell Transplantation; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

The initiation of systemic antimicrobial treatment of Pneumocystis jirovecii pneumonia (PCP) is triggered by clinical signs and symptoms, typical radiological and occasionally laboratory findings in patients at risk of this infection. Diagnostic proof by bronchoalveolar lavage should not delay the start of treatment. Most patients with haematological malignancies present with a severe PCP; therefore, antimicrobial therapy should be started intravenously. High-dose trimethoprim/sulfamethoxazole is the treatment of choice. In patients with documented intolerance to this regimen, the preferred alternative is the combination of primaquine plus clindamycin. Treatment success should be first evaluated after 1 week, and in case of clinical non-response, pulmonary CT scan and bronchoalveolar lavage should be repeated to look for secondary or co-infections. Treatment duration typically is 3 weeks and secondary anti-PCP prophylaxis is indicated in all patients thereafter. In patients with critical respiratory failure, non-invasive ventilation is not significantly superior to intubation and mechanical ventilation. The administration of glucocorticoids must be decided on a case-by-case basis.

Topics: Administration, Intravenous; Antifungal Agents; Clindamycin; Hematologic Neoplasms; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Minnesota; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

This study aimed to quantify the risks of Pneumocystis pneumonia (PCP) among adult T-cell leukaemia (ATL) patients without prophylaxis. We used hospital administrative data collected nationwide in Japan over 4 years. The research design was a retrospective cohort study. Subjects were 4369 patients diagnosed with ATL aged 18 years or older. The subjects were categorized into four treatment groups: no agent, chemotherapy, chemotherapy + steroids and steroids. We described the risks of PCP among ATL patients without prophylaxis. Risks of PCP were 3·2% for the no agent group, 9·7% for the chemotherapy group, 10·0% for the chemotherapy + steroids group and 16·6% for the steroids group. Logistic regression analyses showed that the chemotherapy, chemotherapy + steroids and steroids groups had significantly higher risk of PCP than did the no agent group [adjusted odds ratio (AOR) 3·30 (1·55-7·02), P = 0·002 for the chemotherapy group; AOR 3·35 (2·18-5·17), P < 0·001 for the chemotherapy + steroids group; AOR 6·12 (3·99-9·38), P < 0·001 for the steroids group]. In conclusion, the chemotherapy, chemotherapy + steroids and steroids groups had significantly higher risks of PCP. Prophylaxis for PCP among ATL patients being treated with chemotherapy, chemotherapy + steroids and steroids is highly recommended.

Topics: Adrenal Cortex Hormones; Aged; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Comorbidity; Cross Infection; Drug Synergism; Female; Humans; Japan; Leukemia-Lymphoma, Adult T-Cell; Male; Middle Aged; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Health Surveys; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; United Kingdom

Pneumocystis pneumonia (PCP) in solid organ transplant (SOT) recipients becomes rare in the immediate posttransplantation period thanks to generalized prophylaxis. We aimed to identify the predictive factors for PCP in the era of universal prophylaxis and to propose a strategy for preventing PCP beyond the first year after transplantation. In a retrospective case-control study, 33 SOT cases with PCP diagnosed between 2004 and 2010 were matched with two controls each to identify risk factors for PCP by uni- and multivariate analysis. All the patients benefited from 6 months of posttransplantation trimethoprim-sulfamethoxazole prophylaxis. Most PCP in SOT patients occurred during the second year posttransplantation (33%). By univariate analysis, age, nonuse of tacrolimus, total and CD4 lymphocyte counts, gamma-globulin concentration and cytomegalovirus (CMV) infection appeared to be PCP risk factors. In the final multivariate analysis, age (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI]: 1.3-10.4), CMV infection (OR: 5.2, 95% CI: 1.8-14.7) and total lymphocyte count (OR: 3.9, 95% CI: 1.4-10.7) were found to be independently associated with PCP. The second year posttransplantation appeared to be the new period of highest risk of PCP. Age, CMV viremia and lymphocytes were the most pertinent predictive criteria to evaluate the risk of PCP in clinical practice.

Topics: Antibiotic Prophylaxis; Antifungal Agents; Case-Control Studies; Cytomegalovirus; Cytomegalovirus Infections; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunocompromised Host; Male; Middle Aged; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Complications; Retrospective Studies; Risk Factors; Tissue Donors; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

Recent meta-analyses showed that antibiotic prophylaxis in patients with neutropenia after chemotherapy reduced the incidence of fever and mortality rate. Fluoroquinolones appear to be most effective and well tolerated. Thus, in April 2008, we changed our antibiotic prophylaxis regimen from cotrimoxazole/colistin (COT/COL) to the fluoroquinolone ciprofloxacin (CIP) in patients with acute myeloid leukemia (AML). The aim of this retrospective study was to compare efficacy and development of bacterial resistance with two different prophylaxis regimens over a time period of more than 4 years.. Induction chemotherapy courses given for AML during the antibiotic prophylaxis period with COT/COL (01/2006-04/2008) and CIP (04/2008-06/2010) were retrospectively analyzed with a standard questionnaire.. Eighty-five courses in the COT/COL group and 105 in the CIP group were analyzed. The incidence of fever was not significantly different (COT/COL 80 % vs CIP 77 %; p = 0.724). Also, the rate of microbiologically documented infections was nearly the same (29 vs 26 %; p = 0.625). In addition, there was no significant difference in the incidence of clinically documented infections (11 vs 19 %; p = 0.155) or in the rates of detected gram-positive and gram-negative bacteria. Of note, there was no increase in resistance rates or cases with Clostridium difficile-associated diarrhea in the CIP group.. The antibiotic prophylaxis with CIP compared to COT/COL in AML was similarly effective with no increase in bacterial resistance. COT/COL may have the advantages of providing additional prophylaxis against Pneumocystis jirovecii pneumonia and leaving fluoroquinolones as an additional option for treatment of febrile neutropenia.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Agents; Bacterial Infections; Ciprofloxacin; Clostridioides difficile; Colistin; Diarrhea; Drug Resistance, Bacterial; Enterocolitis, Pseudomembranous; Female; Fever; Fluoroquinolones; Humans; Incidence; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination

Indications for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in patients with autoimmune disease remain unclear. We aimed to determine (1) the incidence of PCP in patients with autoimmune disease in general, in a clinical setting where prophylaxis is not routine, and (2) whether high-dose glucocorticoid (≥30 mg oral prednisolone or equivalent per day) is a risk factor for PCP infection.. A retrospective review of the medical records of patients with autoimmune diseases hospitalized to a tertiary center over a 5-year study period was carried out. Patient demographics, mean glucocorticoid dose (in the last 1 month), and the outcomes of patients who developed PCP were analyzed.. The incidence rate of PCP infection was 75 per 100,000 patients per year. The in-hospital mortality was 50%, and all those who died were on high-dose glucocorticoid at the time of PCP diagnosis. There was a significant difference between the occurrence of PCP in patients who were on high-dose vs non-high-dose glucocorticoid (df = 1, P = 0.009), with a relative risk of 19 (P = 0.010; 95% confidence interval, 2.0-182.8). The mean oral prednisolone dose of patients who developed PCP and those who did not were 55.5 versus 10.7 mg, respectively, P = 0.002.. High-dose glucocorticoid may be associated with an increased risk of PCP infection in patients with autoimmune diseases.

Topics: Adult; Aged; Anti-Infective Agents; Autoimmune Diseases; Female; Glucocorticoids; Humans; Incidence; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisolone; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

The benefit of prophylaxis for Pneumocystis jirovecii pneumonia (PJP) is well documented in immunocompromised patients, particularly those with HIV and/or AIDS; therefore, guidelines dictate this as standard of care. However, there is a paucity of literature regarding those without HIV and/or AIDS who are potentially predisposed to PJP, including patients with sarcoidosis, cryptogenic organizing pneumonia, interstitial lung disease, asthma and chronic obstructive pulmonary disease, who may require high dose of prolonged corticosteroids for disease maintenance or to prevent relapses. In this review, the authors examine the available literature regarding prophylaxis in these groups, elaborate on the pathogenesis of PJP, when to suspect PJP in these patients, as well as explore current recommendations that guide clinical practice regarding implementation of PJP prophylaxis, namely with trimethoprim/sulfamethoxazole being the preferred agent. In summary, the role of PJP prophylaxis in non-HIV patients on chronic steroids remains controversial. The authors present a review of the literature to provide better guidance to the clinician regarding the need to initiate PJP prophylaxis in this patient population.

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antibiotic Prophylaxis; Drug Administration Schedule; Humans; Immunocompromised Host; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Risk Factors; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Diaphenylsulfone (DDS: Dapsone) is used for Pneumocystis pneumonia (PCP) prophylaxis, and methemoglobinemia has rarely been reported as a side effect of DDS. We herein report two cases of DDS-related methemoglobinemia in an 81-year-old man with organizing pneumonia and an 84-year-old woman with eosinophilic pneumonia under treatment with prednisolone. Both patients initially received trimethoprim/sulfamethoxazole for PCP prophylaxis and were switched to DDS due to side effects and subsequently exhibited a clinically unexplainable decrease in SpO2. Methemoglobinemia was diagnosed based on the findings of arterial blood gas analyses. In both cases, the methemoglobinemia improved after discontinuing DDS.

Topics: Aged, 80 and over; Anti-Infective Agents; Antibiotic Prophylaxis; Cryptogenic Organizing Pneumonia; Dapsone; Female; Humans; Male; Methemoglobinemia; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Background- Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection seen in immunosuppressed patients, including solid-organ transplant recipients. Sulfamethoxazole/trimethoprim (SMX/TMP) has long been considered first-line therapy for PCP prophylaxis. Optimal dosing regimens in solid-organ transplant recipients have not been fully defined. Objective-To examine the tolerability of a 1-year, 3-times weekly, prophylactic regimen of a single-strength SMX/TMP tablet. Study Design-Single-center, retrospective cohort study. Setting-A tertiary-care medical center, including inpatient hospitalizations and outpatient transplant clinic visits. Patients-Adult patients who received a kidney transplant between December 1, 2010, and November 30, 2012, at Hartford Hospital. Patients receiving a concurrent extrarenal transplant were excluded. Patients' charts were reviewed for up to 1 year after transplant. Results-A total of 88 patients were included in the analysis. Sixty-seven patients finished a full year of SMX/TMP after transplant, 10 patients discontinued SMX/TMP less than 1 year after transplant, and 11 patients started taking atovaquone instead of SMX/TMP after transplant. Documented reasons for discontinuation included hyperkalemia, leukopenia, diarrhea, and simplification of medication regimen. Patients without a documented reason for discontinuation did not have any obvious anomalies in laboratory values that would account for the discontinuation. Patients who received atovaquone for PCP prophylaxis had higher rates of recurrent urinary tract infections than did patients who received SMX/TMP for prophylaxis (33% vs 7%, P = .02). A longer postoperative stay (median [interquartile range, IQR] 13 [8.25-26] days vs 7 [6-9.5] days, P = .02), higher rates of delayed graft function (50% vs 10%, P = .004), as well as higher serum creatinine levels on postoperative day 7 (6.25 [2.4-10.1] mg/dL vs 1.8 [1.2-4.2] mg/dL, P= .01), postoperative month 1 (1.9 [0.8] mg/dL vs 1.4 [0.5] mg/dL, P = .002), and postoperative month 12 (1.6 [0.5] mg/dL vs 1.3 [0.3] mg/dL, P = .04) were associated with early SMX/TMP discontinuation. Conclusion-A low-dose prophylactic SMX/TMP regimen of 1 single-strength tablet 3 times weekly is well tolerated. Discontinuation rates were lower than other rates reported for higher-dose regimens.

Topics: Adult; Anti-Bacterial Agents; Cohort Studies; Dose-Response Relationship, Drug; Female; Humans; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Patient Participation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is responsible for P. jirovecii pneumonia (PJP) in immunocompromised individuals, with a recent rise of cases noted in non-HIV patients. A middle-aged man presented with new-onset cough, fever, hypoxia and tachypnoea. He was on a tapering course of dexamethasone for amiodarone-induced thyrotoxicosis. He developed worsening airspace disease necessitating mechanical ventilation. Bronchoalveolar lavage (BAL) fluid was positive for P. jirovecii and he was managed with trimethoprim/sulfamethoxazole and pentamidine, but succumbed to cardiorespiratory arrest. One-third of PJP cases occur in non-HIV patients, and have a higher morbidity and mortality. Most immunocompromised patients typically exhibit PJP during a corticosteroid taper. The accurate dose, duration or frequency of steroid use in not well established. Diagnosis of PJP in this population is more challenging due to lower BAL yield with alternate modalities such as serum/BAL β-d-glucan and PCR enhancing the yield. Further studies are needed to highlight PJP prophylaxis in patients with steroid use.

Topics: Bronchoalveolar Lavage Fluid; Fatal Outcome; HIV Infections; Humans; Immunocompromised Host; Lung; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Female; Humans; Leukemia-Lymphoma, Adult T-Cell; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Receptors, CCR4; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) remains a concern after organ transplantation. In 2005, the University of Kentucky (UK) Transplant Center implemented a novel dosing regimen of weekly dapsone as an alternative for patients with contraindications or intolerability to trimethoprim-sulfamethoxazole (TMP-SMZ), which remains the drug of choice. The purpose of this study was to compare the efficacy of weekly dapsone with TMP-SMZ in preventing PCP post transplantation.. A single-center, cohort, retrospective review of kidney and liver transplant patients from January 2005 to December 2012 was conducted. Patients who were identified as dapsone cases were matched in a 1:1 ratio with TMP-SMZ controls based on type of transplant, age, primary diagnosis, and gender. The primary endpoint assessed was the diagnosis of PCP at 6 and 12 months post transplant.. A total of 158 patients were included in the study. No documented cases of PCP occurred in either study group at 6 or 12 months (P = 1.0). In dapsone patients 35 (44%) cases of breakthrough infection occurred, compared to 24 (30%) in the TMP-SMZ group (P = 0.07) within 12 months post transplant. In the dapsone group, 52 (65%) patients were hospitalized within 6 months post transplant compared to 36 (46%) patients in the TMP-SMZ group (P = 0.01). Similar results were seen in patients hospitalized within 12 months post transplant; 49% of patients were switched from TMP-SMZ to dapsone owing to renal dysfunction.. No documented cases of PCP occurred in either study group. Future studies are warranted to show the efficacy of weekly dapsone dosing compared to other PCP prophylaxis regimens.

Topics: Anti-Infective Agents; Cohort Studies; Dapsone; Humans; Immunosuppressive Agents; Kidney Transplantation; Liver Transplantation; Male; Opportunistic Infections; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Case We report the case of melphalan accumulation in an 80-year old female with multiple myeloma. Her initial health status was good except for a moderate chronic renal failure (estimated glomerular filtration rate: 31 ml/min) and anemia. Among other drugs, her usual treatment included trimethoprim/sulfamethoxazole and the patient received melphalan from day 1 to day 4 for multiple myeloma. On day 13, she was admitted in intensive care unit for acute renal failure and severe sepsis with pancytopenia. Usual treatments were stopped. Melphalan blood concentrations were 123.6 ng/ml on day 16 and 87.5 ng/ml on day 17 while cerebrospinal fluid concentration was 173.8 ng/ml on day 25. Patient recovered on day 30. Melphalan accumulation may be explained by substrate competition between sulfamethoxazole and melphalan in metabolism pathway and chronic renal failure. Conclusion close clinical and renal monitoring should be performed in patient receiving melphalan and sulfamethoxazole.

Topics: Acute Kidney Injury; Aged, 80 and over; Anti-Infective Agents; Antineoplastic Agents, Alkylating; Critical Care; Drug Interactions; Fatal Outcome; Female; Humans; Kidney Failure, Chronic; Melphalan; Multiple Myeloma; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Anticoagulants; Arterial Occlusive Diseases; Behcet Syndrome; Diagnostic Errors; Granulomatous Disease, Chronic; Humans; Immunocompromised Host; Lung; Male; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The HIV/AIDS health challenge continues to ravage many resource-constrained countries of the world. Approximately 75 % of all the global HIV/AIDS related deaths totaling 1.6 (1.4-1.9) million in 2012 occurred in sub-Saharan Africa, Uganda contributed 63,000 (52,000-81,000) to these deaths. Most of the morbidity and mortality associated with HIV/AIDS can be averted if individuals with HIV/AIDS have improved access to HIV care and treatment. The aim of this study therefore, was to explore the factors associated with access to HIV care services among HIV seropositive clients identified by a home based HIV counseling and testing program in Kumi district, eastern Uganda.. In a cross sectional study conducted in February 2009, we explored predictor variables: socio-demographics, health facility and community factors related to access to HIV care and treatment. The main outcome measure was reported receipt of cotrimoxazole for prophylaxis.. The majority [81.1 % (284/350)] of respondents received cotrimoxazole prophylaxis (indicating access to HIV care). The main factors associated with access to HIV care include; age 25-34 years (AOR = 5.1, 95 % CI: 1.5-17.1), male sex (AOR = 2.3, 95 % CI: 1.2-4.4), urban residence (AOR = 2.5, CI: 1.1-5.9) and lack of family support (AOR = 0.5, CI: 0.2-0.9).. There was relatively high access to HIV care and treatment services at health facilities for HIV positive clients referred from the Kumi home based HIV counseling and testing program. The factors associated with access to HIV care services include; age group, sex, residence and having a supportive family. Stakeholders involved in providing HIV care and treatment services in similar settings should therefore consider these socio-demographic variables as they formulate interventions to improve access to HIV care services.

Topics: Adolescent; Adult; Age Factors; AIDS Serodiagnosis; Anti-Infective Agents; Counseling; Cross-Sectional Studies; Family; Female; Health Services Accessibility; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Sex Factors; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

The combination of all-trans retinoic acid (ATRA) and primaquine (PMQ) has been shown to be effective for therapy of Pneumocystis pneumonia (PCP). Since a high concentration of ATRA has significant adverse effects, the possibility that vitamin D can be used to replace ATRA for PCP therapy was investigated. C57BL/6 mice were immunosuppressed by depleting CD4(+) cells and infected with Pneumocystis murina 1 week after initiation of immunosuppression. Three weeks after infection, the mice were treated orally for 3 weeks with vitamin D3 (VitD3) alone, PMQ alone, a combination of VitD3 and PMQ (VitD3-PMQ), or a combination of trimethoprim and sulfamethoxazole (TMP-SMX). Results showed that VitD3 (300 IU/kg/day) had a synergistic effect with PMQ (5 mg/kg/day) for therapy of PCP. Flow cytometric studies showed that this VitD3-PMQ combination recovered the CD11b(low) CD11c(high) alveolar macrophage population in mice with PCP as effectively as TMP-SMX. The VitD3-PMQ combination also reduced the massive infiltration of inflammatory cells into the lungs and the severity of lung damage. VitD3 was also shown to reduce the dose of TMP-SMX required for effective treatment of PCP. Taken together, results of this study suggest that a VitD3-PMQ combination can be used as an alternative therapy for PCP.

Topics: Albumins; Animals; Antifungal Agents; Calcium; CD11b Antigen; Cholecalciferol; Dietary Supplements; Drug Therapy, Combination; Female; L-Lactate Dehydrogenase; Lung; Macrophages, Alveolar; Mice, Inbred C57BL; Pneumocystis; Pneumonia, Pneumocystis; Primaquine; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To determine whether a simplified, 1-day/week regimen of trimethoprim/sulfamethoxazole is sufficient to prevent Pneumocystis (jirovecii [carinii]) pneumonia (PCP). Current recommended regimens for prophylaxis against PCP range from daily administration to 3 consecutive days per week dosing.. A prospective survey of the regimens adopted for the PCP prophylaxis in all patients treated for childhood cancer at pediatric hematology-oncology centers of the Associazione Italiana Ematologia Oncologia Pediatrica.. The 20 centers participating in the study reported a total of 2466 patients, including 1093 with solid tumor and 1373 with leukemia/lymphoma (or primary immunodeficiency; n = 2). Of these patients, 1371 (55.6%) received the 3-day/week prophylaxis regimen, 406 (16.5%) received the 2-day/week regimen, and 689 (27.9%), including 439 with leukemia/lymphoma, received the 1-day/week regimen. Overall, only 2 cases of PCP (0.08%) were reported, both in the 2-day/week group. By intention to treat, the cumulative incidence of PCP at 3 years was 0.09% overall (95% CI, 0.00-0.40%) and 0.51% for the 2-day/week group (95% CI, 0.10%-2.00%). Remarkably, both patients who failed had withdrawn from prophylaxis.. A single-day course of prophylaxis with trimethoprim/sulfamethoxazole may be sufficient to prevent PCP in children with cancer undergoing intensive chemotherapy regimens. This simplified strategy might have implications for the emerging need for PCP prophylaxis in other patients subjected to the increased use of biological and nonbiological agents that induce higher levels of immune suppression, such as those with rheumatic diseases.

Topics: Anti-Infective Agents; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Hematologic Neoplasms; Humans; Incidence; Italy; Pneumocystis carinii; Pneumonia, Pneumocystis; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim (TMP) is a commonly prescribed antibiotic with few adverse effects. However on rare occasions, TMP is associated with electrolyte disturbances. As seen in our three patients, TMP can be associated with symptomatic hyponatraemia which required hospitalization. In one of these patients, hyperkalaemia and type 4 renal tubular acidosis were also present. These electrolyte and acid-base disorders were corrected after discontinuation of TMP. A small number of patients with TMP-induced electrolyte imbalances have been reported in the English-language medical literature to date but mostly with the use of TMP in combination with sulfamethoxazole. In association with TMP use, hyperkalaemia has been more commonly reported than hyponatraemia. These changes in sodium and potassium balance are thought to be related to TMP inhibiting sodium ion influx via the epithelial sodium channel in the cortical collecting duct. The association between symptomatic hyponatraemia and TMP emphasizes the need to evaluate electrolytes in patients presenting with clinical change after commencing on this drug.

Topics: Aged; Alzheimer Disease; Anti-Infective Agents, Urinary; Female; Fever; Humans; Hyponatremia; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Saline Solution, Hypertonic; Sodium; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Water-Electrolyte Imbalance

Following a pneumocystis pneumonia (PCP) outbreak in our nephrology unit, all transplant patients were offered chemoprophylaxis with trimethoprim-sulphamethoxazole (TMP-SMX) as the first line agent. A high rate of complications was noted. We aimed to quantify TMP-SMX associated adverse events and evaluate its prophylactic benefit in their light. Potential risk factors for complications' development were also investigated.. This was an observational study of outcomes in transplant recipients commenced on TMP-SMX prophylaxis for 1year period. End-points were adverse events due to TMP-SMX, the additional medical burden resulting from these events, and PCP diagnosis.. 290 patients commenced on TMP-SMX. 110 (38%) developed complications with most common being rise in serum creatinine (Cr) (n = 63, 22%) followed by gastrointestinal symptoms (n = 15, 5%), and leucopenia (n = 5, 2%). PCP incidence fell from 19 cases in 19 months to 2 cases in 12 months. Baseline renal function (P = 0.019) was an independent predictors for developing rise in Cr with TMP-SMX.. Use of chemoprophylaxis is an effective strategy in dealing with a PCP outbreak but can lead to a high number of complications. Rises in serum Cr can cause significant concern and increase in the number of investigations.

Topics: Adult; Aged; Anti-Infective Agents; Chemoprevention; Creatinine; Female; Glomerular Filtration Rate; Humans; Kidney Transplantation; Male; Middle Aged; Pneumonia, Pneumocystis; Proportional Hazards Models; Trimethoprim, Sulfamethoxazole Drug Combination

This report presents the case of a 67-year-old woman affected by glioblastoma. After a few days of adjuvant therapy with temozolomide and prophylaxis with trimetrophin-sulfamethoxazolo to prevent Pneumocystis Jiroveci, she had progressive and rapid worsening of symptoms with weakness, dyspnea and orthopnea. She had peripheral edema and proximal hyposthenia of the lower limbs. Chest CT showed bilateral ground-glass opacities and laboratory exams revealed hypoxemia and hypocapnia, an initial reduction in platelet and white blood cells, and an elevation of LDH, AST, ALT, and active urinary sediment. Blood cultures, bronchoalveolar lavage (BAL) data and transbronchial biopsy showed no infections, and in particular no evidence of Pneumocystis Jiroveci pneumonia. Histological examination revealed a typical pattern of AIP. She was treated with broad-spectrum antibiotics and high-dose steroids. The symptoms worsened and respiratory failure required mechanical ventilation. The pneumonia was not responsive to medical or invasive care. She died after ten days of hospitalization. At present very little can be found in the literature about lung toxicity caused by temozolomide. This case can be added as a new report describing this risk. The combination therapy with temozolamide and trimetophin-sulfamethoxazolo could have a synergistic action inducing various forms of pulmonary toxicity. ESTABLISHED FACTS: Acute interstitial pneumonia is a common manifestation of lung toxicity caused by drugs. The clinical course is favorable with a good response to corticosteroids. NOVEL INSIGHT: This is the first fatal case of lung toxicity caused by Temozolomide. Clinicians must be aware that a combination therapy including trimetophin-sulfamethoxazolo could have a synergistic action in inducing pulmonary toxicity.

Topics: Aged; Antineoplastic Agents, Alkylating; Blood Gas Analysis; Brain Neoplasms; Bronchoalveolar Lavage Fluid; Dacarbazine; Electrocardiography; Fatal Outcome; Female; Glioblastoma; Humans; Lung; Lung Diseases, Interstitial; Physical Examination; Pneumocystis carinii; Pneumonia, Pneumocystis; Temozolomide; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is an important cause of hospitalization and mortality in HIV-infected children. However, the incidence of PCP has been underestimated due to poor sensitivity of diagnostic tests. The use of polymerase chain reaction (PCR) for pneumocystis has enabled more reliable diagnosis. This study describes the incidence, clinical features and outcome of PCP in South African children diagnosed using PCR.. A prospective study of children hospitalised in South Africa with suspected PCP was done from November 2006 to August 2008. Clinical, laboratory and radiological information were collected. Lower respiratory tract specimens were obtained for PCP immunofluorescence (IF), real- time PCR for pneumocystis, bacterial and mycobacterial culture. Nasopharyngeal aspirates were taken for immunofluorescence (IF), real-time PCR for pneumocystis and PCR for respiratory viruses. A blood specimen for bacterial culture and for cytomegalovirus PCR was taken. Children were followed for the duration of their hospitalisation and the outcome was recorded.. 202 children [median (interquartile range, IQR) age 3.2 (2.1- 4.6) months] were enrolled; 124 (61.4%) were HIV infected. PCP was identified in 109 (54%) children using PCR, compared to 43 (21%) using IF and Grocott staining (p < 0.0001). Most PCP cases (88, 81%) occurred in HIV-infected children. All 21 cases (19%) occurring in HIV- negative children had another risk factor for PCP. On logistic regression, predictive factors for PCP were HIV infection, lack of fever, high respiratory rate and low oxygen saturation whilst cotrimoxazole prophylaxis was protective (OR 0.24; 95% CI 0.1 to 0.5; p < 0.002). The case fatality of children with PCP was higher than those without PCP (32.1% versus 17.2%; relative risk 1.87; 95% confidence interval (CI) 1.11 - 3.15). Amongst HIV-infected children, a CD4 less than 15% was the only independent predictor of mortality.. The diagnostic yield for PCP is more than 2.5 times higher on PCR than other detection methods. PCP is a very common cause of severe hypoxic pneumonia and is associated with high mortality in HIV-infected African infants.

Topics: AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Bronchoalveolar Lavage Fluid; CD4 Lymphocyte Count; Cytomegalovirus Infections; Female; Fluorescent Antibody Technique; HIV Seronegativity; Humans; Incidence; Infant; Male; Nasopharynx; Oxygen; Pneumocystis; Pneumonia, Pneumocystis; Pneumonia, Viral; Predictive Value of Tests; Prednisone; Prospective Studies; Real-Time Polymerase Chain Reaction; Risk Factors; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents; Crohn Disease; Diarrhea; Drug Interactions; Female; Humans; Immunosuppressive Agents; Leucovorin; Methotrexate; Mucositis; Pneumonia, Pneumocystis; Prednisone; Stomatitis; Trimethoprim, Sulfamethoxazole Drug Combination

Anti-Pneumocystis prophylaxis is recommended for at least 6-12 months after solid organ transplantation, as most cases of Pneumocystis jirovecii pneumonia (PCP) occur during the first year post transplantation. Herein, we report 4 cases of late-onset PCP (>1 year post transplant). PCP appeared in a range of 50-68 months post transplant. Two cases had history of humoral rejection episodes treated with rituximab, and the other 2 had low CD4+ T-cell count (<200 cells/mm(3) ) at the time of diagnosis. All 4 patients survived. In conclusion, although the number of cases is low, we must be aware of the possibility of late-onset PCP in solid organ transplant patients. The role of previous use of rituximab or persistent CD4+ T-cell lymphopenia should be addressed in future studies.

Topics: Adult; Anti-Infective Agents; Female; Humans; Male; Middle Aged; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is one of the most prevalent opportunistic infections in patients undergoing immunosuppressive therapy. In this article, we discuss risk factors for PCP development in patients with rheumatoid arthritis (RA) during the course of biologic therapy and describe a prophylactic treatment for PCP with trimethoprim/sulfamethoxazole (TMP/SMX). We also evaluate the effectiveness and safety of the treatment.. We retrospectively analyzed 702 RA patients who received biologic therapy and compared the characteristics of patients with vs. without PCP to identify the risk factors for PCP. Accordingly, we analyzed 214 patients who received the TMP/SMX biologic agents as prophylaxis against PCP at the start of treatment to evaluate their effectiveness and safety.. We identified the following as risk factors for PCP: age at least 65 years (hazard ratio (HR) = 4.37, 95% confidence interval (CI) = 1.04 to 18.2), coexisting pulmonary disease (HR = 8.13, 95% CI = 1.63 to 40.0), and use of glucocorticoids (HR = 11.4, 95% CI = 1.38 to 90.9). We employed a protocol whereby patients with two or three risk factors for PCP would receive prophylactic treatment. In the study with 214 patients, there were no cases of PCP, and the incidence of PCP was reduced to 0.00 per 100 person-years compared with that before the procedure (0.93 per 100 person-years). There were no severe adverse events induced by the TMP/SMX treatment.. RA patients with two or three risk factors for PCP who are receiving biologic therapy can benefit from safe primary prophylaxis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Female; Humans; Immunocompromised Host; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

The Pneumocystis and Pneumocystosis: first meeting of experts from Latin-American and Portuguese-speaking countries was held in Lisbon, Portugal, on 24-26 October 2013. A total of 20 speakers from Latin America, Africa and Europe participated in the meeting. The epidemiological studies presented in this meeting begin to change the misconception that since the AIDS epidemic, Pneumocystis pneumonia (PcP) has become an infrequent disease, showing that today PcP remains a major opportunistic infection in HIV-infected patients in both developed and developing countries and an emerging problem in immunocompromised patients without HIV infection worldwide. PcP management remains a challenge. Right now, the combination of caspofungin and trimethoprim-sulfamethoxazole (TMP-SMX) is a promising therapeutic approach that needs to be assessed in controlled clinical trials.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Caspofungin; Developed Countries; Developing Countries; Echinocandins; Humans; Immunocompromised Host; Latin America; Lipopeptides; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Diagnosis, Differential; Dyspnea; Female; Fever; HIV Infections; HIV-1; Humans; Lung; Oxygen; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography; Sweating; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii (former carinii) pneumonia, is a life-threatening opportunistic infection occurring in immunocompromised hosts. The aim of this study was to investigate the predisposing factors, clinical features and outcome of Pneumocystis pneumonia (PCP) in HIV-negative patients. The medical records of 62 adult patients with PCP, hospitalized at the University Hospital of Heraklion, Crete, Greece during a 10-year period (2004-2013) were retrospectively reviewed. All patients were immunosuppressed prior to the development of PCP. Thirty one patients (50%) suffered malignant hematological disease, 16 (26%) solid tumor and 15 (24%) had chronic inflammatory disease. Only 17 (27%) had received long-term systemic corticosteroids. All had symptoms of pneumonia upon admission, while 12 (19%) were suffering respiratory failure. Twenty one (34%) had received trimethoprim/sulfamethoxazole (TMP-SMX) prophylaxis before the PCP onset. Eight patients (13%) were admitted to the ICU. Mortality attributable to PCP reached 29%. Mortality attributable to PCP was higher in patients with solid tumors. TMP-SMX prophylaxis failed in a significant portion of the present cohort. Hence, PCP should be included in the differential diagnosis in immunocompromised patients with symptoms from the respiratory tract even if TMP-SMX has been given as prophylaxis.

Topics: Aged; Causality; Female; Greece; HIV Infections; Humans; Immunocompromised Host; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

A 73-year-old woman with rheumatoid arthritis treated with methotrexate and prednisolone was admitted with dyspnea and ground-glass opacity on chest CT. We diagnosed her with Pneumocystis jirovecii pneumonia (PCP) based on a positive PCR analysis of Pneumocystis jirovecii and the presence of cysts in bronchoalveolar lavage fluid. The PaO2 was 74.7 Torr on room air, and treatment with sulfamethoxazole-trimethoprim only was initiated. The hypoxemia and ground-glass opacity increased on hospital day 3, and the administration of adjunctive steroid therapy resulted in an improvement in the patient's condition. Although patients with PCP with HIV infection and hypoxemia are often treated with adjunctive steroid therapy to prevent adverse immune reactions, the efficacy of additive steroid administration in case of non-HIV PCP has not been established.

Topics: Aged; Anti-Infective Agents; Arthritis, Rheumatoid; Chemotherapy, Adjuvant; Female; Glucocorticoids; Humans; Lung; Methotrexate; Methylprednisolone; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prednisolone; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/sulfamethoxazole (TMP/SMX) is considered first-line therapy for pneumocystis jiroveci pneumonia (PCP) in renal transplant patients. Alternatives have not been formally studied. Clindamycin-primaquine (C-P) is effective in HIV-associated PCP, but data in renal transplant patients are lacking.. Retrospective cohort study of 57 consecutive renal transplant patients who developed PCP and were treated with C-P (n = 23) or TMP/SMX (n = 34).. A non-significantly higher failure rate was observed in patients on C-P due to lack of efficacy (30.4 versus 20.6%, p = 0.545). The difference was more pronounced in severe PCP (60 versus 37.5%, p = 0.611) and a significantly lower efficacy of C-P was seen when used as salvage therapy. The two patients who had received C-P after not responding to TMP/SMX failed this regimen, but all seven patients who had failed initial treatment with C-P and had been switched to TMP/SMX were cured (p = 0.028). No treatment-limiting adverse reactions were reported for patients on C-P while six patients (17.6%) on TMP/SMX developed possibly related treatment-limiting toxicity (p = 0.071). However, in only two patients adverse events were definitely related to TMP/SMX (5.9%).. Clindamycin-primaquine appears to be safe and well tolerated for treating PCP in renal transplant patients but is probably less effective than TMP/SMX, the standard regimen. However, our data indicates that C-P represents an acceptable alternative for patients with contraindications or treatment emergent toxicities during TMP/SMX use. Notably, TMP/SMX was also acceptably tolerated in most patients. TMP/SMX remains an effective salvage regimen in case of C-P failure.

Topics: Adult; Aged; Antifungal Agents; Clindamycin; Cohort Studies; Female; Humans; Kidney Transplantation; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Primaquine; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145-0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity.

Topics: Adult; Aged; Aged, 80 and over; Anti-HIV Agents; Anti-Infective Agents; Arylamine N-Acetyltransferase; Chemical and Drug Induced Liver Injury; Drug Interactions; Female; Fluconazole; Gene Expression; HIV; HIV Infections; Humans; Isoenzymes; Liver; Male; Middle Aged; Multivariate Analysis; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymorphism, Single Nucleotide; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/sulfamethoxazole (TMP/SMX) is the recommended first-line treatment for human immunodeficiency virus (HIV)-infected patients with Pneumocystis jirovecii pneumonia (PJP).However, in June 2010, the lone manufacturer of intravenous (IV) TMP/SMX in the United States stopped production of this medication. . To (a) evaluate the impact of the national IV TMP/SMX shortage on PJP treatment outcomes between 2 groups of HIV-infected patients-those treated before the shortage and those after the shortage-and (b) compare the length of hospital stay (LOS) and PJP treatment used before and after the shortage.. A retrospective, quasi-experimental study examining 2 groups of HIV-infected adult patients with PJP was performed at an academic medical center from September 1, 2008, to June 30, 2012. Patients treated when IV TMP/SMX was available, or preshortage (PRE), were compared with patients treated when IV TMP/SMX was not available, or postshortage (POST).PRE included patients treated between September 1, 2008, and May 30, 2010, and POST included patients treated between June 1, 2010, and June 30, 2012.  . Thirty-six patients were included in the study, 18 in each group. Treatment failure, the primary outcome, included mortality or worsening clinical status (WCS) after at least 5 days of therapy. Three patients in PRE (16.7%) and 6 patients in POST (33.3%) experienced treatment failure (P = 0.248). No patients in PRE and 3 patients in POST (16.7%) experienced WCS (P = 0.035). Three patients in each group expired.In POST, 5 of the 6 treatment failures (83.3%) occurred during the first 6 months of the shortage. Median (interquartile range) LOS was 11 days (7-17) in PRE and 14 days (5-22) in POST (P = 0.800).In PRE, 7 patients (38.9%) were initiated on oral PJP treatment compared with 13 (72.2%) in POST (P = 0.042). . The national shortage of IV TMP/SMX may have led to an immediate but temporary negative impact on treatment outcomes among HIV-infected patients with PJP at an academic medical center.Pharmacist collaboration with physicians may have helped mitigate the impact of this drug shortage on patient outcomes.  

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Therapy, Combination; Female; HIV Infections; Humans; Infusions, Intravenous; Male; Medical Records; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; United States

To assess the results of diagnosing and treating Pneumocystis pneumonia (PP) in patients with Hodgkin lymphoma (HL) over 15 years.. In 1999 to 2013, PP occurred in 22 (3%) of 741 HL patients receiving programmed polychemotherapy (PCT). The male/female ratio was 1:1.1; median age was 32 (18-65) years. Advanced stages (IIB-IV) of the disease were seen in 82% of the patients. The diagnosis of PP was established when Pneumocystis (more than 5 cysts in the specimen) was detected in the lavage fluid by indirect immunofluorescence assay.. PP developed after 4 or more cycles of PCT. Along with Pneumocystis, all the cases were found to have additional pathogens: herpes virus in 72% and bacteria and fungi in 33%. All the patients received combined antimicrobial therapy using high doses of intravenous trimethoprim-sulfamethoxazole. Ten (45%) patients required mechanical ventilation (MV). The total mortality in PP was 32% (7 patients died); moreover, none of the patients without MV died whereas the mortality among those who had MV was 70% (7 of the 10 patients died). High death rates (80%) were noted among the patients with recurrent and resistant HL.. PP should be prevented with trimethoprim-sulfamethoxazole in patients with LH during PCT. If respiratory failure and X-ray signs of interstitial pneumonia appear, there is a need for fibrobronchoscopy with bronchoalveolar lavage and comprehensive microbiological testing of lavage fluid.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bronchoalveolar Lavage Fluid; Female; Fluorescent Antibody Technique, Indirect; Hodgkin Disease; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Respiration, Artificial; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

A 76-year-old female with advanced renal cell carcinoma had been treated with everolimus for 3 months. She visited our hospital because of a cough and fever lasting a few days. Chest X-rays showed bilateral infiltrative shadows, and a chest computed tomography scan showed homogeneous ground-glass opacities with mosaic patterns, especially in the apical region. The laboratory results revealed a decreased white blood cell count with lymphocytopenia and high levels of lactate dehydrogenase, C-reactive protein and KL-6. Pneumonitis was suspected and, therefore, everolimus therapy was interrupted. At that time, the pneumonitis was thought to be drug-induced interstitial lung disease. However, it was not possible to rule out pneumocystis pneumonia, because the patient was immunocompromised and the computed tomography findings suggested the possibility of pneumocystis pneumonia. The pneumonitis progressed rapidly and the patient developed respiratory failure, so we performed bronchoalveolar lavage to make a definitive diagnosis, and simultaneously started treatment with prednisolone and trimethoprim-sulfamethoxazole to cover both interstitial lung disease and pneumocystis pneumonia. A polymerase chain reaction assay of the bronchoalveolar lavage fluid was positive for Pneumocystis carinii DNA, and the serum level of β-d-glucan was significantly elevated. Thus, the patient was diagnosed with pneumocystis pneumonia, which was cured by the treatment. Interstitial lung disease is a major adverse drug reaction associated with everolimus, and interstitial lung disease is the first condition suspected when a patient presents with pneumonitis during everolimus therapy. Pneumocystis pneumonia associated with everolimus therapy is rare, but our experience suggests that pneumocystis pneumonia should be considered as a differential diagnosis when pneumonitis is encountered in patients receiving everolimus therapy.

Topics: Aged; Anti-Infective Agents; Antineoplastic Agents; Bronchoalveolar Lavage; Carcinoma, Renal Cell; Diagnosis, Differential; Drug Administration Schedule; Everolimus; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Neoplasms; Lung Diseases, Interstitial; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Respiratory Insufficiency; Sirolimus; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

More than 90% of cases of pneumocystis pneumonia (PCP) in adults occur in patients with chronic HIV infection with CD4 counts lower than 200 cells/ml. Even though primary HIV infection can cause transient profound CD4 lymphocytopenia, PCP is rarely reported during primary HIV infection. We report a case of a 26-year-old man who was diagnosed with PCP in the setting of primary HIV infection. He was successfully treated with a 21-day course of oral co-trimoxazole.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A man in his late 50s with a history of membranoproliferative glomerulonephritis presented with fever and mild dyspnoea. He was HIV-negative and had been on corticosteroids as immunosuppression for 6 months prior to tapering them off 1 week before presentation. He was not taking prophylaxis for Pneumocystis jirovecii pneumonia. After unsuccessful treatment for community-acquired pneumonia, his condition worsened and he required intubation and mechanical ventilation. Full respiratory workup including bronchoscopy revealed P jirovecii as a source for the patient's infection. He was treated successfully with a 21-day course of trimethoprim-sulfamethoxazole  and eventually weaned off the ventilator. He has had no complications to date. In our review of this case and the existing literature, we believe that proper utilisation of prophylaxis for pneumocystis pneumonia may have prevented our patient's transfer to intensive care unit. In our article, we discuss this issue and explore current evidence for prophylaxis.

Topics: Anti-Infective Agents; Antibiotic Prophylaxis; Bronchoscopy; Diagnosis, Differential; Humans; Intubation, Intratracheal; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Respiration, Artificial; Trimethoprim, Sulfamethoxazole Drug Combination

  Japanese patients with normal renal function were retrospectively analyzed to characterize increases in serum creatinine (SCr) observed following the use of a sulfamethoxazole-trimethoprim (SMX-TMP) combination product and identify factors affecting these increases. In the patients studied (n=49), an individual comparison was conducted for the three factors of age group [≤74 years (n=21) vs. ≥75 years (n=28)], sex [male (n=24) vs. female (n=25)], and total dose throughout the treatment period [≤7 g (n=24) vs. ≥8 g (n=25)] to determine the extent of SCr increase following SMX-TMP combination product use. SCr increased significantly following SMX-TMP combination product use in patients ≤74 years of age and ≥75 years of age, in both males and females, and in patients with a total dose of ≥8 g (8 to 96 g) (p<0.05). Multivariate logistic regression analysis was used to determine the independence of these factors. Total dose was identified as an independent factor and had an odds ratio of 6.571 [95% confidence interval=1.735-24.882, p=0.006]. Post-treatment percent increases in SCr were compared using pre-treatment levels as the baseline. The group with a total dose of ≥8 g (mean 29.8 g) had a significant SCr increase of 18.4% (p=0.002), while the increase in the ≤7 g (mean 5.3 g) group was only 4.5%. The data showed that SCr increased by about 20% when the total dose taken over the treatment period was around 30 g (about 2.4 g as TMP) and indicated that total dose contributes more than age and sex to the post-treatment increase in SCr.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Anti-Inflammatory Agents, Non-Steroidal; Asian People; Creatinine; Diuretics; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Kidney; Male; Middle Aged; Monitoring, Physiologic; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Sex Factors; Trimethoprim, Sulfamethoxazole Drug Combination

The introduction of sulfa drugs for the chemotherapy of bacterial infections in 1935 revolutionized medicine. Although their mechanism of action is understood, the molecular bases for most of their side effects remain obscure. Here, we report that sulfamethoxazole and other sulfa drugs interfere with tetrahydrobiopterin biosynthesis through inhibition of sepiapterin reductase. Crystal structures of sepiapterin reductase with bound sulfa drugs reveal how structurally diverse sulfa drugs achieve specific inhibition of the enzyme. The effect of sulfa drugs on tetrahydrobiopterin-dependent neurotransmitter biosynthesis in cell-based assays provides a rationale for some of their central nervous system-related side effects, particularly in high-dose sulfamethoxazole therapy of Pneumocystis pneumonia. Our findings reveal an unexpected aspect of the pharmacology of sulfa drugs and might translate into their improved medical use.

Topics: 5-Hydroxytryptophan; Adult; Alcohol Oxidoreductases; Anti-Infective Agents; Biopterins; Cell Line; Central Nervous System; Crystallography, X-Ray; Fibroblasts; Humans; Levodopa; NADP; Nausea; Pneumonia, Pneumocystis; Protein Conformation; Structure-Activity Relationship; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination; Vomiting

Pneumocystis jirovecii pneumonia (PCP) represents an important cause of morbidity and mortality in kidney transplant recipients. In recent years an increasing number of PCP outbreaks have been reported worldwide.. We performed a retrospective study including the demographic, clinical, laboratory, and therapeutic parameters of all renal transplant recipients with PCP in Slovenia during the period from January 1, 2006, to December 31, 2011.. At the end of the 2011, 13/601 (2.2%) kidney transplant recipients followed in our center experienced PCP. The median time from transplantation to development of disease was 17 months (range, 3-148). Three recipients had PCP during the first year after transplantation because of early trimethoprim and sulfamethoxazole (TMP-SMX) discontinuation; in 3, it was related to acute graft rejection treatment; and in 6, to cytomegalovirus (CMV) infection. Pneumocystis jirovecii was microbiologically confirmed in 10 recipients. In 10 of 13 patients serum concentrations of lactic acid dehydrogenase (LDH) were increased. In addition, serum concentrations of beta-d-glucan was determined in 9 cases was elevated in each one.. The incidence of PCP was low, most probably owing to prolonged (12 months) TMP-SMX prophylaxis. Premature TMP-SMX discontinuation in the first year after transplantation, treatment of graft rejection and CMV infection seemed to be risk factors for PCP. Elevated serum beta-d-glucan concentration was a better noninvasive indicator of P jirovecii infection than elevated serum LDH concentration. In cases with no microbiological conformation, beta-d-glucan and LDH concentrations were helpful to establish the diagnosis of PCP for early treatment.

Topics: Adult; Aged; Female; Graft Rejection; Humans; Incidence; Kidney Transplantation; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Slovenia; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PcP) is a well-recognized major opportunistic infection in HIV-infected patients. During the 1980s, the HIV pandemic turned PcP into a major worldwide medical and public health problem. With the introduction of Pneumocystis chemoprophylaxis and the development of highly active antiretroviral therapy (ART) for the treatment of HIV infection, there has been a decrease in PcP incidence in developed countries. However, the prevalence of AIDS-related PcP in developing countries remains high because a lot of people do not have access to ART or ignore their HIV infection status. This article discusses the information available about PcP among Latin American countries where there is a great regional heterogeneity in the prevalence of HIV infection and in ART coverage, as well as in the observed frequencies of PcP that range from 5.9 to 55% in this area.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antifungal Agents; Antiretroviral Therapy, Highly Active; Coinfection; Developing Countries; Female; HIV; Humans; Latin America; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Prevalence; Public Health; Trimethoprim, Sulfamethoxazole Drug Combination

Primary HIV infection can occur in 40-90% of individuals recently infected with HIV. Variable symptoms usually suggestive of a flu-like illness as well as high-level HIV viraemia and steep decline in CD4 cell count are often noted. We report a case of a previously healthy homosexual man who presented with symptoms suspicious of primary HIV infection as well as non-productive cough associated with chest CT finding of diffuse ground glass appearance in lungs. Recent HIV seroconversion was confirmed. Diagnosis of Pneumocystis jirovecii pneumonia was made on transbronchial lung biopsy. The symptoms improved rapidly after initiation of treatment with trimethoprim-sulfamethoxazole. It is important to recognise that although Pneumocystis pneumonia is generally seen in the setting of AIDS, it can occasionally also occur during primary HIV infection.

Topics: AIDS-Related Opportunistic Infections; Diagnosis, Differential; HIV Infections; HIV Seropositivity; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

We herein report a case of methemoglobinemia induced by trimethoprim-sulfamethoxazole (TMP/SMX). A 41-year-old woman with systemic lupus erythematosus (SLE) received TMP/SMX for prophylaxis of pneumocystis pneumonia (PCP) on the 7th day of hospitalization. She suddenly developed dyspnea and cyanosis on the 9th day of hospitalization. The level of oxygen saturation (SaO2) decreased, and the concentration of methemoglobin (MetHb) in the blood was elevated. We diagnosed the patient with methemoglobinemia induced by TMP/SMX. Methemoglobinemia should be considered in cases of sudden dyspnea following TMP/SMX administration.

Topics: Adult; Anti-Infective Agents; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Methemoglobinemia; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Withholding Treatment

Pneumocystis pneumonia (PcP) is a major cause of mortality and morbidity in immunocompromised patients. There are limited alternative therapeutic choices to trimethoprim-sulfamethoxazole (TMP-SMX) which is the standard first line therapy/prophylaxis for PcP. The efficacy of low doses of caspofungin and caspofungin in association with TMP-SMX standard-prophylactic dose was evaluated in an experimental model of Pneumocystis. Susceptibility of Pneumocystis spp. to low doses of caspofungin and caspofungin/TMP-SMX was evaluated in Balb/c immunosuppressed mice, infected intranasally with P. murina. Caspofungin was administered once daily at 0.1 mg/kg, 0.05 mg/kg, and 0.001 mg/kg and TMP-SMX was administered by oral gavage (12.25 mg/62.5 mg/day), for 21 days. Efficacy was calculated based on the reduction in organism burden determined through quantitative fluorescent-based real-time PCR (qPCR). Serum β-1,3-D-glucan was measured as an additional marker of infection. The present data showed that caspofungin demonstrated anti-Pneumomocystis effect. However, the doses administrated were too low to achieve Pneumocystis eradication, which suggests that echinocandin treatment should not be administrated as mono-therapy. After 21 days of treatment, P. murina was not detected in the lungs of mice with either TMP-SMX or caspofungin/TMP-SMX. The results showed that, even at the lowest concentrations tested, the efficacy of caspofungin in association with TMP-SMX was higher than the efficacy of either drug used alone. The administration of caspofungin/TMP-SMX was at least 1.4 times more effective against P. murina infection than TMP-SMX used alone. The most promising result was achieved with the combination of caspofungin 0.05 mg/kg/day with TMP-SMX 12.5 mg-62.5 mg/day, which reduced the parasite burden to undetectable levels immediately at the 14(th) day of treatment, showing a highly marked anti-Pneumomocystis effect. These data suggest that the administration of low doses of caspofungin in combination with low doses of TMP-SMX may provide an improved treatment protocol for Pneumocystis infection clearance.

Topics: Animals; Caspofungin; Disease Models, Animal; Drug Combinations; Echinocandins; Lipopeptides; Male; Mice; Mice, Inbred BALB C; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pulmonary alveolar proteinosis (PAP) is a rare disease with worldwide distribution and an estimated incidence of 0.36 cases per million. We report a case of a PAP coexisting with Pneumocystis jiroveci pneumonia and Mycobacterium tuberculosis infection. The patient was treated with serial lobar lung lavages, GM-CSF, cotrimoxazole, and antituberculosis drugs. His PaO2 on room air improved from 45.7 to 63.8 torr and pulmonary functions normalized (FVC 81.2%, FEV1 95.3%, FEV1/FVC 91.8). A high-resolution computed tomography scan of the thorax showed clearing of both lower lobes. Whole-lung lavage is used in the treatment of PAP, but it may worsen the hypoxemia and lead to hemodynamic instability during the procedure. To the best of our knowledge, there are no reports of bronchoscopic serial lobar lung lavages in cases of PAP performed in India. This method can be performed in bronchoscopic suites having general anesthesia facilities without the requirement of special gadgets.

Topics: Adult; Anti-Infective Agents; Bronchoalveolar Lavage; Bronchoscopy; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hypoxia; India; Male; Oxygen; Periodic Acid-Schiff Reaction; Pneumonia, Pneumocystis; Pulmonary Alveolar Proteinosis; Respiration, Artificial; Respiratory Function Tests; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Pneumocystitis may cause fatal pneumonia in premature, seriously ill infants at intensive care units. The present study evaluated the routine treatment applied at Sohag pediatrics department for neonatal and infantile pneumonia (in NICU & PICU) on PCP and to compare between the stained slides and real time-PCR in diagnosing Pneumocystis jirovecii. Sucked sputum from 21 pneumonic infants was collected, some for Giemsa stain and microscopic examination and the rest for PCR. The same procedure was done after regression of the symptoms and before release from the units. Serum samples were also collected on admission and discharge for CRP readings which was also used as an indicative of the healing process. Out of 21 pneumonic neonates and infants examined, 12 (57.1%) showed P. jirovecii in sputum samples with a significant difference between both groups (p=0.2). 10 of them (83.3%) became negative for P. jirovecii under the routine regimen of treatment. Also 2 cases were infected with microspora, both improved at the end of treatment. While real time PCR was negative in all cases pre and post treatment. CRP levels regressed after treatment in all cases except 2 as one showed post treatment P. jirovecii in the sputum.

Topics: Animals; Drug Therapy, Combination; Humans; Infant; Infant, Newborn; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Real-Time Polymerase Chain Reaction; Trimethoprim, Sulfamethoxazole Drug Combination

To identify the risk factors which will indicate the Pneumocystis carinii (Pc) infection in children with systemic lupus erythematosus (SLE) and investigate the clinical features and to elevate the level to find out the high-risk patients and make early diagnosis and treatment.. The characteristics, clinical features, laboratory examinations, treatment and prognosis of Pneumocystis carinii pneumonia (PCP) in children with SLE under 18 years of age treated in our hospital between January 2000 and January 2013 were prospectively reviewed. A comparison was made with the 26 cases of SLE children without PCP who were matched for gender, age and course, and a literature review was made.. (1) Five cases were enrolled, 3 were male and 2 female. Their age range was 13-17 (14.0 ± 1.6) years. All the children had kidney involvement. The courses were from 3 months to 4.5 years. All patients were receiving daily glucocorticoid therapy and immunosuppressive drugs before the diagnosis of PCP.Four patients were in the inactive phase of SLE (SLEDAI 2-4 points), and the fifth case was in active phase (SLEDAI 8, low complement 2 points, anti-dsDNA antibody positive 2 points, urine-protein 4 points). (2) Besides the clinical manifestations of SLE, most patients had progressive dyspnea, fever and dry cough at onset of PCP. Two children accepted mechanical ventilation because of respiratory failure. The mean duration of the symptoms to diagnosis was 10-30 (17.6 ± 7.8) days. Lactose dehydrogenase (LDH) was elevated more or less, median was (700 ± 263) U/L. Lymphocyte count were (0.3-1.4)×10(9)/L (median 0.5×10(9)/L), and three children had CD4 T lymphocyte count <0.3×10(9)/L. Arterial blood gas analyses showed severe hypoxemia. Chest radiographs showed in all cases diffuse interstitial infiltration. Pc was positive in the sputum. All patients were treated with trimethoprim-sulfamethoxazole and corticosteroids.. When SLE children are treated with corticosteroids and immunosuppressive drugs, low lymphocyte count is the risk factor for Pc infection.It is essential to monitor lymphocyte count.We should pay more attention to fever, dry cough and hypoxemia. Chest radiologic examination may help diagnose the PCP in SLE children.It may be helpful for SLE children whose CD4T lymphocyte was below 0.3×10(9)/L to take trimethoprim-sulfamethoxazole for PCP prophylaxis.

Topics: Adolescent; Anti-Infective Agents; Case-Control Studies; Child; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Kidney Diseases; Lung; Lupus Erythematosus, Systemic; Lymphocyte Count; Male; Opportunistic Infections; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulphamethoxazole (TMP-STX), an agent used for prophylaxis against pneumocystis pneumonia (PCP) in immunocompromised hosts, causes serious adverse effects (AEs) in some patients. The objective of this study was to identify the risk factors for AEs caused by TMP-STX in connective tissue disease (CTD) patients and to describe the clinical features of the AEs.. The medical records of 539 patients (CTDs 312, pulmonary diseases 227) receiving TMP-STX for prophylaxis against PCP were reviewed retrospectively. Patients with human immunodeficiency virus were excluded. Univariate and multivariate analyses were conducted to identify the risk factors.. Adverse events caused by TMP-STX occurred in 22 of 312 (7.05 %) CTD patients, while only six of 227 (2.64 %) pulmonary disease patients developed AEs. The incidence of AEs was significantly higher in systemic lupus erythematosus (SLE) (11.0 %) and mixed connective tissue disease (MCTD) (33.3 %) patients than in other CTD patients. AEs occurred in 25 % of patients with anti-RNP antibody. Univariate analysis revealed that SLE, MCTD, and anti-RNP antibody were risk factors for AEs in CTD patients. Further multivariate analyses demonstrated that only anti-RNP antibody positivity was a risk factor for AEs. Systemic inflammation, including fever, was a characteristic manifestation of the AEs in CTD patients, particularly those with anti-RNP antibody.. Positivity for anti-RNP antibody is a risk factor for AEs caused by TMP-STX in CTD patients. Systemic inflammation, including fever, might be a characteristic feature of the AEs in CTD patients, particularly those with anti-RNP antibody.

Topics: Aged; Anti-Infective Agents; Antibiotic Prophylaxis; Antibodies, Antinuclear; Connective Tissue Diseases; Female; Humans; Lung Diseases; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Ribonucleoproteins; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

The case is presented of a 38 year-old patient who was admitted in the Emergency Department due to a severe acute respiratory failure and who was transferred to the Critical Care Unit with a suspected initial diagnosis of community acquired pneumonia caused by an atypical microorganism, which was complicated with an acute respiratory distress syndrome. This was able to be treated with non-invasive mechanical ventilation. At 48 hours after admission, the growth of Gram negative bacilli in the blood culture was reported, which was subsequently identified as Salmonella enteritidis. This information, along with the lymphopenia suffered by the patient, suggested an immunodepressed state, thus serological tests were performed which showed positive for HIV. Antibiotic treatment was started based on the microbiological findings, with a favourable clinical outcome for the patient.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Bacteremia; Bronchoalveolar Lavage Fluid; Ceftriaxone; Cocaine-Related Disorders; Community-Acquired Infections; Diagnosis, Differential; Female; Humans; Lymphopenia; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Respiratory Distress Syndrome; Salmonella enteritidis; Salmonella Infections; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the safety and efficacy of a dose-escalation regimen of trimethoprim-sulfamethoxazole (TMP/SMX) for prophylaxis against Pneumocystis jiroveci pneumonia (PCP) in rheumatic diseases.. Data from 41 patients, who received glucocorticoids with or without immunosuppressive agents and prophylactic use of TMP/SMX, were retrospectively analyzed. Thirteen patients were started on a daily dose of 10% of single-strength (SS) TMP/SMX, which was increased gradually (dose-escalation group), while 28 patients were started on 1 SS tablet daily (routine group).. In the dose-escalation group, the retention rate was 100% at 6 months. In the routine group, 5 patients discontinued TMP/SMX; the retention rate was 82.1%. Moreover, the retention rate when taking a daily dose of 50% or more of SS TMP/SMX, or 1 SS tablet thrice-weekly, was significantly higher in the dose-escalation group (100 versus 71.4%, P = 0.032). No PCP was observed in the dose-escalation group; however, 1 patient in the routine group, who had discontinued TMP/SMX, developed PCP. The rate of adverse effects was less, although nonsignificant, in the dose-escalation group (30.8 versus 46.4%, P = 0.344).. In rheumatic diseases, a dose-escalation regimen of TMP/SMX resulted in a higher retention rate and was safer than the routine regimen.

Topics: Adult; Aged; Aged, 80 and over; Antibiotic Prophylaxis; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Rheumatic Diseases; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Rituximab, an anti-CD20 antibody that targets B cells, is a promising agent against steroid-dependent and steroid-resistant nephrotic syndrome in children.. We report a 3-year-old boy who presented with atypical Pneumocystis jiroveci pneumonia (PCP) following administration of rituximab for refractory nephrotic syndrome. He had received cyclosporine and daily prednisolone for over 1 year. Following rituximab therapy, a hazy shadow was observed on his chest X-ray. Chest-computed tomography revealed multiple nodular lesions in bilateral lungs, although his clinical symptoms were subtle. PCR analysis demonstrated the presence of Pneumocystis DNA in his bronchoalveolar lavage. Lung wedge resection of the nodular lesion exhibited granulomas containing a few cysts of P. jiroveci that primarily consisted of T cells and histiocytes and lacked B cells. A deficiency of B cells following rituximab treatment suggests a dramatic effect on the immune response and, therefore, could result in granulomatous PCP. Nodular granulomatous lesions of PCP comprise an emerging concept previously reported in adults with hematological disease, bone marrow transplant, or treatment with rituximab. We report the first pediatric case of nodular PCP. Granulomatous PCP can be life-threatening. Moreover, bronchoalveolar lavage often fails to demonstrate the presence of P. jiroveci DNA. Wedge biopsy is warranted for definitive diagnosis. Our patient fully recovered with sulfamethoxazole/trimethoprim treatment because of early detection.. The indication of rituximab for refractory nephrotic syndrome has increased recently. Therefore, recognition of the risk of atypical PCP is important. Our findings suggest that PCP prophylaxis should be considered following rituximab therapy.

Topics: Anti-Infective Agents; Antibodies, Monoclonal, Murine-Derived; Child, Preschool; Granuloma; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Nephrotic Syndrome; Pneumocystis carinii; Pneumonia, Pneumocystis; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination

A 47-year-old, non-smoking woman was admitted to the National Tuberculosis and Lung Diseases Research Institute for diagnosis of progressive exertional dyspnoea and numerous small thin-walled, air-filled cysts equally distributed throughout both lungs revealed in HRCT (high resolution computed tomography) examination. Histological assessment of specimens obtained by open lung biopsy revealed proliferation of immature smooth muscle, showing the expression of the antigen HMB45. On this basis, diagnosis of lymphangioleiomyomatosis was established. The disease caused essential ventilation damage of the lungs (FEV1 1.34 L; 39.71% pred, VC 4.02 L; 94.96% pred, FEV1/ /VC 0.33-4 1.81% pred, DLCO 3.65 mmol/min/Kpa 38.35% pred).During the observation, despite the lack of immunological disorders, the patient developed Pneumocystis jiroveci pneumonia (PCP) that was treated with trimethoprimsulfamethoxazole. Lymphangioleiomyomatosis is a rare disease which results from a defect of TSC genes. The disease is not related to immunological defects or disorders. However, the considerable cystic destruction of the lungs can predispose the patient to opportunistic infections such as the one in the presented case.

Topics: Anti-Infective Agents; Female; Humans; Lung Neoplasms; Lymphangioleiomyomatosis; Middle Aged; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations have been associated with failure of sulfa prophylaxis; their effect on the outcome of patients with P. jirovecii pneumonia (PCP) remains controversial. P. jirovecii DHPS polymorphisms and genotypes were identified in 112 cases of PCP in 110 HIV-infected patients by using PCR single-strand conformation polymorphism. Of the 110 patients observed, 21 died; 18 of those deaths were attributed to PCP. Thirty-three percent of the PCP cases involved a P. jirovecii strain that had 1 or both DHPS mutations. The presence or absence of DHPS mutations had no effect on the PCP mortality rate within 1 month, whereas P.jirovecii type 7 and mechanical ventilation at PCP diagnosis were associated with an increased risk of death caused by PCP. Mechanical ventilation at PCP diagnosis was also associated with an increased risk of sulfa treatment failure at 5 days.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child, Preschool; Coinfection; Dihydropteroate Synthase; Drug Resistance, Fungal; Female; France; Fungal Proteins; HIV Infections; Humans; Infant; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Respiration, Artificial; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-HIV Agents; Anti-Infective Agents; CD4 Lymphocyte Count; Chemoprevention; Community-Acquired Infections; Cough; Dyspnea; Fatal Outcome; HIV Infections; Humans; Lymphatic Diseases; Lymphoma, Non-Hodgkin; Male; Medication Adherence; Pancytopenia; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography; Sarcoma, Kaposi; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PcP) develops in immunocompromised patients. Alveolar macrophages play a key role in the recognition, phagocytosis, and degradation of Pneumocystis, but their number is decreased in PcP. Our study of various inflammatory components during PcP found that myeloid-derived suppressor cells (MDSCs) accumulate in the lungs of mice and rats with Pneumocystis pneumonia (PcP). We hypothesized that treatment with all-trans retinoic acid (ATRA), a metabolite of vitamin A, may effectively control Pneumocystis (Pc) infection by inducing MDSCs to differentiate to AMs. In rodent models of PcP, we found that 5 weeks of ATRA treatment reduced the number of MDSCs in the lungs and increased the number of AMs which cleared Pc infection. We also found that ATRA in combination with primaquine was as effective as the combination of trimethoprim and sulfamethaxazole for treatment of PcP and completely eliminated MDSCs and Pc organisms in the lungs in two weeks. No relapse of PcP was seen after three weeks of the ATRA-primaquine combination treatment. Prolonged survival of Pc-infected animals was also achieved by this regimen. This is the very first successful development of a therapeutic regimen for PcP that combines an immune modulator with an antibiotic, enabling the hosts to effectively defend the infection. Results of our study may serve as a model for development of novel therapies for other infections with MDSC accumulation.

Topics: Animals; Cell Differentiation; Drug Synergism; Drug Therapy, Combination; Female; Humans; Immunocompromised Host; Lung; Macrophages, Alveolar; Mice; Mice, Inbred BALB C; Pneumocystis; Pneumonia, Pneumocystis; Primaquine; Rats; Rats, Sprague-Dawley; Survival Analysis; Tretinoin; Trimethoprim, Sulfamethoxazole Drug Combination

We communicate the diagnosis by microscopy of a pulmonary coinfection produced by Cryptococcus neoformans and Pneumocystis jiroveci, from a respiratory secretion obtained by bronchoalveolar lavage of an AIDS patient. Our review of literature identified this coinfection as unusual presentation. Opportunistic infections associated with HIV infection are increasingly recognized. It may occur at an early stage of HIV-infection. Whereas concurrent opportunistic infections may occur, coexisting Pneumocystis jiroveci pneumonia (PCP) and disseminated cryptococcosis with cryptococcal pneumonia is uncommon. The lungs of individuals infected with HIV are often affected by opportunistic infections and tumours and over two-thirds of patients have at least one respiratory episode during the course of their disease. Pneumonia is the leading HIV-associated infection. We present the case of a man who presented dual Pneumocystis jiroveci and cryptococcal pneumonia in a patient with HIV. Definitive diagnosis of PCP and Cryptococcus requires demonstration of these organisms in pulmonary tissues or fluid. In patients with < 200/microliter CD4-lymphocytes, a bronchoalveolar lavage should be performed. This patient was successfully treated with amphotericin B and trimethoprim sulfamethoxazole. After 1 week the patient showed clinical and radiologic improvement and was discharged 3 weeks later.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Bronchoalveolar Lavage Fluid; Coinfection; Cryptococcosis; Cryptococcus neoformans; Humans; Male; Microscopy; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

This retrospective review of patients with severe combined immunodeficiency and Pneumocystis jiroveci pneumonia (PCP) evaluated the relationship between duration of therapy to treat PCP and overall survival. We found that 80% of patients receiving only 21 days of antibiotics survived to 12 months beyond hematopoietic cell transplant, whereas only 25% of patients who required longer treatment for PCP survived to stem cell engraftment.

Topics: Anti-Infective Agents; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Severe Combined Immunodeficiency; Survival Analysis; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Guidelines for primary Pneumocystis jirovecii pneumonia (PCP) prophylaxis for patients with hematologic malignancy (HM) are still lacking. Our objective was to identify risk factors for PCP among patients with HM to help recognize patients who would benefit from primary PCP prophylaxis.. We performed a case-control study of adult patients with HM and negative for human immunodeficiency virus and with confirmed PCP by using cytology or histopathology from 2 medical centers over an 11-year period. Each case was matched with 4 patients without PCP by type of HM and year of treatment. We compared demographic, clinical, and laboratory data among cases and controls. Data were analyzed by using SPSS version 18.0.. Fourteen cases and 56 controls were included in the study period. No significant differences were seen in demographics between both groups. All identified patients had lymphoproliferative HM, the majority of patients (93%) had either non-Hodgkin lymphoma or chronic lymphocytic leukemia. Autoimmune diseases were more frequent in cases vs. controls (28.6% vs. 5.4% P = .01). The receipt and duration of chemotherapy were similar in both groups. Among chemotherapeutic agents, including steroids, only fludarabine was associated with increased risk for PCP (50% vs. 17.9%; P = .02). No difference was found in total or lymphocyte percentage in cases at the time of PCP diagnosis vs. nadir values in controls.. Patients with lymphoproliferative HM, specifically chronic lymphocytic leukemia and non-Hodgkin lymphoma, who are receiving fludarabine and with autoimmune disorders are at increased risk for PCP and should be considered for PCP primary prophylaxis.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Case-Control Studies; Cladribine; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vidarabine

The sulfamethoxazole (SMX)-trimethoprim drug combination is routinely used as prophylaxis against Pneumocystis pneumonia during the first 3 to 6 months after renal transplantation. The objective of this study was to examine the impact of N-acetyltransferase 2 (NAT2) and CYP2C9 polymorphisms on the pharmacokinetics of SMX in 118 renal transplant recipients. Starting on day 14 after renal transplantation, patients were administered 400 mg/day-80 mg/day of SMX-trimethoprim orally once daily. On day 14 after the beginning of SMX therapy, plasma SMX concentrations were determined by a high-performance liquid chromatography method. The SMX area under the concentration-time curve from 0 to 24 h (AUC(0-24)) for 15 recipients with the NAT2 slow acetylator genotype (NAT2 5/ 6, - 6/ 6, - 6/ 7, and - 7/ 7) was significantly greater than that for 56 recipients with the NAT2 rapid acetylator genotype (homozygous for NAT2 4) (766.4 ± 432.3 versus 537.2 ± 257.5 μg-h/ml, respectively; P = 0.0430), whereas there were no significant differences in the SMX AUC(0-24) between the CYP2C9 1/ 1 and - 1/ 3 groups. In a multiple regression analysis, the SMX AUC(0-24) was associated with NAT2 slow acetylator polymorphisms (P = 0.0095) and with creatinine clearance (P = 0.0499). Hepatic dysfunction in NAT2 slow acetylator recipient patients during the 6-month period after SMX administration was not observed. SMX plasma concentrations were affected by NAT2 polymorphisms and renal dysfunction. Although standard SMX administration to patients with NAT2 slow acetylator polymorphisms should be accompanied by monitoring for side effects and drug interaction effects from the inhibition of CYP2C9, SMX administration at a low dose (400 mg) as prophylaxis may not provide drug concentrations that reach the level necessary for the expression of side effects. Further studies with a larger sample size should be able to clarify the relationship between SMX plasma concentration and side effects.

Topics: Acetylation; Adult; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Arylamine N-Acetyltransferase; Cytochrome P-450 CYP2C9; Female; Humans; Kidney; Kidney Transplantation; Male; Middle Aged; Pneumonia, Pneumocystis; Polymorphism, Genetic; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Cortex Hormones; Anti-Infective Agents; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Bevacizumab; Breast Neoplasms; CD4 Lymphocyte Count; Clinical Trials, Phase I as Topic; Dexamethasone; Erlotinib Hydrochloride; Female; Humans; Lung Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Nitrogen Mustard Compounds; Paclitaxel; Pneumocystis carinii; Pneumonia, Pneumocystis; Quinazolines; Trimethoprim, Sulfamethoxazole Drug Combination

Recent studies suggest an increased risk for Pneumocystis jirovecii pneumonia (PJP) in adults receiving short-interval rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) therapy for diffuse large cell B cell lymphoma (DLBCL). This retrospective study evaluates precise PJP incidence and the efficacy of anti-PJP prophylaxis in DLBCL. Patients with DLBCL, aged ≥18 years and treated between December 2004 and December 2010, were included. Details of treatment-related respiratory infections, focusing on PJP incidence, risk factors and prophylaxis, were assessed. A total of 132 patients were analyzed; 47 were treated with rituximab-CHOP therapy every 21 days (R-CHOP-21) and 85 were treated every 14 days (R-CHOP-14). The incidence of treatment-related respiratory infections was higher in patients receiving R-CHOP-14. PJP was diagnosed in 5 patients: 4 in the R-CHOP-14 (6.6%) and 1 in the R-CHOP-21 cohort (2.6%), using triplex polymerase chain reaction (PCR) for PJ in bronchoalveolar fluid. None of the patients receiving P.jirovecii prophylaxis (n = 33) developed PJP, compared with 6.6% of those treated with R-CHOP-14 without such prophylaxis. An older age and R-CHOP administered every 14 rather than every 21 days increased the PJP risk. Trimethoprim/sulfamethoxazole prophylaxis is found to be highly efficient in preventing this life-threatening complication and, therefore, should be recommended for patients receiving the R-CHOP-14 regimen.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Retrospective Studies; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality.. TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models.. There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p<0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person-years.. Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antifungal Agents; Asia; CD4 Lymphocyte Count; Dapsone; Databases, Factual; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) and cytomegalovirus (CMV) infection represent possible complications of medical immunosuppression. Between 2005 and 2010, non-human immunodeficiency virus (HIV) PCP patients admitted to a nephrology unit were analyzed for outcome, CMV comorbidity, and patient-to-patient contacts prior to PCP. In contrast to 2002-2004 (no cases) and 2008-2010 (10 cases), a PCP outbreak of 29 kidney-transplant recipients and one patient with anti-glomerular basement membrane disease occurred between 2005 and 2007. None of the patients were on PCP chemoprophylaxis. In four PCP patients, the genotyping data of bronchoalveolar lavage specimen showed an identical Pneumocystis strain. PCP cases had a higher incidence of CMV infection (12 of 30 PCP patients) and CMV disease (four patients) when compared to matched PCP-free controls (p < 0.05). Cotrimoxazole and, if applicable, ganciclovir were started 2.0 ± 4.0 days following admission, and immunosuppressive medication was reduced. In-hospital mortality was 10% and the three-year mortality was 20%. CMV co-infection did not affect mortality. CMV co-infection more frequently occurred during a cluster outbreak of non-HIV PCP in comparison to PCP-free controls. Here, CMV awareness and specific therapy of both CMV infection and PCP led to a comparatively favorable patient outcome. The role of patient isolation should be further investigated in incident non-HIV PCP.

Topics: Adult; Aged; Antifungal Agents; Antiviral Agents; Case-Control Studies; Coinfection; Cross Infection; Cytomegalovirus; Cytomegalovirus Infections; Disease Outbreaks; Female; Ganciclovir; Genotype; Humans; Immunocompromised Host; Kidney Transplantation; Male; Middle Aged; Molecular Typing; Mycological Typing Techniques; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

We report the case of an 84-year-old man with refractory immune thrombocytopenia purpura (ITP) who was treated with rituximab and subsequently developed severe interstitial lung disease. There has been increasing use of rituximab in the treatment of ITP with success rates of up to 62% in adult patients with recurrent ITP. Interstitial lung disease is a rare but recognised complication of rituximab but has been rarely reported in the setting of ITP.

Topics: Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Azathioprine; Combined Modality Therapy; Disease Progression; Hemorrhage; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Pneumonia, Pneumocystis; Prednisone; Pulmonary Fibrosis; Purpura, Thrombocytopenic, Idiopathic; Rituximab; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

Solid organ transplant (SOT) recipients are at risk for Pneumocystis pneumonia (PCP), especially in the first year post transplant. Although trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis substantially decreases this risk, there is little data or consensus on optimal duration of prophylaxis. Consequently, there is lack of standardization of prophylaxis duration (3 months to lifelong, depending on organ group) in SOT programs.. We performed a retrospective chart review of all cases of confirmed PCP, in adult kidney, pancreas, liver, and lung transplant recipients from 2001 to 2011 in our SOT program.. Of 1241 patients followed in our clinic (657 kidney, 44 kidney/pancreas, 436 liver, and 104 lung or heart/lung), a total of 14 PCP cases were identified in 2 kidney, 1 kidney/pancreas, 5 liver, 5 single lung, and 1 heart/lung transplant recipient. At the time of PCP diagnosis, immunosuppression in most cases consisted of prednisone, tacrolimus, and mycophenolate mofetil (79% of patients), and 53% had previously received TMP-SMX for prophylaxis. None were on PCP prophylaxis at the time of illness onset. PCP occurred early in all 5 liver transplant recipients and in 1 kidney transplant recipient, none of whom had ever received prophylaxis (17-204 days post transplant). Of those who had received 6 months of prophylaxis (1 kidney, 1 kidney/pancreas), PCP occurred at 846 and 4778 days, respectively. Late onset PCP occurred in lung recipients who had received 12 months of prophylaxis (lung 645-1414 days, heart/lung 1583 days post transplant). Five patients had experienced acute rejection and 6 patients had cytomegalovirus (CMV) viremia on average 59 and 204 days preceding PCP, respectively. Three deaths (1 liver, 2 lung) were thought to be directly related to complications of PCP.. Our experience with late PCP cases in lung transplant recipients receiving only 1 year of prophylaxis lends support to prolonged PCP prophylaxis in this group. Given the number of patients who had experienced an acute rejection episode or CMV disease preceding PCP in non-lung SOT recipients, consideration should be given to re-institution of PCP prophylaxis for a period of time after these events in kidney, kidney/pancreas, and liver transplant recipients.

Topics: Adult; Aged; Chemoprevention; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Male; Middle Aged; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Acute Kidney Injury; Adult; AIDS-Associated Nephropathy; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Retroviral Agents; Diagnosis, Differential; HIV Seropositivity; Humans; Male; Medication Adherence; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography; Renal Dialysis; Trimethoprim, Sulfamethoxazole Drug Combination

A recent study reported that trimethoprim/sulfamethoxazole caused acute psychosis in four renal transplant patients with Pneumocystis jirovecii pneumonia. We aimed to investigate the incidence of and factors associated with trimethoprim/sulfamethoxazole-related acute psychosis in HIV-infected patients with P. jirovecii pneumonia.. We reviewed the medical records of HIV-infected patients who presented with P. jirovecii pneumonia and received trimethoprim/sulfamethoxazole at six major hospitals in Taiwan from July 2009 to May 2011. Acute psychosis was defined as the occurrence of hallucinations or delusions following the initiation of trimethoprim/sulfamethoxazole during hospitalization.. During the study period, 135 patients receiving trimethoprim/sulfamethoxazole for P. jirovecii pneumonia were enrolled and 16 (11.9%; 95% CI, 6.3%-17.4%) developed acute psychosis after a median duration of 5 days of trimethoprim/sulfamethoxazole treatment (range, 3-11 days). The incidence increased from 0% (0/16) in patients who received a daily trimethoprim dose of ≤12 mg/kg to 23.5% (4/17) in those who received a daily trimethoprim dose of >18 mg/kg. In multivariate logistic regression analysis, a higher daily dose of trimethoprim/sulfamethoxazole (OR, per 1 mg increase of trimethoprim, 1.40; 95% CI, 1.12-1.76; P = 0.0035) and use of adjunctive steroids (OR, 4.43; 95% CI, 1.14-17.15; P = 0.031) were associated with acute psychosis.. In this case series, 11.9% of HIV-infected patients developed acute psychosis while receiving trimethoprim/sulfamethoxazole for P. jirovecii pneumonia. While the study was limited by its retrospective design, the risk appeared to increase with increasing daily dose of trimethoprim/sulfamethoxazole in those vulnerable patients with multiple risks for acute psychosis.

Topics: Adult; Aged; Anti-Infective Agents; Female; HIV Infections; Humans; Male; Middle Aged; Multicenter Studies as Topic; Pneumocystis carinii; Pneumonia, Pneumocystis; Prevalence; Psychotic Disorders; Retrospective Studies; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

There are no data on the efficacy of secondary prophylaxis against Pneumocystis pneumonia after solid organ transplantation. Therefore, we investigated the rate of recurrence of Pneumocystis pneumonia after solid organ transplantation in a retrospective cohort study. Between 2005 and 2011, a total of 41 recipients recovered from Pneumocystis pneumonia. Of these, 22 (53.7%) received secondary prophylaxis. None of the 41 recipients experienced recurrence of Pneumocystis pneumonia during the follow-up, regardless of secondary prophylaxis.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Female; Humans; Male; Middle Aged; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Secondary Prevention; Trimethoprim, Sulfamethoxazole Drug Combination

Familial hepatic veno-occlusive disease with immunodeficiency (VODI, OMIM: 235550), a rare form of severe combined immune deficiency, was first described in Australian Lebanese patients as being associated with homozygous mutations in SP110, a gene encoding a PML nuclear body-associated protein. We present the first case of confirmed VODI in the United States, and identify the first novel missense mutation in SP110. The 3-year-old daughter of Hispanic parents without known consanguinity presented at age 5 months with fever, hepatomegaly, and pancytopenia. Her brother died at age 3 months from hepatic failure of undetermined etiology. Initial T- and B-cell counts were low, but eventually normalized. Serum IgG and IgM levels were low for age. Lymphoproliferation to mitogens and allogenic B-cells was normal, but absent to tetanus and candida antigens. Serum antibody levels against pneumococcal, Hib and tetanus antigens were low. Liver biopsies at ages 5 and 9 months were consistent with hepatic veno-occlusive disease or hVOD (also known as sinusoidal obstruction syndrome or SOS) and broncho-alveolar lavage detected Pneumocystis jiroveci. The patient recovered from her acute disease and has been clinically stable on immunoglobulin replacement therapy and trimethoprim-sulfamethoxazole prophylaxis. T-Cell receptor excision circle (TREC) analysis suggests that VODI will not be detected by newborn screening for severe combined immunodeficiency that relies on this assay. DNA was obtained from the patient, 4 siblings, and both parents, and SP110 was sequenced. The first missense mutation, a homozygous deletion/insertion variation in exon 2 (NM_080424.2 (SP110):c.78_79delinsAT) was detected in the patient. This novel mutation segregated in the heterozygous state in other living unaffected family members. The mechanism by which this SP110 mutation associates with VODI is consistent with the normal length mutated SP110 protein being subject to enhanced proteosome degradation resulting in marked reductions in SP110 protein.

Topics: Antibodies, Bacterial; Child, Preschool; Female; Hepatic Veno-Occlusive Disease; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Infant; Liver; Lung; Male; Minor Histocompatibility Antigens; Mutation, Missense; Nuclear Proteins; Pedigree; Pneumocystis carinii; Pneumonia, Pneumocystis; Severe Combined Immunodeficiency; Trimethoprim, Sulfamethoxazole Drug Combination

Here we present a case of refractory hypoglycaemia associated with use of the antibiotic trimethoprim-sulfamethoxazole (TMP-SMX). This was used to treat Pneumocystis jirovecii pneumonia (PCP) infection. The patient had significant pre-existing renal impairment with a kidney transplant in situ. Refractory hypoglycaemia occurred 5 days after starting the antibiotic and persisted for 36 h after its cessation. SMX contains the same sulphanilamide structural group as the oral hypoglycaemic agents called sulphonureas. SMX could therefore act as an insulin secretagogue. The inappropriately raised insulin and c-peptide levels seen in our patient support this theory. The 5-day asymptomatic period would allow sufficient time for the drug to accumulate and the extended period seen after its cessation would be seen in a dose-dependent side effect. Following 3 days of observation and continuous glycaemic support on the High Dependency Unit she was discharged back to the ward, with no further occurrence of hypoglycaemia.

Topics: Anti-Bacterial Agents; C-Peptide; Female; Humans; Hypoglycemia; Insulin; Kidney Transplantation; Middle Aged; Pneumonia, Pneumocystis; Renal Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination; White People

The concomitant use of leucovorin and cotrimoxazole in PCP can lead to therapeutic failure and increased risk of death due to antagonism. It is important to keep this possible antagonistic interaction in mind even during prophylaxis. This paper presents a case with this failure outcome.

Topics: Adult; Anti-Infective Agents; Drug Therapy, Combination; Humans; Leucovorin; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination; Vitamin B Complex

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Antibiotic Prophylaxis; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Drug Combinations; Female; Humans; Incidence; Lymphoma, B-Cell; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisolone; Rituximab; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

A 47-year-old man with optimally controlled type-2 diabetes mellitus and chronic hepatitis B was admitted to a local hospital because of a 1-week history of cough and high-grade fever. He was diagnosed with Pneumocystis pneumonia (PCP) and Klebsiella pneumonia from a chest radiograph and sputum. Simultaneously, he was found to have HIV infection with a CD4 count of 76/μl. Despite alteration of treatment secondary to the development of allergic reaction to trimethoprim-sulfamethoxazole (TMP-SMX), the patient was able to complete a 3-week therapy for PCP after being switched to pentamidine isetionate. After the treatment of PCP, he was referred to our hospital for the initiation of anti-HIV therapy. He presented with recurrent high-grade fever of a few days' duration prior to his initial visit, which subsequently led to his admission. Chest computed tomography (CT) showed the enlargement of a previously identified infiltrate in the left upper lung field, and the sputum culture upon admission was positive for Gram-positive branching rods; the organism was later identified as Nocardia exalbida. Due to his allergy to sulfonamide, the patient was treated with imipenem (IMP) and amikacin (AMK) given intravenously for 17 days, followed by garenoxacin (GRNX) taken orally for 6 months, without any adverse effects. The chest infiltrate resolved completely, and he remains stable without relapse 8 months after the completion of the therapy. Pulmonary nocardiosis should be considered as a differential diagnosis of recurring pneumonia in immunocompromised patients, especially in HIV-infected individuals. Oral administration of GRNX following IMP and AMK can be used as an alternative to TMP-SMX therapy in cases of pulmonary nocardiosis caused by N. exalbida.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Fluoroquinolones; Humans; Male; Middle Aged; Nocardia; Nocardia Infections; Pentamidine; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Sputum; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination

A retrospective study was performed on case reports of Pneumocystis pneumonia (PCP) from 1959 to 2009 in mainland China. The epidemiological characteristics of PCP over half a century were investigated over two time spans. The first was from 1959, when the first incidence of PCP was reported, to 1984, before the emergence of AIDS in mainland China. The second was from 1985, when the first AIDS case was reported in mainland China, to the end of 2009. A total of 2351 PCP cases were reported during these two time spans, covering a 51-year period. Only seven PCP cases were reported during the first time span. Six were diagnosed by autopsy, accordingly without treatment, whilst the other was diagnosed by open lung biopsy in a living patient who eventually recovered following treatment with sulfadiazine and pyrimethamine. The other 2344 PCP cases were reported during the second time span (1985-2009) from 21 provinces, four municipalities and three autonomous regions. Among the 2344 PCP cases, 70.22 % (1646/2344) were identified together with human immunodeficiency virus (HIV) infection or were in AIDS patients. The remaining 698 non-HIV-infected patients had undergone organ transplantation, had other underlying diseases such as malignancy or hypoimmunity, or had undetermined diagnosis. The results of statistical analysis indicated that AIDS was the most common underlying disease of PCP for patients <1 year and >14 years. For patients aged between 1 and 14 years, haematological malignancy was the most common underlying disease. The trend of the underlying diseases changed with time, showing that the number of PCP patients afflicted by HIV/AIDS increased dramatically, reaching almost threefold during the most recent 5 years compared with the level of the previous 10 years. The number of patients undergoing organ transplantation or with other underlying diseases rose constantly, but the number of malignancies tended to decline from 1995-2004 to 2005-2009. During the second time span (1995-2009), most of the patients (97.61 %) were diagnosed alive and only 56 cases (2.39 %) were identified by autopsy. The mortality of PCP patients treated with anti-Pneumocystis drugs was 14.61 % for those with HIV/AIDS and 15.84 % for those without HIV/AIDS. For the PCP patients without anti-Pneumocystis treatment, all (100 %) of the HIV/AIDS-associated PCP patients died, whilst 13.79 % (4/29) of non-HIV-infected PCP patients survived. These data from epidemiological investigation

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Child; Child, Preschool; China; Female; History, 20th Century; History, 21st Century; Humans; Immune System Diseases; Infant; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Transplants; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pneumocystis pneumonia is a life-threatening infection in patients undergoing chemotherapy for solid malignancies.. A 49-year-old man developed gradually increasing dyspnoea while receiving pemetrexed as a third line treatment for an adenocarcinoma of the lung. The diagnosis of pneumocystis pneumonia was based on ground-glass opacities on the thoracic CT scan and alveolar lavage revealing occasional cysts of Pneumocystis jiroveci in the context of recent lymphopenia developing during chemotherapy. Treatment with cotrimoxazole for three weeks was only partially successful due to progression of the tumour.. Pneumocystis pneumonia should be considered in cancer patients receiving antifolate drugs and presenting with increasing dyspnoea. It is important to identify a high-risk population among patients undergoing chemotherapy because of the significant morbidity and mortality and in order to administer effective prophylactic agents.

Topics: Adenocarcinoma; Antifungal Agents; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bronchoalveolar Lavage Fluid; Disease Progression; Follow-Up Studies; Glutamates; Guanine; Humans; Infusions, Intravenous; Lung Neoplasms; Male; Middle Aged; Opportunistic Infections; Pemetrexed; Pneumocystis carinii; Pneumonia, Pneumocystis; Retreatment; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

To report on the temporal relationship between administration of trimethoprim/sulfamethoxazole to medically immunosuppressed HIV-negative renal patients with Pneumocystis jirovecii pneumonia (PCP) and the development of an acute psychosis.. We investigated a retrospective case series of renal transplant and immunosuppressed patients with PCP within an ongoing outbreak in the northwest of England since 2009. Four patients with PCP developed psychosis following treatment with trimethoprim/sulfamethoxazole.. Four of twenty patients developed acute psychoses following administration of trimethoprim/sulfamethoxazole, including one accidental re-challenge. Symptoms resolved within 24 h of changing the therapy. The striking temporal relationship between the initiation and discontinuation of the drug and the behavioural changes suggests a causal relationship.. With increasing solid organ transplantation and the use of immunosuppressants, vigilance regarding trimethoprim/sulfamethoxazole dose modification is required and the routine use of therapeutic drug monitoring should be considered.

Topics: Adult; Aged; England; Female; Humans; Kidney Transplantation; Male; Mental Disorders; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Transplantation; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Small Cell; Ceftriaxone; Cisplatin; Combined Modality Therapy; Cranial Irradiation; Etoposide; Fatal Outcome; Female; Humans; Immunocompromised Host; Lung Neoplasms; Opportunistic Infections; Pneumonia, Pneumocystis; Pneumonia, Staphylococcal; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Arthritis, Rheumatoid; Contraindications; Humans; Immunosuppressive Agents; Methotrexate; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci is an important cause of mortality and morbidity among heart transplant recipients. This raises the question of prophylactic treatment for this infection. Trimethoprimsulfamethoxazole is commonly used in P. jiroveci pneumonia prophylaxis with mild to severe adverse effects. We present the use of inhaled pentamidine as P. jiroveci prophylaxis in a patient with an allergy to trimethoprim sulfamethoxazole.

Topics: Administration, Inhalation; Anti-Infective Agents; Antifungal Agents; Drug Administration Schedule; Drug Hypersensitivity; Heart Transplantation; Humans; Male; Middle Aged; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Premedication; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Risk stratification-based duration of trimethoprim-sulfamethoxazole (TMP-SMX) chemoprophylaxis to prevent Pneumocystis pneumonia (PCP) in kidney transplant recipients is not a universally adapted strategy and supporting evidence-based sources are limited. We performed a large retrospective study to identify risk factors for PCP in kidney transplant recipients and to define parameters for use in clinical prophylaxis guidelines. Fifty consecutive patients with confirmed PCP and 2 time-matched controls per case were enrolled. All patients were participants of the kidney transplantation program of the Leiden University Medical Center, a tertiary care hospital in the Netherlands. Potential risk factors were compared between groups by uni- and multivariate matched analyses. At transplantation, age >55 years (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3-5.9) and not receiving basiliximab induction therapy (adjusted OR 4.3, 95% CI 1.1-17.1) predicted development of PCP. In the final multivariate analysis, only cytomegalovirus infection (adjusted OR 3.0, 95% CI 1.2-7.9) and rejection treatment (adjusted OR 5.8, 95% CI 1.9-18) were found to be independently associated with PCP. Using the variables identified by the multivariate analyses, effects of different hypothetical chemoprophylaxis strategies were systematically evaluated. Exploring different scenarios showed that chemoprophylaxis in the first 6 months for all renal transplant patients - and during the first year posttransplantation for patients >55 years of age or those treated for rejection - would result in very low PCP incidence and optimal avoidance of TMP-SMX toxicity. The results provide a rationale for further prospective study on targeted provision of chemoprophylaxis to prevent PCP in kidney transplant patients.

Topics: Adult; Age Factors; Antibiotic Prophylaxis; Antibodies, Monoclonal; Basiliximab; Cohort Studies; Cytomegalovirus; Cytomegalovirus Infections; Female; Graft Rejection; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Complications; Recombinant Fusion Proteins; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Diagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented.. We compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77-90% of patients at $26-51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68-90% of patients at costs of $189-232 per life-year gained. A relatively cost-effective diagnostic procedure that did not require PCR was Toluidine Blue O staining of induced sputum ($25 per life-year gained, successfully treating 68% of patients). Diagnosis using chest x-rays alone resulted in successful treatment of 77% of patients, though cost-effectiveness was reduced ($109 per life-year gained) compared with several molecular diagnostic options.. For diagnosis of PCP, use of PCR technologies, when combined with less-invasive patient specimens such as expectorated or induced sputum, represent more cost-effective options than any diagnostic procedure using BAL, or chest x-ray alone.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Clinical Laboratory Techniques; Cost of Illness; Cost-Benefit Analysis; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prevalence; Reproducibility of Results; Sensitivity and Specificity; South Africa; Sputum; Staining and Labeling; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Cough; Dyspnea; Fluorescent Antibody Technique, Direct; Humans; Male; Microscopy; Mycology; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination; Weight Loss

The aim of our study was to examine the primary prophylactic effect of sulfamethoxazole/trimethoprim single strength (SMZ/TM SS) against Pneumocystis jirovecii pneumonia (PCP) in connective tissue disease (CTD) patients with immune dysfunction induced by the long-term use of prednisolone. Prevalence of adverse drug reactions (ADRs) to sulfonamide in these patients was the secondary outcome.. This was a retrospective cohort study. Medical records of CTD patients who were treated with prednisolone ≥20 mg per day or equivalent doses of corticosteroid for more than 2 weeks and were followed for at least 12 weeks after receiving this dosage of corticosteroids at the Rheumatology clinic of Ramathibodi Hospital between October 2006 and September 2007 were reviewed. Information regarding clinical status, laboratory features, and clinical course of the enrolled subjects was recorded.. There were 138 episodes of PCP risk in 132 CTD patients; 59 episodes received SMZ/TM SS, while 79 episodes did not. All 6 PCP cases developed in patients without prophylaxis with an overall incidence of 4.3%. The incidence of PCP between the 2 groups was significantly different (P = 0.038). Absolute risk reduction and relative risk reduction were 7.3% and 100%, respectively. All ADR developed in 5 systemic lupus erythematosus patients (8.5%): 4 had drug rashes and 1 had mild hepatitis. There was no correlation between the use of, or allergic reactions to, SMZ/TM and lupus flare.. Sulfamethoxazole/trimethoprim single strength can be used effectively as a primary prophylaxis against PCP in high-risk CTD patients. Only mild ADR developed at this dosage. Further evaluations in larger groups of CTD patients are warranted.

Topics: Adult; Anti-Infective Agents; Antibiotic Prophylaxis; Connective Tissue Diseases; Female; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Respiratory infections are of particular concern in transplant patients. However, there is a significant overlap in the symptoms caused by different pathogens. Here, we report a case of Pneumocystis jiroveci pneumonia (PCP) in a renal transplant patient which was initially misdiagnosed as pandemic influenza H1N1. The patient did not improve under oseltamivir treatment and bronchoscopy was performed five days later after hospitalization. PCP was diagnosed by microscoping evaluation of bronchoalveolar lavage (BAL) fluid. Besides, BAL and serum of the patient yielded a large amount of 1,3-beta-D-glucan, a cellwall compotent of medically important mycoses including P. jiroveci. The patient was successfully treated with intravenous trimethoprim-sulfamethoxazole. Due to the lack of sensitivity of influenza case definitions, the attending physicians should be careful about alternative diagnoses particularly in transplant patients with severe respiratory infections.

Topics: Adult; Anti-Infective Agents; Bronchoalveolar Lavage; Diagnosis, Differential; Diagnostic Errors; Humans; Immunocompromised Host; Influenza A Virus, H1N1 Subtype; Influenza, Human; Injections, Intravenous; Kidney Transplantation; Male; Pandemics; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

While tumor necrosis factor (TNF) inhibitors have dramatically improved the clinical outcomes of rheumatoid arthritis (RA) in recent years, infectious complications are a serious concern. Adalimumab (ADA) is a newly-developed human monoclonal antibody against TNF-alpha. Here we report 2 cases of pneumocystis pneumonia (PCP) which developed in RA patients during ADA therapy. One patient is a 66-year-old woman who had a history of RA for 6 months. The patient was given ADA at 40 mg biweekly for her active arthritis which had been refractory to 6 mg/week of methotrexate (MTX), and 5 mg/day of prednisolone (PSL). One hundred and six days later, she was admitted to our hospital because of fever, cough, and dyspnea. Another patient is a 62-year-old man who had a history of RA for 3 years. Since his arthritis was so active even under the treatment with MTX (8 mg/week) and PSL (15 mg/day), the patient started to be given ADA at 40 mg biweekly. After 28 days, the patient was admitted to the hospital because of dyspnea. Chest roentgenogram and computed tomography revealed interstitial pneumonia in both patients. Beta-D-glucan levels were so high in their serum suggesting the diagnosis of PCP, which was confirmed by the detection of Pneumocystis jirovecii DNA in the sputa by polymerase chain reaction. The patients were immediately treated with sulfamethoxazole/trimethoprim and high-dose prednisolone, which successfully improved pneumonia, and they were discharged from the hospital on the 8(th) and 16(th) day, respectively. PCR and β-D-glucan were useful for the early diagnosis of PCP and lead to the timely induction of adequate treatment and the rescue of these patients.

Topics: Adalimumab; Aged; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; beta-Glucans; Biomarkers; DNA, Fungal; Early Diagnosis; Female; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prednisolone; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

Prophylaxis against Pneumocystis jirovecii pneumonia (PCP) is recommended for at least 4-12 months after solid organ transplant. In our center, renal transplant recipients receive only 1 month of post-transplant trimethoprim-sulfamethoxazole, which also may provide limited protection against Nocardia. We identified only 4 PCP cases and 4 Nocardia cases in 1352 patients receiving renal and renal-pancreas transplant from 2003 to 2009 at the University of Michigan Health System. Two PCP cases were identified <1 year after transplant, and 2 PCP cases were identified >1 year after transplant (gross attack rate 4/1352, 0.3%). Two Nocardia cases were identified <1 year after transplant, and 2 cases were identified >1 year after transplant. All identified cases received induction therapy (7 of 8 with anti-thymocyte globulin), whereas about one-half of all renal transplant patients received induction therapy at our institution. No patient was treated for rejection within 6 months of PCP; 2 of 4 patients with PCP had recent cytomegalovirus infection. All patients with PCP and 3 of 4 patients with Nocardia survived. The benefits of prolonged PCP prophylaxis should be weighed against the adverse events associated with prolonged use of antimicrobials.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Drug Administration Schedule; Humans; Immunocompromised Host; Immunosuppression Therapy; Kidney Transplantation; Nocardia Infections; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Complications; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Choroiditis; Female; HIV Infections; Humans; Pneumocystis; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Curative and prophylactic therapy for Pneumocystis jiroveci pneumonia relies mainly on cotrimoxazole, an association of trimethoprim and sulfamethoxazole (SMX). SMX inhibits the folic acid pathway through competition with para-aminobenzoic acid (pABA), one of the two substrates of the dihydropteroate synthase (DHPS), a key enzyme in de novo folic acid synthesis. The most frequent non-synonymous single nucleotide polymorphisms (SNPs) in P. jiroveci DHPS are seen at positions 165 and 171, the combination leading to four possible different genetic alleles. A number of reports correlate prophylaxis failure and mutation in the P. jiroveci DHPS but, because of the impossibility of reliably cultivating P. jiroveci, the link between DHPS mutation(s) and SMX susceptibility is not definitively proven. To circumvent this limitation, the yeast Saccharomyces cerevisiae was used as a model. The introduction of the P. jiroveci DHPS gene, with or without point mutations, directly amplified from a clinical specimen and cloned in a centromeric plasmid into a DHPS-deleted yeast strain, allowed a fully effective complementation. However, in the presence of SMX at concentrations >250 mg/L, yeasts complemented with the double mutated allele showed a lower susceptibility compared with strains complemented with either a single mutated allele or wild-type alleles. These results confirm the need for prospective study of pneumocystosis, including systematic determination of the DHPS genotype, to clarify further the impact of mutations on clinical outcome. Additionally, the S. cerevisiae model proves to be useful for the study of still uninvestigated biological properties of P. jiroveci.

Topics: Antifungal Agents; Dihydropteroate Synthase; Drug Resistance, Fungal; Genes, Fungal; Genetic Complementation Test; Humans; Microbial Sensitivity Tests; Pneumocystis carinii; Pneumonia, Pneumocystis; Saccharomyces cerevisiae; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecci is an opportunist fungal agent that usually causes pneumonia in immunocompromised patients, particularly those presenting with AIDS. In rare cases, this fungus can cause pneumonia in immunocompetent patients. The symptomatology in this case is acute and fulminant. We report the case of a Pneumocystis jirovecci pneumonia in a young patient initially admitted for acute respiratory distress. This case is unusual since all the exams performed to screen for immune deficit were negative. The diagnosis was made after identifying Pneumocystis jirovecci cysts in broncho-alveolar lavage.

Topics: Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Drug Therapy, Combination; Female; Humans; Immunocompetence; Methylprednisolone; Pneumocystis carinii; Pneumonia, Pneumocystis; Respiratory Distress Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

The T cell-mediated immune response elicited by Pneumocystis plays a key role in pulmonary damage and dysfunction during Pneumocystis carinii pneumonia (PcP). Mice depleted of CD4(+) and CD8(+) T cells prior to infection are markedly protected from PcP-related respiratory deficit and death, despite progressive lung infection. However, the therapeutic effectiveness of Ab-mediated disruption of T cell function in mice already displaying clinical symptoms of disease has not been determined. Therefore, a murine model of PcP-related immune reconstitution inflammatory syndrome was used to assess whether Ab to the pan-T cell molecule CD3 is effective for reducing the severity of PcP when administered after the onset of disease. Mice that received anti-CD3 Ab exhibited a rapid and dramatic halt in the PcP-associated pulmonary function decline within 1 week after treatment, and a striking enhancement of survival rate compared with mice receiving the control Ab. Physiologic improvement in anti-CD3 treated mice was associated with a significant reduction in the number of CD4(+) and CD8(+) T cells recovered in lung lavage fluid. This effectiveness of anti-CD3 was noted whether the mice also received antibiotic therapy with trimethoprim-sulfamethoxazole. These data suggest that monoclonal Ab-mediated disruption of T cell function may represent a specific and effective adjunctive therapy to rapidly reverse the ongoing pathologic immune response occurring during active PcP. Thus, the anti-human CD3 monoclonal Ab OKT3, which is already in clinical use, has the potential to be developed as an adjunctive therapy for PcP.

Topics: Animals; Anti-Infective Agents; Antibodies; Bronchoalveolar Lavage Fluid; CD3 Complex; Disease Models, Animal; Inflammation; Lymphocyte Depletion; Mice; Pneumonia, Pneumocystis; Reverse Transcriptase Polymerase Chain Reaction; Trimethoprim, Sulfamethoxazole Drug Combination

The clinical features of pneumocystis pneumonia (PCP) differ according to the predisposing factors responsible for immunosuppression. Although PCP in patients with acquired immunodeficiency syndrome (AIDS) has been extensively described, its characteristics in non-AIDS patients, such as those with malignancies, are not thoroughly documented.. To characterize and compare the clinical and imaging features of PCP in patients with malignancies with those in AIDS patients.. A multi-center retrospective study.. We evaluated the clinical and radiological features of PCP in 21 patients with malignancies and in 17 with AIDS. Clinical presentation, serum markers, oxygenation, CT findings, and outcome were examined.. The patients with malignancies showed shorter durations of symptoms before PCP was diagnosed. The levels of serum markers and the oxygenation index did not differ. CT showed diffuse or widespread ground-glass opacity (GGO) in all of the patients evaluated. None of the AIDS patients demonstrated consolidation, whereas half of the patients with malignancy showed consolidation along with GGO. The extent of GGO scored on CT images was significantly greater in the AIDS patients. No correlation was observed between the CT findings and other clinical parameters. All of the AIDS patients recovered from PCP, whereas six patients with malignancies died within a month after the onset of PCP.. The characteristics of the CT images differed between the patient groups with different underlying disorders, although it remains to be determined whether CT findings are associated with other clinical features or are predictive of the outcome of PCP.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Biomarkers; Female; Humans; Leukocyte Count; Male; Middle Aged; Neoplasms; Oxygen; Pneumonia, Pneumocystis; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-Rhabdomyolysis is a serious, potentially life-threatening complication diagnosed when creatine phosphokinase levels exceed 1000 U/L. Although many drugs are associated with rhabdomyolysis, the previous reports of trimethoprim-sulfamethoxazole (TMP/SMX)-induced rhabdomyolysis have involved patients with human immunodeficiency virus/acquired immunodeficiency syndrome. This is the first report, to our knowledge, of TMP/SMX-induced rhabdomyolysis in an allogeneic stem cell transplant patient.

Topics: Adult; Anti-Infective Agents; Creatine Kinase; Female; Hematopoietic Stem Cell Transplantation; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Rhabdomyolysis; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

We report on a patient with Pneumocystis jirovecii pneumonia who developed fever, rash, eosinophilia and hepatitis 10 days after initiation of a therapy with sulfamethoxazole and trimethoprim. A DRESS syndrome was diagnosed and the therapy was changed successfully to pyrimethamine and dapsone. We describe the clinical picture, causative drugs, pathogenesis, differential diagnoses and therapy of this life-threatening disease to acquaint the general practitioner with it.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Diagnosis, Differential; Doxorubicin; Drug Eruptions; Drug Hypersensitivity; Eosinophilia; Exanthema; Fever of Unknown Origin; Humans; Liver Function Tests; Lymphoma, T-Cell; Male; Middle Aged; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

Topics: Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The objective of this study was to determine whether the prevalence of Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations has changed since the introduction of combined antiretroviral therapy (cART) and whether the mutations are associated with poor outcome in Spanish HIV-1-infected patients with Pneumocystis pneumonia (PcP). We studied 167 PcP episodes in HIV-1-infected patients diagnosed during the pre-cART (1989-1995) and cART (2001-2004) periods. Molecular genotyping of DHPS was successfully performed in 98 patients (43 pre-cART and 55 cART). Seventeen patients (17/98, 17%; 95% confidence interval [CI], 10-25%) had mutations in the DHPS gene: 14 patients (14/43, 33%; 95% CI, 19-49%) from the pre-cART period and 3 patients (3/55, 5.5%; 95% CI, 1.3-16%) from the cART period (P < 0.01). In the multivariate analysis, the pre-cART period, previous PcP prophylaxis with sulfa drugs, and homosexuality as an HIV risk factor were found to be associated with a higher risk of presenting DHPS mutations. Overall, 95% of patients were treated with trimethoprim and sulfamethoxazole (TMP-SMX). In-hospital mortality was similar in patients with (out) mutations (6% versus 11%, P = 0.84). DHPS gene mutations were more common during the pre-cART period and were associated with previous sulfa exposure and homosexuality. However, their presence did not worsen prognosis of PcP. The response to TMP-SMX with therapeutic doses was successful in most cases.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Dihydropteroate Synthase; Genotype; HIV Infections; HIV-1; Hospital Mortality; Humans; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Prevalence; Spain; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the extent of elimination of trimethoprim (TMP) and sulfamethoxazole (SMX) via continuous venovenous hemodiafiltration (CVVHDF) in 2 critically ill patients with renal failure.. A 62-year-old woman with Pneumocystis jirovecii pneumonia (PCP) was admitted to our intensive care unit for severe acute respiratory distress syndrome. A 77-year-old man was admitted for aortic root replacement and developed septic shock and nosocomial pneumonia due to Stenotrophomonas maltophilia. Both patients developed acute renal failure, necessitating CVVHDF. They were treated with intravenous TMP/SMX adapted to renal function. The first patient received TMP 6.4 mg/kg/day and SMX 32 mg/kg/day, corresponding to 50% of the recommended high-dose TMP/SMX regimen in PCP patients. The second patient received TMP 1.7 mg/kg/day and SMX 8.6 mg/kg/day, corresponding to 50% of the usual dose in bacterial infections. We determined peak and trough serum TMP and SMX concentrations and the extent of TMP/SMX CVVHDF clearance at steady-state while the patients were still anuric and oliguric.. Data on TMP and SMX pharmacokinetics in CVVHDF are lacking and dosing recommendations are inconclusive. In both patients, CVVHDF clearance of TMP ranged from 21.5 to 28.9 mL/min, corresponding with normal renal clearance (20-80 mL/min). SMX clearance in CVVHDF showed high variability (18.7, 26.7, and 42.6 mL/min) and exceeded renal clearance values in normal renal function (1-5 mL/min). Accordingly, peak TMP serum concentrations were within the recommended range in the patient treated with a reduced TMP/SMX dose for PCP, whereas her SMX peak concentrations were only one third of recommended target concentrations.. Our data indicate that both TMP and SMX are removed by CVVHDF to a significant degree, and dose reduction of TMP/SMX in CVVHDF bears the risk of underdosing. Given variability in drug exposure in critically ill patients, therapeutic drug monitoring is advisable in anuric or oliguric patients undergoing continuous renal replacement therapy to ensure optimal TMP/SMX dosing.

Topics: Acute Kidney Injury; Aged; Anti-Infective Agents; Critical Illness; Cross Infection; Female; Gram-Negative Bacterial Infections; Hemodiafiltration; Humans; Infusions, Intravenous; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

Adverse drug reactions occur at a greater frequency in HIV-infected individuals. A 38-year-old Eritrean man was treated with outpatient co-trimoxazole for confirmed Pneumocystis jirovecii pneumonia, but was switched to clindamycin and primaquine due to nausea and vomiting. Following development of methaemaglobinaemia, he was recommenced on prophylactic co-trimoxazole. He was later found moribund with features resembling septic shock and required invasive respiratory support. The diagnosis of a rare, but severe reaction to co-trimoxazole did not become apparent until he was rechallenged with prophylactic co-trimoxazole after recovery from his initial severe reaction. In an era of polypharmacy and an increasing availability of novel drugs, this case is a timely reminder to clinicians of the ongoing need for pharmacovigilance, especially in HIV-infected individuals who may have unusual presentations of an adverse drug reaction.

Topics: Adult; Anti-Infective Agents; HIV Infections; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Shock, Septic; Trimethoprim, Sulfamethoxazole Drug Combination

An increasing incidence of Pneumocystis jiroveci pneumonia (PCP) in patients with B-cell non-Hodgkin lymphoma (B-NHL) receiving rituximab treatment has been reported. We reviewed patients with B-NHL who underwent chemotherapy from 2004 to 2008 at our institution to identify risk factors for PCP development during and after chemotherapy. Among 297 patients with B-NHL, six developed PCP. Of 121 patients (41%) who received PCP prophylaxis with sulfamethoxazole–trimethoprim during chemotherapy, none developed PCP (0%), while among 176 patients (59%) who had no prophylaxis, six (3.4%) developed PCP at a median of 2 months (range: 1–3 months) after starting chemotherapy. Patients with CD4+ lymphocyte counts ≤200/mm3 before chemotherapy had a higher risk of developing PCP (p=0.045), while a history of rituximab treatment was not related to PCP. CD4+ lymphocyte counts ≤200/mm3 during and after chemotherapy were observed in 18.9% of patients.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; CD4 Lymphocyte Count; CD4-CD8 Ratio; Drug Therapy, Combination; Female; Humans; Lymphoma, B-Cell; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Assessment; Risk Factors; Rituximab; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Cotrimoxazole, an association of trimethoprim and sulfamethoxazole, and dapsone, are mainstays for the prophylaxis and treatment of Pneumocystis pneumonia (PcP). The inability to culture Pneumocystis prevents routine susceptibility testing and detection of drug resistance. Instead, molecular techniques have been used to detect Pneumocystis jiroveci dihydropteroate synthase (DHPS) mutations that cause sulfa resistance in other microorganisms. The most frequent DHPS mutations occur at nucleotide positions 165 and 171, which lead to an amino acid change at positions 55 and 57. Several studies suggest that these mutations are associated with the failure of chemoprophylaxis for PcP. The aim was to establish the frequency and characteristics of P jiroveci DHPS mutations among colonized individuals and PcP patients from Spain. A total of 50 colonized individuals and 25 PcP patients were studied. DHPS polymorphisms were identified by restriction fragment length polymorphism assay. The analysis provided a rate of 28% of DHPS gene mutations in our population, with the presence of all possible polymorphisms described. The presence of mutations was higher in PcP patients than in colonized subjects (40% vs 22%), probably because of the chemoprophylaxis used in PcP patients. The comparison between patients with and without DHPS mutations did not show statistical differences due to age, sex, steroid use, sulfa drug exposure, or smoking. A high rate of DHPS mutations in our area of Spain, not only confined to patients previously exposed to sulfa drugs, is shown in this study. As well as PcP patients, colonized individuals who harbor P jiroveci strains with DHPS mutations could play a major role in the transmission cycle of these mutations, representing a reservoir and source of infection for susceptible individuals. Further research is thus warranted to assess the true scope of the problem and to design rational preventive strategies.

Topics: Adult; Age Distribution; Aged; Antifungal Agents; Cohort Studies; Dihydropteroate Synthase; Disease Reservoirs; DNA, Fungal; Drug Resistance, Fungal; Female; Follow-Up Studies; Gene Expression Regulation, Fungal; Genotype; Humans; Incidence; Male; Microbial Sensitivity Tests; Mutation; Mycological Typing Techniques; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Risk Assessment; Sex Distribution; Spain; Statistics, Nonparametric; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

We report two cases of Pneumocystis jiroveci pneumonia (PCP) with CD20(+) B-cell lymphoma. They were treated by several courses of CHOP-based chemotherapy containing rituximab. We confirmed by flow cytometric analysis that both of them completely lost CD19(+) and CD20(+) B-cells from their peripheral blood after the first course of chemotherapy. They were successfully treated with Trimethoprim-sulfamethoxazole (TMP-SMX) after the diagnosis of PCP by polymerase chain reaction (PCR). We overviewed CD20(+) B-cell lymphoma patients treated with CHOP-based regimens from 1997 until 2005 in our hospital. We treated 114 patients with and 121 patients without rituximab. Five patients in the group with rituximab developed interstitial pneumonia (IP). Two of them were confirmed to have PCP and the other three were suspected cases ; however, no patients with IP were seen in the group without rituximab. We strongly suggest the necessity of PCP prophylaxis with oral TMP-SMX when treating B-cell lymphoma patients with chemotherapy containing rituximab.

Topics: Aged; Anti-Infective Agents; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Flow Cytometry; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prednisone; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

Topics: Anti-Infective Agents; Clinical Protocols; Developing Countries; HIV Infections; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Infections in solid-organ transplant recipients are the most important causes of morbidity and mortality. A primary goal in organ transplant is the prevention or effective treatment of infection, which is the most common life-threatening complication of long-term immunosuppressive therapy. A 21-year-old woman who underwent heart transplant 3 years previous owing to dilated cardiomyopathy was referred to our hospital with symptoms of high fever and cough. The patient's history revealed that she had received a trimethoprim-sulfamethoxazole double-strength tablet each day for prophylactic purposes. On chest radiograph, pneumonia was detected, and in broncho-alveolar lavage sample, Pneumocystis jiroveci cysts were found. After diagnosing P. jiroveci pneumonia, trimethoprim-sulfamethoxazole was initiated at 20 mg/kg/d including intravenous trimethoprim in divided dosages every 6 hours. On the sixth day of therapy, she died in intensive care unit. In solid-organ transplant recipients, although antipneumocystis prophylaxis is recommended within the first 6 to 12 months after transplant, lifelong prophylaxis is also used in several settings. In addition, the physician should keep in mind that P. jiroveci pneumonia may develop in solid organ recipients, despite trimethoprim-sulfamethoxazole prophylaxis.

Topics: Anti-Infective Agents; Antibiotic Prophylaxis; Fatal Outcome; Female; Heart Transplantation; Humans; Immunosuppressive Agents; Pneumocystis carinii; Pneumonia, Pneumocystis; Time Factors; Tomography, X-Ray Computed; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

We report a death case of a man in his sixties with pneumocystis pneumonia during chemotherapy for gastric cancer. He was diagnosed with cStage IIIB (T4a, N2, H0, P0, M0). Because of bulky N2, systemic chemotherapy of S-1 and CDDP was performed from April 2009. But no reductions were noted after 2 courses. We next treated this patient with S-1 and CPT-11. He had also received corticosteroid treatment for nausea. Because of high fever and choke, he came to our hospital at day 12 in 3 courses, and a severe respiratory failure occurred. CT of the chest showed diffuse ground-glass bilateral opacities, and we immediately started a treatment with trimethoprim-sulfamethozazole and corticosteroid for the possibility of pneumocystis pneumonia. We finally deduced pneumocystis pneumonia from markedly elevated serum beta-D-glucan and PCR positive after hospitalization. In spite of early treatments, he died of bacterial pneumonia and gastric cancer. We should be careful of pneumocystis pneumonia during chemotherapy and corticosteroid treatment.

Topics: Antineoplastic Agents, Phytogenic; Camptothecin; Dexamethasone; Drug Combinations; Fatal Outcome; Glucocorticoids; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Pneumonia, Pneumocystis; Stomach Neoplasms; Tegafur; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations' (55th and 57th codon) association with prior sulfa prophylaxis failure has been reported from both developed and developing countries. We conducted a prospective study to determine the prevalence of P. jirovecii DHPS mutations from 2006 to 2009 on P. jirovecii isolates obtained from HIV-infected patients with a clinical diagnosis of Pneumocystis carinii pneumonia (PCP) admitted to our tertiary care reference health center in New Delhi, India.. Detection of P. jirovecii cysts was performed by direct fluorescent antibody (DFA) staining and by Grocott's-Gomori methenamine silver staining (GMS). DNA detection was performed by polymerase chain reaction (PCR) using primers for the major surface glycoprotein (MSG) gene. P. jirovecii DHPS gene was amplified by nested PCR protocol and sequenced for detecting mutations at the 55th and 57th codons.. Out of 147 HIV-positive patients with suspected Pneumocystis pneumonia (PCP), 16 (10.8%) PCP positive cases were detected. Of 16 cases, nine (56.2%) were positive by DFA staining, four (25%) were positive by Grocott's-Gomori methenamine silver staining, and all 16 were positive by MSG PCR. DHPS mutations at the 55th and 57th codons were observed in 6.2% of HIV patients studied, which was relatively low compared to reports from developed nations..   Prevalence of Pneumocystis jirovecii DHPS mutations associated with cotrimoxazole treatment failure may be low in the Indian subpopulation of HIV-positive patients and warrants larger studies to elucidate the true picture of Pneumocystis jirovecii sulfa drug resistance in India.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dihydropteroate Synthase; Drug Resistance, Fungal; Female; HIV Infections; Humans; India; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prevalence; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

To report hypoglycaemia, a life-threatening adverse event, associated with trimethoprim-sulfamethoxazole. A sulfonylurea-like effect, leading to insulin raise, was investigated.. Two cases of trimethoprim-sulfamethoxazole-associated hypoglycaemia in 2 patients with a diagnosis of new HIV-1-infection presenting with Pneumocystis jiroveci pneumonia are reported. The patients had no predisposing factors, such as renal or liver impairment, interfering with trimethoprim-sulfamethoxazole elimination, thus leading to hypoglycaemia. Insulin plasma levels were measured in both patients.. Severe hypoglycaemia was associated with increased serum levels of insulin up to 84 microU/ml (normal values < 10 microU/ml). Continuous dextrose infusion was necessary, further suggesting the sulfonylurea-like effect of sulfamethoxazole. Interestingly, plasma levels of insulin progressively raised after trimethoprim-sulfamethoxazole administration.. Only 18 cases of trimethoprim-sulfamethoxazole associated hypoglycaemia are reported in the literature. Hypoglycaemia is a life-threatening condition, likely underreported, to consider when trimethoprim-sulfamethoxazole administration is required, even in the absence of predisposing factors or other hypoglycaemic agents. Physician should bear in mind the potential trimethoprim-sulfamethoxazole-associated adverse event especially when prolonged treatments and elevated dosage are used.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Blood Glucose; Female; Glucose; Humans; Hypoglycemia; Insulin; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Severity of Illness Index; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pneumocystis pneumonia (PCP) is an opportunistic infection caused by Pneumocystis jirovecii (P. jirovecii) in humans. We reported a 23 year-old male patient who developed pneumonia after renal transplantation. P. jirovecii cysts and trophozoites were detected in bronchoalveolar lavage (BAL) samples of the patient by Giemsa, methenamine-silver and Toluidine-O staining. The patient, who was diagnosed as PCP, was discharged as he recovered by 21 days trimethoprim-sulfamethoxazole (TMP-SMX) therapy. This case, who developed PCP even though he had received prophylaxis after transplantation, was reported to emphasize the importance of the agent in immunocompromised patients.

Topics: Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Humans; Immunocompromised Host; Kidney Transplantation; Male; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pneumocystis jivorecii (formerly known as carinii) pneumonia (PCP) is potentially a life-threatening opportunistic infection after organ transplantation, occurring most frequently in the first 12 months, where the incidence rate is several-fold higher than in later years. PCP typically presents with fever, cough, dyspnoea and hypoxia. In organ transplant recipients, the onset of symptoms is generally more fulminant compared to patients infected with the human immunodeficiency virus. We present a patient who developed PCP five years after a renal transplantation. His presentation was characterised by atypical symptoms and an indolent onset. Previous acute vascular rejection, ongoing maintenance prednisolone usage, cytomegalovirus seropositivity and past tuberculous infection may have predisposed this patient to PCP.

Topics: Anti-Infective Agents; Bronchoscopy; Cytomegalovirus Infections; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Pleural Effusion; Pneumonia, Pneumocystis; Prednisolone; Radiography, Thoracic; Risk Factors; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations are associated with failure of sulfur prophylaxis of Pneumocystis pneumonia. Here the P. jirovecii DHPS gene was amplified from bronchoalveolar fluid of 10 AIDS patients in China. No DHPS gene mutations were observed. The results suggest that the prevalence of DHPS mutations in China may be low.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Antifungal Agents; Bronchoalveolar Lavage Fluid; China; Dihydropteroate Synthase; Female; Genes, Fungal; Humans; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To establish proper management of Pneumocystis jiroveci pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with infliximab. PCP has been observed in 0.4% of patients with RA treated with infliximab in Japan.. Data from patients with RA (n = 21) who were diagnosed with PCP during infliximab treatment and from 102 patients with RA who did not develop PCP during infliximab therapy were collected from 14 rheumatology referral centers in Japan. A retrospective review of these patients and a case-control study to compare patients with and without PCP were performed.. The median length of time from the first infliximab infusion to the development of PCP was 8.5 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 7.5 mg/day and 8 mg/week, respectively. Pneumocystis jiroveci was microscopically identified in only 2 patients, although the polymerase chain reaction test for the organism was positive in 20 patients. The patients with PCP had significantly lower serum albumin levels (P < 0.001) and lower serum IgG levels (P < 0.001) than the patients without PCP. Computed tomography of the chest in all patients with PCP revealed ground-glass opacity either with sharp demarcation by interlobular septa or without interlobular septal boundaries. Sixteen of the 21 patients with PCP developed acute respiratory failure, but all survived.. PCP is a serious complication that may occur early in the course of infliximab therapy in patients with RA. For the proper clinical management of this infectious disease, physicians need to be aware of the possibility of PCP developing during infliximab therapy.

Topics: Aged; Anti-Infective Agents; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Humans; Infliximab; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cholestasis, Intrahepatic; Humans; Immunocompromised Host; Magnetic Resonance Imaging; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

We report the case of a 21-year-old man who was noted to have pneumomediastinum during an admission for an acute flare of ulcerative colitis. At that time, he was on maintenance treatment with azathioprine at a dose of 1.25 mg/kg per day, and had not received supplementary steroids for 9 mo. He had never received anti-tumor necrosis factor (TNF)alpha therapy. Shortly after apparently effective treatment with intravenous steroids and an increased dose of azathioprine, he developed worsening colitic and new respiratory symptoms, and was diagnosed with Pneumocystis jiroveci (carinii) pneumonia (PCP). Pneumomediastinum is rare in immunocompetent hosts, but is a recognized complication of PCP in human immunodeficiency virus (HIV) patients, although our patient's HIV test was negative. Treatment of PCP with co-trimoxazole resulted in resolution of both respiratory and gastrointestinal symptoms, without the need to increase the steroid dose. There is increasing vigilance for opportunistic infections in patients with inflammatory bowel disease following the advent of anti-TNFalpha therapy. This case emphasizes the importance of considering the possibility of such infections in all patients with inflammatory bowel disease, irrespective of the immunosuppressants they receive, and highlights the potential of steroid-responsive opportunistic infections to mimic worsening colitic symptoms in patients with ulcerative colitis.

Topics: Adolescent; Animals; Anti-Infective Agents; Colitis, Ulcerative; Humans; Immunosuppressive Agents; Male; Mediastinal Emphysema; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha; Young Adult

Sulfamethoxazole in combination with trimethoprim (cotrimoxazole) is used for prophylaxis and treatment of several opportunistic infections in HIV-infected patients. It is associated with a high incidence of hypersensitivity reactions, which is thought to have an immune basis. Genetic polymorphisms in MHC are known to predispose to hypersensitivity reactions to a structurally diverse group of drugs in HIV-positive patients. The aim of the study was to determine whether functional polymorphisms in TNF, LTA, HSPA1L and HLA-DRB1 genes influence the risk of cotrimoxazole hypersensitivity in HIV-infected patients.. We genotyped 136 HIV-positive patients with (n = 53) and without (n = 83) cotrimoxazole hypersensitivity using a combination of PCR-based techniques, including PCR-restriction fragment length polymorphisms, PCR-sequence specific oligonucleotides and real-time PCR. Genotypes and the haplotype frequencies were analyzed using the chi(2) test in the Haploview and CLUMP programs.. No statistically significant difference in SNP or haplotype frequencies were found in HIV-infected sulfamethoxazole hypersensitive patients compared with controls.. Our data show that MHC polymorphisms are not major predisposing factors for cotrimoxazole hypersensitivity, although we cannot exclude a minor contribution. An environmental factor (i.e., HIV infection) seems to predominate over any of the genetic factors so far investigated in increasing the risk of cotrimoxazole hypersensitivity.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Hypersensitivity; Female; Haplotypes; HLA-DR Antigens; HLA-DRB1 Chains; HSP70 Heat-Shock Proteins; Humans; Lymphotoxin-alpha; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

Topics: Acute Kidney Injury; Adenine; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Fatal Outcome; Humans; Kidney Diseases; Male; Middle Aged; Multiple Organ Failure; Organophosphonates; Pneumocystis carinii; Pneumonia, Pneumocystis; Recurrence; Renal Dialysis; Tenofovir; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Renal

Topics: Female; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

2009 marks the 100th anniversary of the first description of Pneumocystis, an organism that was ignored for much of its first 50 years but that has subsequently been recognized as an important pathogen of immunocompromised patients, especially patients infected with human immunodeficiency virus (HIV). We present a patient with chronic lymphocytic leukemia who died from Pneumocystis pneumonia (PCP) despite appropriate anti-Pneumocystis therapy. Although substantial advances in diagnosis, treatment, and prevention of PCP have decreased its frequency and improved prognosis, PCP continues to be seen in both HIV-infected patients and patients receiving immunosuppressive medications. Pneumocystis species comprise a family of fungi, each of which appears to be able to infect only 1 host species. Pneumocystis has a worldwide distribution. Immunocompetent hosts clear infection without obvious clinical consequences. Pneumocystis has been identified in patients with other diseases such as chronic obstructive pulmonary disease, although its clinical impact is uncertain. Immunocompromised patients develop disease as a consequence of reinfection and possibly reactivation of latent infection. In patients with HIV infection, the CD4 count is predictive of the risk for developing PCP, but such reliable markers are not available for other immunocompromised populations. In the majority of patients with PCP, multiple Pneumocystis strains can be identified using recently developed typing techniques. Because Pneumocystis cannot be cultured, diagnosis relies on detection of the organism by colorimetric or immunofluorescent stains or by polymerase chain reaction. Trimethoprim-sulfamethoxazole is the preferred drug regimen for both treatment and prevention of PCP, although a number of alternatives are also available. Corticosteroids are an important adjunct for hypoxemic patients.

Topics: Anti-Infective Agents; Antifungal Agents; Glucocorticoids; Humans; Immunocompromised Host; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Opportunistic Infections; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole may cause hyperkalaemia by the amiloride-like effect of trimethoprim on sodium channels in the distal nephron. Hyperkalaemia usually occurs after 7-10 days and has been reported in 20%-50% of patients receiving trimethoprim-sulfamethoxazole. Patients with Pneumocystis jiroveci pneumonia and severe hypoxaemia benefit from the use of prednisolone as an adjuvant to trimethoprim-sulfamethoxazole. The addition of prednisolone may lower the incidence of trimethoprim-related hyperkalaemia due, in part, to its mineralocorticoid activity. We studied the effect of concomitant prednisolone on trimethoprim-related hyperkalaemia.. Thirty patients qualified for inclusion and were reviewed. Patients were divided into two groups: one group received trimethoprim-sulfamethoxazole plus prednisolone (18 patients); and the other group received trimethoprim-sulfamethoxazole alone (12 patients).. The two groups were comparable at baseline, except for the severity of the P. jiroveci pneumonia. Hyperkalaemia developed in seven patients: all in the prednisolone and trimethoprim-sulfamethoxazole group. The greater incidence of hyperkalaemia in this group is surprising and was counter to our expectation.. Although it is possible that there is an unexplained interaction between trimethoprim and prednisolone, we postulate that our observation is a result of the catabolic effect of prednisolone. The patients treated with trimethoprim-sulfamethoxazole plus prednisolone appear to be more likely to develop hyperkalaemia than patients treated with trimethoprim-sulfamethoxazole alone.

Topics: Adult; Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Female; Humans; Hyperkalemia; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Desensitization, Immunologic; Drug Eruptions; HIV Infections; Humans; Male; Patch Tests; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A retrospective case-notes audit of 359 HIV-1-infected adult patients with first-episode laboratory-confirmed Pneumocystis jirovecii pneumonia treated with co-trimoxazole (from 1987 adjuvant steroids were used if PaO(2) <9.3 kPa) showed that only 230/359 (64%) patients completed treatment; 104 (29%) patients had treatment-limiting toxicity; rash occurred in 4/60 (6.7%) patients in 1985-1988 and in 15/47 (31.9%) in 2005-2008. Twenty-five patients (7%) failed co-trimoxazole treatment. Overall mortality was 13.6% (49/359); mortality among patients who failed co-trimoxazole treatment was 48% (12/25) and by contrast mortality was 4.8% (5/104) among patients with treatment-limiting toxicity.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia is common in immunocompromised individuals.. This case report describes an immunosuppressed patient who acquired P jiroveci pneumonia 6 months after renal transplant surgery.. The patient experienced many pneumonia-related complications and adverse effects from drug therapy, and despite treatment with various antibiotic agents, he died on the 62nd day after his admission to the intensive care unit.. The therapeutic failure of the drug of choice (co-trimoxazole) was evident. This case raises questions about the development of P jiroveci resistance to current therapies.

Topics: Adult; Anti-Infective Agents; Fatal Outcome; Humans; Immunocompromised Host; Kidney Transplantation; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Twenty patients with collagen diseases complicated with Pneumocystis pneumonia (PCP) were retrospectively examined in reference to the criteria for its protective therapy provided by the Ministry of Health Labor and Welfare. The breakdown of 20 patients was rheumatoid arthritis (RA) in 5 cases, systemic lupus erythematosus (SLE) in 5, dermatomyositis (DM) in 2, systemic scleroderma (SSc) in 1, mixed connective tissue disease (MCTD) in 1, Sjögren syndrome (SjS) in 1, polyarteritis nodosa (PN) in 3, rapidly progressive glomerulonephritis (RPGN) in 1, Schönlein-Henoch purpura in 1. Patients having interstitial pneumonia (IP) or renal dysfunction before acquiring PCP showed poor prognosis. High level of beta-D glucan was observed in all patients, and elevated levels of LDH and KL-6 were also characteristic of PCP. For the treatment of their own collagen diseases, high dose steroids had been given in 11 patients (55%), and immunosuppressive agents in 12 (60%), resulting in severe suppression of immune function in these patients. They were treated with Sulfamethoxazole/trimethoprim (ST) after Pneumocystis infection, however, 10 patients died and 8 of them died of respiratory failure in spite of high dose steroids. Nine patients fulfilled the criteria for PCP protective therapy provided by Ministry of Health Labor and Welfare, and 7 of them died of respiratory failure. The frequency of PCP remarkably decreased in our hospital after we had started the protective therapy with ST using the criteria, suggesting that it is effective for the protection of PCP. However, some patients who do not fulfill the criteria may acquire severe PCP.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Collagen Diseases; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients receiving intensive care. The double-sandwich ELISA for galactomannan is reported to have a high sensitivity (96.5%) for the detection of invasive aspergillosis when a cut-off value of 0.8 ng/ml is used. However, we have experienced a case of lethal disseminated aspergillosis in a patient that presented with a negative galactomannan (GM) test and persistent elevation of beta-D glucan (BG) levels. A 63-year-old female was admitted to our Intensive Care Unit (ICU) in acute respiratory failure and elevated BG. She had been receiving medication for Good-pasture syndrome based on anti-glomerular basement membrane antibodies and myeloperoxidase-antineutrophil cytoplasmic antibodies for 9 months and was receiving long-term prednisolone therapy (20 mg/day). On admission, her trachea was immediately intubated, and a PCR analysis of the bronchoalveolar lavage sample revealed Pneumocystis jiroveci. Trimethoprimsulfamethoxazole therapy was started for Pneumocystis pneumonia. The levels of BG remained elevated (> 100 pg/ml) during the treatment period despite the clinical resolution of Pneumocystis pneumonia, raising concerns of another complicated invasive fungal disease; consequently, fosfluconazole was administered empirically. The serum BG levels, however, did not decrease. Blood cultures did not detect a fungal infection. Serum GM levels measured by a double-sandwich ELISA on the 6th, 11th, and 24th days in the ICU were negative (< 0.2 ng/ml). The patient ultimately died of multiple organ failure on the 45th ICU day. Postmortem examination revealed a disseminated fungal infection with aggressive vascular invasion of the lungs, heart, and brain. In situ hybridization with a 568-bp probe of the alkaline proteinase sequence of Aspergillus fumigatus showed specific positive staining within the fungus present in the infected lung tissue, revealing that this patient may have had a systemic infection by A. fumigatus or A. flavus. This is a case of serum GM-negative disseminated aspergillosis pathologically proven by autopsy. Persistent elevated BG levels (> 100 pg/ml) refractory to trimethoprim-sulfamethoxazole and fosfluconazole may suggest possible Aspergillus infection and should prompt the initiation of empiric anti-aspergillosis therapies in patients at risk for fungal infection.

Topics: Antifungal Agents; Aspergillosis; Aspergillus; beta-Glucans; Brain; Fatal Outcome; Female; Galactose; Heart; Humans; Immunosuppressive Agents; Intensive Care Units; Lung; Mannans; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

There are limited data on the efficacy of alternative regimens for treating patients with pneumocystis pneumonia (PCP). We compared the efficacy of clindamycin-primaquine (C-P) with that of pentamidine as a second line treatment for PCP. Among 91 patients receiving trimethoprim-sulfamethoxazole (TMP-SMX) as a first-line treatment for PCP, 31 (34%) did not respond and 7 (8%) had adverse reactions. Fourteen patients received C-P and 9 received pentamidine as a second-line regimen because of treatment failure or an adverse reaction to TMP-SMX. The response rate of patients to C-P was higher than the response rate to pentamidine (9/14; 64% vs 1/9; 11%; P = 0.03).

Topics: Adult; Aged; Anti-Infective Agents; Clindamycin; Female; Humans; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

First-line therapy for Pneumocystis jirovecii pneumonia (PCP) is trimethoprim/sulfamethoxazole. Few data exist to guide the choice of second-line therapy for patients failing or developing toxicity to first-line therapy.. A case note review of 1122 patients with 1188 episodes of HIV-associated PCP from three observational cohorts in Copenhagen, London and Milan, between 1989 and 2004, was conducted.. Trimethoprim/sulfamethoxazole (962 PCP episodes, 81%) was the most frequently used first-line therapy, followed by intravenous pentamidine (87 episodes, 7%), clindamycin/primaquine (72 episodes, 6%) and 'other' (atovaquone, dapsone/pyrimethamine, trimetrexate or inhaled pentamidine; 67 episodes, 6%). Rates of unchanged therapy were trimethoprim/sulfamethoxazole = 79%, clindamycin/primaquine = 65% and pentamidine = 60% (P < 0.001). First-line therapy was changed because of failure in 82 (7%) episodes and because of toxicity in 198 (17%) episodes. Three month survival rates were trimethoprim/sulfamethoxazole = 85%, clindamycin/primaquine = 81% and pentamidine = 76% (P = 0.09). After adjustment for possible confounders, pentamidine was associated with a significantly greater risk of death at 3 months [hazard ratio (HR) = 2.0, 95% confidence interval (CI) = 1.2-3.4]. Second-line therapy survival rates differed: trimethoprim/sulfamethoxazole = 85%; clindamycin/primaquine = 87%; and pentamidine = 60% (P = 0.01). Multivariable time-updated Cox regression analysis showed a greater risk of death associated with pentamidine (HR = 3.3, 95% CI = 2.2-5.0), but not for clindamycin/primaquine, when both were compared with trimethoprim/sulfamethoxazole.. Pentamidine was associated with a greater risk of death when used as first- and second-line therapy for HIV-associated PCP, and was associated with more treatment changes. Clindamycin/primaquine appeared superior to pentamidine as second-line therapy for PCP in patients failing or developing toxicity with trimethoprim/sulfamethoxazole. In patients failing first-line treatment with non-trimethoprim/sulfamethoxazole regimens, second-line therapy should be trimethoprim/sulfamethoxazole.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Antifungal Agents; Clindamycin; Cohort Studies; Denmark; Female; Humans; Italy; London; Male; Middle Aged; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Primaquine; Survival Analysis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: 'When to start ART': Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. 'What to start with': A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained.

Topics: Adolescent; Adult; Age Factors; Anti-Infective Agents; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Child; Child, Preschool; Drug Resistance, Viral; Europe; Female; Hepatitis, Viral, Human; HIV Infections; HIV Long-Term Survivors; HIV-1; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Patient Education as Topic; Pneumonia, Pneumocystis; Pregnancy; Randomized Controlled Trials as Topic; RNA, Viral; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult

Pneumocystis jirovecii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients is usually treated with trimethoprim (TMP)-sulfamethoxazole (SMX) 1920 mg 3 times daily (approximately equivalent to TMP 15 mg/kg/day-SMX 75 mg/kg/day) for 21 days. Pharmacokinetic data suggest that lower doses would be equally efficacious and might be associated with a lower incidence of adverse effects. We conducted a retrospective review of case notes for the first episode of laboratory-confirmed PCP in HIV-infected patients treated at Auckland City Hospital, from January 1991 through December 2007. Seventy-three of 84 (87%) patients were treated with TMP-SMX 960 mg 4 times daily or 3 times daily (approximately TMP 10 mg/kg/day-SMX 50 mg/kg/day). The overall mortality was 5/73 (7%). The mortality in patients with severe disease (transcutaneous oxygen saturation on admission < or =84%) was 3/16 (19%) and in patients admitted to the intensive care unit was 5/9 (56%). Fifteen of 73 (21%) patients required a change to an alternative treatment regimen because of adverse effects (rash in 10, rash plus fever in 3, neutropenia in 1, fever plus headache in 1). Treatment of PCP in adult HIV-infected patients with TMP-SMX 960 mg QID or TID appears to have comparable efficacy to treatment with higher doses and to be associated with a lower rate of treatment limiting adverse effects.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; HIV Infections; Humans; Logistic Models; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Sulfamethoxazole; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

A 23-year-old Japanese woman was diagnosed with lupus nephritis on May 2007. The patient was prescribed 30 mg/day of prednisolone, but developed a pulmonary abscess and was admitted to Sapporo Medical University Hospital in March 2008. Antibiotics improved the symptoms. We prescribed trimethoprim-sulfamethoxazole as prophylaxis for pneumocystis pneumonia; however, the patient developed fever and thrombocytopenia with hyperferritinemia after a week of this prophylaxis. We considered that she was developing hemophagocytic syndrome, and administered methylprednisolone pulse therapy. The clinical findings soon improved. However, when the prophylaxis was restarted, the patient developed fever, headache, and anaphylaxis the same day. Symptomatic therapy resolved these symptoms after three days, but they recurred on recommencing trimethoprim-sulfamethoxazole. Analysis of the cerebrospinal fluid revealed aseptic meningitis. These episodes were thought to be induced by trimethoprim-sulfamethoxazole. As trimethoprim-sulfamethoxazole is frequently used as prophylaxis for pneumocystis infection in immunosuppressed patients, clinicians should be vigilant regarding the complications of this treatment, particularly the rare occurrence of aseptic meningitis and anaphylaxis.

Topics: Anaphylaxis; Anti-Infective Agents; Antibiotic Prophylaxis; Female; Humans; Immunocompromised Host; Lupus Nephritis; Meningitis, Aseptic; Pneumonia, Pneumocystis; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Anti-Infective Agents; Drug Design; Graft vs Host Disease; Hematopoietic Stem Cells; Humans; Organ Transplantation; Pneumonia, Pneumocystis; Stem Cell Transplantation; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

The incidence of pneumonia caused by Pneumocystis carinii (PCP) (organism now renamed Pneumocystis jiroveci) during the early period after cord blood transplantation (CBT) was studied in 120 adults. Initially 89 patients (74%) received oral administration of 2 single-strength trimethoprim-sulfamethoxazole (TMP-SMZ) tablets twice daily from day -21. In 45 of 89 patients (51%), TMP-SMZ administration for a scheduled duration was completed. In the remaining 44 patients (49%), however, TMP-SMZ administration was discontinued prior to day -3 because of toxicity. Among these patients, 42 subsequently received aerosolized pentamidine (AP) on a median of day -13 (range, -20 to -6). Thirty-one patients (26%) received AP without TMP-SMZ administration on a median of day -14 (range, -21 to -9). None of the 120 patients were diagnosed with PCP within 100 days or 2 years after CBT; however, one patient who received AP before CBT but no prophylaxis after CBT developed cerebral toxoplasmosis on day +91. Pre-transplant prophylaxis against PCP did not significantly affect transplantation-related mortality or disease-free survival at 2 years after CBT. The results suggest that PCP during the early period after CBT can be effectively prevented by any pre-transplant prophylactic method.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Antifungal Agents; Cord Blood Stem Cell Transplantation; Drug Administration Schedule; Female; Hematologic Diseases; Humans; Incidence; Male; Middle Aged; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Tokyo; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

A 22-year-old man was admitted to our hospital with fever, cough and dyspnea. His chest radiograph showed diffuse ground-glass attenuation in both lung fields. Arterial blood gas analysis showed hypoxemia (PaO2 28.7 Torr breathing room air) and he required mechanical ventilation within 6 hours after admission. Gomori methenamine silver (GMS) stain of the bronchoalveolar lavage (BAL) fluid smear showed round and indented organisms, and polymerase chain reaction revealed pneumocystis jirovecii in the BAL fluid. The HIV antibody was positive and peripheral blood CD4-positive lymphocytes decreased to 4.0%. Pneumocystis pneumonia complicated with acquired immunodeficiency syndrome (AIDS) was diagnosed. There was no four-fold rise in screen viral titers. We treated him with antibiotics, trimethoprim-sulfamethoxazole, ganciclovir, fos-fluconazole, steroid pulse therapy and sivelestat sodium hydrate. Respiratory failure was relieved within 5 days following treatment. The percentage of neutrophils in the BAL fluid was elevated (44.6%). Neutrophil elastase on admission was increased and improved to the normal range after treatment. Sivelestat sodium hydrate is an anti-neutrophil elastase inhibitor and may be one of the treatment options for acute respiratory failure due to pneumocystis pneumonia in AIDS patients.

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Adult; Drug Therapy, Combination; Ganciclovir; Glycine; Humans; Male; Methylprednisolone; Pneumonia, Pneumocystis; Proteinase Inhibitory Proteins, Secretory; Pulse Therapy, Drug; Respiratory Insufficiency; Severity of Illness Index; Sulfonamides; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Symptomatic primary HIV infection occurs in an estimated 50% to 90% of patients. A constellation of symptoms that most closely resembles those of acute infectious mononucleosis characterizes the syndrome. On rare occasions, opportunistic infections present simultaneously with primary HIV infection. We describe a patient who presented with an episode of severe Pneumocystis jiroveci pneumonia during what appeared to be a prolonged primary HIV infection. Serological testing demonstrated the progressive development of reactive bands on serial Western blot determinations. This case highlights how primary HIV infection can produce profound immunosuppression through CD4 lymphocytopenia predisposing patients to opportunistic infection.

Topics: Adult; AIDS-Related Opportunistic Infections; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci (PJ) infection is rare in infants and is suggestive of primary or secondary immunodeficiency. We report on a case of severe PJ pneumonia in an immunocompetent infant after prolonged corticosteroid treatment.. A 5 1/2 month-old girl presented with hypoxemic respiratory distress. Her medical record was remarkable only for a bulky parotid haemangioma, which was treated with prolonged oral corticosteroid therapy. The chest X-ray showed a mixed alveolar-interstitial pattern, and bronchoalveolar lavage revealed the presence of PJ. A favourable outcome was obtained after three weeks of intravenous trimethoprim-sulfamethoxazole treatment.. PJ infection should be suspected in infants presenting with progressive respiratory distress associated with a mixed alveolar-interstitial pattern. Its potential seriousness justifies prophylactic therapy during prolonged immunosuppressive treatment (chemotherapy, corticosteroid treatment).

Topics: Administration, Oral; Anti-Infective Agents; Anti-Inflammatory Agents; Betamethasone; Bronchoalveolar Lavage; Female; Glucocorticoids; Hemangioma; Humans; Infant; Parotid Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography, Thoracic; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Female; HIV Infections; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia is an opportunistic infection capable of causing life-threatening pneumonia in immunocompromised patients. To elucidate the clinical presentation and outcome of this disease in Taiwan, we analyzed the patients with P. jirovecii pneumonia during a 34-month period.. We collected data retrospectively from patients with P. jirovecii pneumonia at a medical center in northern Taiwan between January 2004 and October 2006. The diagnosis was made by nested polymerase chain reaction (PCR) analysis of expectorated sputum. Demographics, clinical characteristics, laboratory findings, and outcomes were compared between patients with and without human immunodeficiency virus (HIV) infection.. Forty nine patients were included in this study. The most common underlying diseases were HIV and malignancies. The mean (+/- standard deviation) age of the 49 patients was 54 +/- 20.2 years (range, 5 to 96 years). The mean CD4+ T-lymphocyte count was 110 cells/microL (range, 0-670 cells/microL). Although the mean CD4+ T-lymphocyte count of the non-HIV group was higher than that of the HIV group (165 +/- 78 cells/microL vs 57.5 +/- 97 cells/microL), statistical significance was not obtained (p=0.087). Arterial oxygenation (ratio of arterial oxygenation to fraction of inspired oxygen) was less than 200 mm Hg in 28 patients. Lactate dehydrogenase levels were higher than the normal range in 15 patients. A significantly higher proportion of patients died in the group without HIV compared with the HIV-infected patients (17/34 [50.0%] vs 1/15 [6.7%]; p=0.004).. P. jirovecii pneumonia remains a significant problem for immunocompromised patients. The mortality rate for patients without HIV infection was high (50%). Greater alertness with regard to early detection of P. jirovecii in HIV-negative immunosuppressed patients with the application of nested PCR may improve the clinical management and outcome.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Analysis of Variance; Anti-Infective Agents; Chi-Square Distribution; Child; Child, Preschool; Female; HIV Infections; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Retrospective Studies; Sputum; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is a serious complication of chemotherapy-induced immunosuppression. Trimethoprim-sulfamethoxazole (TMP-SMZ) given twice daily, 3 days every week is considered the best form of prophylaxis for PCP. We evaluated PCP prophylaxis in all children up to 18 years of age undergoing cancer chemotherapy over a 2-year period. Four children were diagnosed with PCP over 24 months. Two of 12 children on intravenous pentamidine, 1 of 143 on TMP-SMZ and 1 of 36 on dapsone for PCP prophylaxis developed PCP. Intravenous pentamidine may not be as effective as previously considered and should be used with caution.

Topics: Adolescent; Adult; Anti-Infective Agents; Antibiotic Prophylaxis; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Immunocompromised Host; Infant; Infusions, Intravenous; Male; Neoplasms; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii, formerly carinii, pneumonia (PCP) poses a life-threatening risk to oncology patients. The use of trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis virtually eliminates the risk of infection; however, many patients cannot tolerate TMP-SMZ. We performed a retrospective analysis to determine the PCP breakthrough rate in pediatric oncology patients receiving intravenous pentamidine as second line PCP prophylaxis.. We conducted a retrospective chart review of pediatric oncology patients who received intravenous pentamidine from 2001 to 2006 at our institution. The diagnosis, age and bone marrow transplant (BMT) status were determined. A subset of patients had review of their records to determine the justification for discontinuing TMP-SMZ. Children who developed symptoms of pneumonia with a clinical suspicion of PCP underwent bronchoscopy, allowing for identification of Pneumocystis.. A total of 232 patients received 1,706 doses of intravenous pentamidine and no toxicities were identified. The main reasons for discontinuing TMP-SMZ were bone marrow suppression and drug allergy. Three children developed PCP, equating to a breakthrough rate of 1.3%. Two of these children had undergone BMT (1.9% breakthrough rate) and both were under the age of two (6.5% breakthrough rate).. The use of intravenous pentamidine as PCP prophylaxis results in a breakthrough rate of 1.3%. TMP-SMZ is the first choice for PCP prophylaxis. However, when necessary, the use of intravenous pentamidine has an acceptably low failure rate, even in high-risk BMT patients. Other options should be considered for children less than 2 years of age.

Topics: Antifungal Agents; Bone Marrow Transplantation; Child; Child, Preschool; Humans; Immunocompromised Host; Infant; Injections, Intravenous; Neoplasms; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, B-Cell; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

To evaluate the efficacy of primary prophylaxis for Pneumocystis jiroveci pneumonia (PCP) in patients with connective tissue disease (CTD) and immunosuppression, we compared trimethoprim-sulfamethoxazole (TMP-SMZ) with aerosolized pentamidine. Forty-eight CTD patients of Kitasato University Hospital whose CD4+ lymphocyte count in the peripheral blood was less than 300 microl(-1) were reviewed from 2002 to 2004. Twenty-seven patients received TMP-SMZ and none of them developed PCP. Among 18 patients receiving aerosolized pentamidine, three patients developed PCP. These data indicate that TMP-SMZ is better for prophylaxis than aerosolized pentamidine.

Topics: Adult; Aerosols; Aged; CD4 Lymphocyte Count; Connective Tissue Diseases; Female; Humans; Immunocompromised Host; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia (PCP) is a potentially fatal complication in interstitial pneumonia patients receiving glucocorticoid therapy. Prophylaxis of PCP during glucocorticoid therapy is an important issue in the treatment of interstitial pneumonia.. We evaluated the prophylactic effect of sulfamethoxasole-trimethoprim (TMP-SMX) in interstitial pneumonia patients receiving glucocorticoids.. We retrospectively analyzed 74 interstitial pneumonia patients who received glucocorticoid therapy.. Seven of the 74 patients developed PCP. At the time of diagnosis of PCP, the mean duration of glucocorticoid therapy was 71 days and the mean daily dose of prednisolone was 37 mg. Among the 7 patients, the circulating CD4+ lymphocyte count was 370 /microl on average and it was over 200 /microl in 3 cases. The PCP patients showed a significant reduction of the lymphocyte count at 4 weeks after initiation of steroid therapy. None of the patients who received prophylactic TMP-SMX therapy developed PCP even if the CD4+ lymphocyte count was less than 200 /microl.. Interstitial pneumonia patients receiving glucocorticoid therapy can benefit from TMP-SMX prophylaxis against PCP. Development of PCP cannot be ruled out in patients with a CD4+ lymphocyte count of greater than 200 /microl.

Topics: Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Antibiotic Prophylaxis; CD4 Lymphocyte Count; Female; Glucocorticoids; Humans; Lung Diseases, Interstitial; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisolone; Radiography; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We report a patient who presented 6 months after orthotopic liver transplantation (OLT) with fever, dyspnea, and pulmonary infiltrates with biopsy-confirmed Pneumocystis jiroveci infection associated with a process of bronchiolitis obliterans organizing pneumonia (BOOP). We present this second case of BOOP associated with P. carinii pneumonia after OLT to highlight the risk of such disease combination in all transplant patients as well as discuss the protective effect of post-transplant prednisolone with trimethoprim-sulfamethoxazole prophylaxis and the possible duration of prophylaxis.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Biopsy; Cryptogenic Organizing Pneumonia; Diagnosis, Differential; Drug Therapy, Combination; Hepatitis, Alcoholic; Humans; Liver Transplantation; Lung; Male; Middle Aged; Pneumocystis carinii; Pneumonia; Pneumonia, Pneumocystis; Prednisolone; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Inflammatory Agents; Antiretroviral Therapy, Highly Active; Hodgkin Disease; Humans; Immune Reconstitution Inflammatory Syndrome; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Eye Infections, Fungal; Fluorescein Angiography; Humans; Male; Pneumonia, Pneumocystis; Retinal Vein Occlusion; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Belgium; Contraindications; Databases, Factual; Drug Interactions; Female; Humans; Medication Errors; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Although co-trimoxazole (trimethoprim-sulphamethoxazole) is an effective drug for prophylaxis against and treatment of Pneumocystis pneumonia, patients often experience adverse events with this combination, even at prophylactic doses. With the aim being to achieve individual optimization of co-trimoxazole therapy in patients with systemic lupus erythematosus (SLE), we investigated genetic polymorphisms in the NAT2 gene (which encodes the metabolizing enzyme of sulphamethoxazole). Of 166 patients with SLE, 54 patients who were hospitalized and who received prophylactic doses of co-trimoxazole were included in the cohort study. Adverse events occurred in 18 patients; only two experienced severe adverse events that lead to discontinuation of the drug. These two patients and three additional ones with severe adverse events (from other institutions) were added to form a cohort sample and were analyzed in a case-control study. Genotype was determined using TaqMan methods, and haplotype was inferred using the maximum-likelihood method. In the cohort study, adverse events occurred more frequently in those without the NAT2*4 haplotype (5/7 [71.4%]) than in those with at least one NAT2*4 haplotype (13/47 [27.7%]; P = 0.034; relative risk = 2.58, 95% confidence interval = 1.34-4.99). In the case-control study the proportion of patients without NAT2*4 was significantly higher among those with severe adverse events (3/5 [60%]) than those without severe adverse events (6/52 [11.5%]; P = 0.024; odds ratio = 11.5, 95% confidence interval = 1.59-73.39). We conclude that lack of NAT2*4 haplotype is associated with adverse events with co-trimoxazole in Japanese patients with SLE.

Topics: Alanine Transaminase; Anti-Infective Agents; Arylamine N-Acetyltransferase; Asian People; Aspartate Aminotransferases; Case-Control Studies; Cohort Studies; Haplotypes; Humans; Immunocompromised Host; Lupus Erythematosus, Systemic; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia is a classic opportunist infection affecting AIDS patients. However it is less frequent since systematic prophylaxis and antiretroviral therapies. Treatment resistance is rare in France. We report the case of a severe Pneumocystis jiroveci pneumonia with treatment resistance to standard treatment and fatal outcome. The different causes of treatment resistance, notably the role of CMV co-infection, were reviewed and discussed.

Topics: Anti-Infective Agents; Cytomegalovirus Infections; Drug Resistance, Bacterial; Fatal Outcome; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Two Pneumocystis jiroveci independent genomic regions, internal transcribed spacer (ITS) 1 and ITS2, and dihydropteroate synthase (DHPS) gene have been used for typing a cohort of HIV-infected Italian patients with P jiroveci pneumonia (PcP).. Bronchoalveolar lavage samples isolated from 207 HIV-infected adults were ITS and DHPS genotyped by DNA sequencing and by restriction fragment length polymorphism analysis, respectively. Mutant DHPS samples were cloned and ITS typed. Data on severity, treatment, and outcome of PcP were obtained by chart review.. High diversity with 46 different ITS genotypes was observed. At the DHPS locus, 9.1% of samples analyzed were found to be mutated. A correlation was observed between DHPS mutants and greater severity of PcP, as defined by higher lactate dehydrogenase (P = 0.015) and need for intubation (P = 0.002), and worse outcomes, as defined by failure of sulfa treatment (P = 0.04), death, and/or relapse of PcP (P = 0.008). There was a significant difference in ITS genotype patterns between DHPS wild-type and mutants (P = 0.028).. The present data suggest the absence of a correlation between P jiroveci ITS types and specific clinical characteristics. DHPS mutations correlate with possible failure of anti-P jiroveci sulfa therapy, and a trend of association is shown between DHPS mutations and some clinical PcP features.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Dihydropteroate Synthase; Disease Progression; DNA, Intergenic; Female; Genes, Viral; HIV; Humans; Italy; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Polymorphism, Genetic; Species Specificity; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Proteins

This study was conducted to determine the efficacy of dosing trimethoprim/sulfamethoxazole on 2 consecutive days per week for the prevention of Pneumocystis carinii (jiroveci) pneumonia in a pediatric leukemia and lymphoma population and to determine whether trimethoprim/sulfamethoxazole contributes to neutropenia during maintenance therapy.. Charts were reviewed for all pediatric patients with leukemia and lymphoma diagnosed between January 1, 1993, and December 31, 2002. Data were collected through April 1, 2004.. A total of 575 charts were reviewed; 529 patients were included in the analysis. A total of 482 (345 leukemia, 137 lymphoma) patients were evaluated on trimethoprim/sulfamethoxazole dosed 2 consecutive days per week for 268074 patient-days. No breakthrough cases were documented in compliant patients; 2 noncompliant patients developed P. carinii pneumonia. A total of 238 patients who were on trimethoprim/sulfamethoxazole prophylaxis and 13 patients who were receiving an alternative medication prophylaxis were evaluated for neutropenia during maintenance therapy. The median number of maintenance days on trimethoprim/sulfamethoxazole was 605.5 days and on alternative drug was 617 days. The median number of neutropenic maintenance days on trimethoprim/sulfamethoxazole was 15.5 days and on the alternative drug was 16 days. The median proportion of neutropenic days per patient was 0.029 on trimethoprim/sulfamethoxazole and 0.022 on the alternative drug.. Intermittent dosing of trimethoprim/sulfamethoxazole on 2 consecutive days per week is an effective alternative prophylactic regimen for P. carinii pneumonia in pediatric patients with leukemia and lymphoma. This analysis does not support a difference in neutropenia during maintenance therapy between patients who are treated with trimethoprim/sulfamethoxazole versus an alternative drug.

Topics: Anti-Infective Agents; Child; Drug Administration Schedule; Humans; Leukemia; Lymphoma; Neutropenia; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A 76-year-old man, who was in the hospital for the treatment of type 2 diabetes mellitus and was receiving gonadotropin-releasing hormone (GnRH) agonist treatment for prostate cancer, developed fever and hypoxemia. Imaging revealed diffuse interstitial shadows, and PCR of the bronchoalveolar lavage fluid was positive for Pneumocystis jirovecii. The patient's absolute CD4-positive lymphocyte count dropped to 145/microl, but the HIV antibody was negative. After trimethoprim-sulfamethoxazole (TMP/SXT) treatment, the absolute CD4 positive lymphocyte count returned to normal. This patient with type 2 diabetes mellitus developed Pneumocystis pneumonia and developed a transient decrease in CD4-positive lymphocytes.

Topics: Aged; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; CD4 Lymphocyte Count; Diabetes Mellitus, Type 2; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To examine sICAM-1 in Pneumocystis carinii pneumonia (PCP) and the effect of TMP-SMZ therapy on its level and on pathological and immunological changes in rats.. 50 female Wistar rats were randomly divided into normal group (N group), PCP model group (PCP group) and TMP-SMZ therapy group (SMZ group). 1 mg of dexamethasone was injected intramuscularly twice a week for rats in PCP and SMZ groups to induce PCP. Normal saline was injected for N group in the same way. When the infection was confirmed, TMP-SMZ was given to rats in SMZ group by 25 mg/(kg.d) for 5 days for 3 courses with an interval of 2 weeks. sICAM-1 in serum was detected by ELISA, and the pathological changes in lungs and liver and the Pc in alveoli of lungs were observed.. The level of sICAM-1 in PCP and SMZ groups at the 3rd week [(1.847+/-0.50) ng/ml, (1.787+/-0.59) ng/ml] was lower notably than that at 0 week [(2.407+/-0.81) ng/ml, [(2.478+/-0.59) ng/ml respectively] (P<0.05), and then increased gradually. It was significantly higher in PCP group at 9th week [(3.233+/-0.83) ng/ml] and at 12th week [(3.984+/-0.87) ng/ml] than that of 0 week (P<0.05). Its level in SMZ group at 12th week [(3.621+/-l.62) ng/ml] was also higher than that in 0 week [(2.478+/-0.59) ng/ml] (P<0.05). sICAM-1 level in both PCP and SMZ groups at 9th week and 12th week was higher than that of N group (P<0.05, P<0.01). There was no significant difference between SMZ and PCP groups at 9th week and 12th week (P>0.05).. The sICAM-1 level in rats was low but significantly increases after the induction of PCP.

Topics: Animals; Enzyme-Linked Immunosorbent Assay; Female; Host-Pathogen Interactions; Intercellular Adhesion Molecule-1; Pneumocystis carinii; Pneumonia, Pneumocystis; Random Allocation; Rats; Rats, Wistar; Solubility; Trimethoprim, Sulfamethoxazole Drug Combination

We report an unusual case of nephrotic syndrome due to membranous glomerulonephritis that responded to high-dose trimethoprim-sulfamethoxazole (TMP-SMX) treatment. A 52-year-old man presented with nephrotic syndrome and was diagnosed to have idiopathic membranous glomerulonephritis. At the time of diagnosis, his serum creatinine level was 1.2 mg/dl and daily urine protein excretion was 7.45 g. The patient was initially treated with angiotensin-converting enzyme inhibitor and diuretics. After a 6-month period, the patient remained symptomatic. Therefore, immunosuppressive therapy with a 6-month course of alternating corticosteroids with cyclophosphamide was commenced. Unfortunately, as a sequel of the immunocompromised state, the patient acquired severe pneumonia due to Pneumocystis jiroveci infection when he was on the fourth month of immunosuppressive therapy. At this time, he still had nephrotic range proteinuria and hypoalbuminemia. Because of the risk of aggravating infection, immunosuppressive agents were discontinued. A 14-day course of intravenous high-dose TMP-SMX therapy was given for the treatment of Pneumocystis jiroveci pneumonia. With this medication, not only the pneumonia was cured, but also a sustained remission of the nephrotic syndrome occurred. This case suggests a possible therapeutic role of high-dose TMP-SMX in membranous glomerulonephritis. We will discuss the possible mechanism.

Topics: Anti-Infective Agents; Glomerulonephritis, Membranous; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Remission Induction; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia may be a life-threatening opportunistic infection in immunosuppressed solid organ transplant recipients. Despite effective treatment with high-dose trimethoprim-sulfamethoxazole and steroids, morbidity is often severe and lethality remains high. New therapeutic approaches are therefore warranted. Caspofungin, a beta-1,3-glucan synthesis inhibitor, has shown activity against the cyst forms of P. jiroveci in experimental animal models. We here report our preliminary clinical experience with caspofungin as an additional drug to the standard trimethoprim-sulfamethoxazole regimen.. Four solid organ transplant patients with severe hypoxemic P. jiroveci pneumonia were treated with the combination of trimethoprim-sulfametoxazole and caspofungin. In two cases, caspofungin was added as salvage treatment due to failure of trimethoprim-sulfametoxazole monotherapy.. In these four patients, the use of caspofungin as an additional drug to the standard trimethoprim-sulfamethoxazole regimen led to a rapid improvement and a complete cure of pneumonia. No side effects or drug interactions were observed.. This preliminary clinical experience suggests that the addition of caspofungin to trimethoprim-sulfamethoxazole, which is active against trophic forms, may provide a synergistic activity against P. jiroveci by fully inhibiting the organism life cycle.

Topics: Adult; Anti-Infective Agents; Caspofungin; Drug Therapy, Combination; Echinocandins; Female; Humans; Immunosuppression Therapy; Lipopeptides; Male; Middle Aged; Organ Transplantation; Peptides, Cyclic; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) is a rare form of pneumonia associated with immune-suppression. It is common in patients with AIDS and with a CD4 count of less than 200 cells/mm(3). We report a case of PCP secondary to immune-suppression in a 41-year-old man with psoriatic arthritis being treated with the immune-modulatory agent etanercept.. Diagnosis of PCP was made histologically using tissue obtained via transbronchial biopsy.. There was a good response to standard treatment with high-dose co-trimoxazole.. This report highlights a recognised but previously unreported complication of etanercept.

Topics: Adult; Arthritis, Psoriatic; Biopsy, Needle; Etanercept; Follow-Up Studies; Humans; Immunoglobulin G; Immunohistochemistry; Immunosuppression Therapy; Immunosuppressive Agents; Male; Pneumonia, Pneumocystis; Receptors, Tumor Necrosis Factor; Risk Assessment; Severity of Illness Index; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To determine whether Malawi antiretroviral treatment (ART) clinics providing cotrimoxazole (CTX) prophylaxis had lower early mortality rates compared with clinics not providing CTX.. Retrospective cohort study of eleven ART clinics in Malawi that were or were not providing CTX. Medical record abstraction was performed for all patients (N = 1295) initiating ART between July 1 and December 15, 2005. At 5 ART sites, CTX was given to patients dosed at 960 mg daily or 480 mg twice a day (according to national guidelines).. When all defaults (patients lost to follow-up for >90 days) were excluded from the analysis, the 6-month mortality rate was 10.7% in patients receiving ART at CTX clinics compared with 18.0% in those not at CTX clinics (6-month mortality risk reduction = 40.7%; P = 0.0013). Kaplan-Meier survival curves for patients receiving CTX and patients not receiving CTX were significantly different; survival differences were apparent as early as 40 to 45 days after initiation of ART.. Patients receiving ART in Malawi at clinics offering CTX prophylaxis had significantly reduced mortality during the first 6 months of ART. This additional intervention may have the potential to improve the lives of patients on ART, because CTX is readily available and relatively inexpensive and can, in principle, be easily introduced into ART delivery programs.

Topics: Adolescent; Adult; Aged; Anti-HIV Agents; Cohort Studies; Dose-Response Relationship, Drug; Female; HIV Infections; Humans; Malawi; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bronchoscopy; CD4 Lymphocyte Count; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Hypoxia; Middle Aged; Oxygen Inhalation Therapy; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Radiography, Thoracic; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Antifungal Agents; Bone Marrow Transplantation; Caspofungin; Contraindications; Echinocandins; Humans; Leukemia, Lymphoid; Lipopeptides; Male; Middle Aged; Peptides, Cyclic; Pneumonia, Pneumocystis; Positron-Emission Tomography; Tomography, X-Ray Computed; Transplantation Conditioning; Trimethoprim, Sulfamethoxazole Drug Combination

A retrospective review was performed of patients diagnosed with Pneumocystis carinii pneumonia (PCP) from 1994 to 2003 at the Prince of Wales Hospital in Hong Kong. Eighteen patients were identified. Six (33.3%) were co-infected with human immunodeficiency virus (HIV). The remaining 12 non-HIV-infected patients had underlying diseases: three post-renal transplant recipients, three with haematological malignancies, two with auto-immune diseases, two with renal diseases, one with hepatocellular carcinoma and one with congenital cytomegalovirus disease. Cytomegalovirus co-infection was observed in four patients. All patients received cotrimoxazole therapy, with intolerance observed in four of them, including one with glucose-6-phosphate dehydrogenase deficiency, two with repeated vomiting and one with renal impairment. Overall crude mortality was 33.3%. The results suggested that, apart from being a common infection for patients with HIV infection, PCP can occur during the course of many immunosuppressive diseases and therapies. The mortality of PCP was high despite appropriate treatment. Chemoprophylaxis should be considered in populations at risk.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Child; Child, Preschool; Female; HIV Infections; Hong Kong; Humans; Immunocompromised Host; Infant; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Codon; Dihydropteroate Synthase; DNA, Fungal; Drug Resistance, Fungal; Germany; HIV Infections; Humans; Immunocompromised Host; Lymphoma, T-Cell; Pneumocystis carinii; Pneumonia, Pneumocystis; Point Mutation; Trimethoprim, Sulfamethoxazole Drug Combination

We have previously shown that zidovudine plus sulfamethoxazole-trimethoprim exposure decreases immune cell populations in the bone marrow of healthy mice by inducing apoptosis. The hypothesis of the current work was that this toxicity would have an adverse impact on the immune response. To determine this, BALB/c mice were treated with zidovudine, sulfamethoxazole-trimethoprim, the combination of both drugs, or vehicle only (control) via oral gavage for 21 days. On day 4 after dosing completion, the mice were infected intratracheally with 1x10(7) Pneumocystis murina organisms. Immune cell populations (in lung digest, bronchoalveolar lavage fluid, tracheobronchial lymph node, and bone marrow samples), the lung Pneumocystis burden, and serum Pneumocystis-specific antibody titers were determined at days 6, 10, and 20 postinfection. While total bone marrow cellularity was recovered by day 6 postinfection in the combination exposure group, B-cell numbers did not recover until 10 days postinfection, primarily due to the persistent depletion of the late pre-B-cell phenotype. The numbers of CD4+ and CD8+ T cells, as well as the numbers of total B cells and activated B cells in tracheobronchial lymph nodes, were decreased at days 10 and 20 as a result of zidovudine plus sulfamethoxazole-trimethoprim exposure compared to the numbers in the control group. No significant differences in lung lavage or lung digest cell populations were observed. There was a trend of a delay in Pneumocystis clearance in the combination treatment group, and Pneumocystis-specific serum immunoglobulin G titers were reduced at day 20 postinfection. Together, these data indicate that the combination of zidovudine and sulfamethoxazole-trimethoprim adversely affects the humoral immune response to Pneumocystis.

Topics: Animals; Antibodies, Fungal; B-Lymphocytes; Bone Marrow; Drug Interactions; Immune Tolerance; Immunoglobulin G; Lung; Mice; Mice, Inbred BALB C; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Co-trimoxazole (trimethoprim-sulfamethoxazole) is a commonly prescribed antimicrobial agent. Although it is well tolerated in most patients, serious adverse events related to its use have been described. Hypoglycaemia is a rare but potentially life-threatening complication of therapy. We describe a case of refractory hypoglycaemia complicated by seizure associated with co-trimoxazole for the treatment of Pneumocystis carinii pneumonia in a patient with AIDS. We also review 13 previously reported cases of co-trimoxazole-induced hypoglycaemia. Among this patient population, renal insufficiency was the most prevalent predisposing risk factor (93%). The mean daily dose of co-trimoxazole was 4.5 double strength (160 mg trimethoprim/800 mg sulfamethoxazole) tablets per day. Serum insulin levels were raised or inappropriately normal in 88% of cases in which they were measured, suggesting a sulfonylurea-like effect of co-trimoxazole as the mechanism of hypoglycaemia. All cases required intravenous glucose administration, and 43% experienced protracted (>12 hours) hypoglycaemia. Dosage adjustments should be made when prescribing co-trimoxazole to patients with renal dysfunction.

Topics: Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Antifungal Agents; Female; Glucose; Humans; Hypoglycemia; Infant; Insulin; Male; Middle Aged; Pneumonia, Pneumocystis; Risk Factors; Seizures; Trimethoprim, Sulfamethoxazole Drug Combination

We report that a-63-year-old woman developed Pneumocystis jiroveci pneumonia (PCP) as a complication from treatment with infliximab for rheumatoid arthritis. Although there was neither symptoms of dyspnea nor typical observations on a chest X-ray examination, low levels of oxygen saturation and findings of high-resolution chest computed tomographic scanning suggested a possibility of interstitial pneumonia. A polymerase chain reaction-based detection of Pneumocystis jiroveci in induced sputum allowed an early diagnosis of PCP and subsequent effective treatment.

Topics: Anti-Infective Agents; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Rheumatoid; Blood Gas Monitoring, Transcutaneous; Female; Humans; Immunocompromised Host; Infliximab; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

Pneumocystis carinii pneumonia (PCP) is a life-threatening opportunistic infection that occurs in immunocompromised hosts, especially patients with the acquired immunodeficiency syndrome (AIDS). However, this infection is increasing in frequency in other immunosuppressed patients, including organ transplant recipients and those with malignancy who are treated with chemotherapeutic regimens. It carries a relatively high mortality in the non-human immunodeficiency virus (HIV) population. Pleural involvement is rare with PCP; all reported cases in the literature are associated with HIV disease and characterized as small effusions. We report a case of a renal transplant recipient with PCP and moderate-sized pleural effusion with pneumocystis cysts.

Topics: Adult; Anti-Infective Agents; Diagnosis, Differential; Female; Humans; Immunocompromised Host; Kidney Transplantation; Pleural Effusion; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Although the association of Pneumocystis carinii pneumonia (PCP) with connective tissue disease (CTD) has been noted for a long time, there are few series reported.. The objective of this study was to describe clinical features and prognosis of PCP infections in patients with CTD in China.. We retrospectively reviewed the characteristics, clinical features, and prognosis of PCP in patients with CTD in a single hospital.. A total of 7 cases were reviewed (systemic lupus erythematosus n = 2, microscopic polyangiitis n = 2, dermatomyositis n = 2, polymyositis n = 1). Eighty-six percent of patients developed PCP within 3 months of the diagnosis of CTD. All patients were receiving daily glucocorticoid therapy and cytotoxic drugs before the diagnosis of PCP. Most patients had fever, progressive dyspnea, and dry cough at onset of PCP. The mean duration of symptoms before PCP diagnosis was 7 days. Absolute lymphocyte counts ranged from 126 to 528/microL. The CD4 lymphocyte counts of all patients were 87 +/- 78/microL. One patient was diagnosed by induced sputum; 6 patients were diagnosed by bronchoalveolar lavage fluid. Complicating fungal infection was found in 4 of 7 patients at the time of diagnosis of PCP. All patients were treated by trimethoprim-sulfamethoxazole and corticosteroids. Six (86%) patients died. The mean duration of the time from diagnosis to death was 14 +/- 4 days.. Our results suggest that PCP is an uncommon and fatal opportunistic infection in patients with CTD. When patients with CTD who are receiving immunosuppressive therapy have low lymphocyte counts and/or CD4 lymphocyte counts less than 250/microL develop fever, dry cough, dyspnea, and chest radiography shows diffuse interstitial infiltrate, the diagnosis of PCP should be highly suspected. Induced sputum or BAL must be quickly performed to confirm diagnosis. Further study is needed as to whether earlier treatment will improve prognoses or whether patients with CTD with low CD4 counts should receive PCP prophylaxis.

Topics: Adult; Aged; Connective Tissue Diseases; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Lymphocyte Count; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia is a common infection in patients with AIDS but an infrequent cause of pneumonia in cancer patients. Little is known about the impact of cancer type and hematopoietic stem cell transplantation on the presentation and outcome of P. jiroveci pneumonia in cancer patients. A retrospective cohort study of all patients with cancer and P. jiroveci pneumonia cared for at The M.D. Anderson Cancer Center during 1990-2003 was conducted. Eighty episodes of P. jiroveci pneumonia in 79 patients were identified. In most (67%) episodes, patients had a hematologic malignancy. In 23 (29%) episodes, patients had undergone hematopoietic stem cell transplantation. Twenty-seven percent of patients with histopathologically confirmed P. jiroveci pneumonia had nodular infiltrates on the radiographic study. Pleural effusion and pneumothorax were more common in patients with hematopoietic stem cell transplantation than in those with solid tumors. Clinical suspicion of P. jiroveci pneumonia was less common in patients with nodular infiltrates than in those without such a radiographic finding (7 vs. 39%; p=0.002). Twenty-six of 76 (34%) patients with data available died of P. jiroveci pneumonia. Predictors of death by univariate analysis included older age, tachypnea, high APACHE II score, use of mechanical ventilation or vasopressors, lower arterial pH level, absence of interstitial component, pneumothorax, and comorbid conditions (all p<0.05). Multivariate analysis identified the use of mechanical ventilation as an independent predictor of death. Death attributable to P. jiroveci pneumonia appeared to be higher in patients with hematopoietic stem cell transplantation. The clinical presentation of P. jiroveci pneumonia in cancer patients may be affected by the category of cancer and the history of hematopoietic stem cell transplantation. P. jiroveci pneumonia remains a rare yet severe infection in cancer patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anti-Infective Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Effective treatment of Pneumocystis jiroveci pneumonia (PCP) requires therapeutic serum concentrations of 5-10 microg/ml trimethoprim (TMP); consequently intravenous trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended therapy. However, oral therapy is desirable as the intravenous route is costly, time-consuming, more difficult to administer and carries a risk of needlestick injury.. To investigate whether therapeutic TMP levels for treatment of PCP can be attained with oral therapy in HIV-infected children.. A prospective dose-escalation study was undertaken of serum TMP levels attained following oral doses of TMP of 5 mg/kg, 10 mg/kg or 20 mg/kg in stable HIV-infected children. Children who received a 20 mg/kg dose were randomised to get a second dose (5 or 10 mg/kg TMP) at 6 hours. TMP levels were measured at baseline, peak (3 hours), and trough (6 hours) using liquid chromatography. An additional TMP level was taken at 9 hours in those who received a second TMP dose.. Median (25th-75th percentile) peak serum TMP levels following a 5 mg/kg, 10 mg/kg or 20 mg/kg oral loading dose were 0.93 (0.5-1.5) microg/ml, 1.94 (1.4-2.2) microg/ml and 7.68 (6.1-7.8) microg/ml respectively. Peak TMP levels at 9 hours after a second TMP dose of 5 or 10 mg/kg were 6.98 (3.4-8.8) microg/ml and 9.25 (8.2-10.3) microg/ml respectively.. Therapeutic concentrations of TMP for treatment of P. jiroveci can be attained with an oral loading dose of 20 mg/kg and sustained with a second dose at 6 hours of either 5 mg or 10 mg/kg in stable HIV-infected children.

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child, Preschool; Female; Humans; Infant; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Cardiac transplant recipients are often given prophylactic treatments to prevent opportunistic infections such as Pneumocystis carinii. Toxoplasmosis prophylaxis is commonly prescribed for transplant recipients who have not been exposed to this disease but receive a heart from an exposed donor. We reviewed the collective 28-year experience at two urban transplant programs with 596 patients, and found no cases of toxoplasmosis, but all patients received trimethoprim-sulfamethoxazole to prevent Pneumocystis pneumonia. We conclude that specific anti-toxoplasmosis prophylaxis is unnecessary in heart transplant recipients.

Topics: Adult; Anti-Infective Agents; Antiprotozoal Agents; Female; Follow-Up Studies; Graft Rejection; Heart Transplantation; Humans; Incidence; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Pyrimethamine; Retrospective Studies; Sulfadiazine; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Fever; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Middle Aged; Neutropenia; Paclitaxel; Pneumonia, Pneumocystis; Polyethylene Glycols; Prednisone; Recombinant Proteins; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Antibiotic Prophylaxis; Cystic Fibrosis; Humans; Lung Transplantation; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Presented here are two cases of multidrug-resistant Nocardia farcinica infection that occurred in immunocompromised patients. One of the patients developed the infection despite being on trimethoprim/sulfamethoxazole prophylaxis for Pneumocystis jiroveci. These cases demonstrate the propensity of Nocardia spp. to cause disseminated disease and to develop resistance to multiple antimicrobial agents used in the initial treatment of serious Nocardia infection. These factors lead to the conclusion that empiric monotherapy with trimethoprim/sulfamethoxazole may not be sufficient. Treatment with a combination regimen of imipenem and amikacin may be a more promising initial therapy.

Topics: Aged; Aged, 80 and over; Antibiotic Prophylaxis; Antifungal Agents; Drug Resistance, Multiple, Fungal; Female; Humans; Immunocompromised Host; Male; Nocardia; Nocardia Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Chorionic Gonadotropin, beta Subunit, Human; Female; Humans; Hydatidiform Mole, Invasive; Immunosuppressive Agents; Methotrexate; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Pregnancy; Respiratory Insufficiency; Retreatment; Trimethoprim, Sulfamethoxazole Drug Combination; Uterine Neoplasms; Vacuum Extraction, Obstetrical

Topics: Adult; Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Developing Countries; Humans; Patient Selection; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To examine the influence of cotrimoxazole (CTM) prophylaxis on incidence of lower respiratory tract infections (LRTIs) and diarrhoea.. A prospective observational cohort study. Morbidity and feeding data on infants born to HIV-infected mothers were collected routinely at clinic visits at 1 week, 6 weeks and 3 months, and 3-monthly thereafter, with blood drawn for determining HIV status.. Two hospitals in Durban, South Africa. In one hospital (King Edward VIII Hospital), infants born to HIV infected mothers received CTM prophylaxis and in the other (McCord Hospital) infants did not receive CTM prophylaxis.. Infants born to HIV-infected mothers. Outcome measures. Incidence of LRTI and diarrhoea.. In multivariate analysis controlling for breast-feeding status, number of clinic visits and HIV infection status, HIV infected infants with access to CTM prophylaxis had a significantly lower incidence of LRTI (82%) than those without access to prophylaxis. However in HIV-uninfected infants, this was not the case. CTM prophylaxis was associated with a non-significant increased risk for diarrhea in both infected (odds ratio (OR) 1.58, p = 0.45) and uninfected infants (OR 1.52, p = 0.10).. This observational study confirms current thinking that CTM prophylaxis is protective against LRTIs in HIV-infected children. However, because of a possible association between CTM prophylaxis and an increased risk of diarrhoea, HIV status of infants should be determined as early as possible in order to prevent unnecessary exposure of uninfected infants to CTM prophylaxis, while further studies to quantify both beneficial and adverse effects of CTM prophylaxis are undertaken.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Breast Feeding; Diarrhea, Infantile; Female; HIV Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Risk Factors; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination; Vitamin A

Topics: Agammaglobulinemia; Bone Marrow Transplantation; Bronchoalveolar Lavage Fluid; Drug Therapy, Combination; Dyspnea; Emergency Service, Hospital; Follow-Up Studies; Humans; Immunoglobulin M; Immunoglobulins, Intravenous; Infant; Male; Pneumonia, Pneumocystis; Pulmonary Eosinophilia; Risk Assessment; Syndrome; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Waiting Lists

Pneumocystis jiroveci pneumonia (PCP) has become a rare opportunistic infection due to the efficacy of prophylactic regimens. We conducted a 6-year retrospective study at our institution. A total of 13 cases of PCP were diagnosed among 519 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) (2.5%). In three patients, PCP occurred within the first 5 months following HSCT. These severely immunocompromised patients were receiving prophylaxis and had concomitant aspergillosis that caused rapid death in two of them. In 10 other patients, PCP occurred a median of 14.5 months after HSCT. In all these patients, PCP prophylaxis had been discontinued, mainly because of the suspected bone-marrow toxicity of the prophylactic regimen. Median CD4+ T cell count was 131/microl at diagnosis. Seven of these 10 patients were receiving immunosuppressive therapy for chronic graft versus host disease and three had a relapse of their hematological malignancy. One patient died from PCP despite high doses of cotrimoxazole. We conclude that PCP is still occurring after allogeneic HSCT, mainly as a late complication in patients in whom PCP prophylaxis had been prematurely discontinued. Long-term PCP prophylaxis should be maintained in patients receiving immunosuppressive drugs, and in those with low CD4+ T cell counts or a relapse of their hematological malignancy.

Topics: CD4 Lymphocyte Count; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Incidence; Opportunistic Infections; Pneumonia, Pneumocystis; Premedication; Retrospective Studies; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the clinical characteristics, therapeutical approaches and outcome of Pneumocystis pneumonia (PCP) in patients with AIDS.. The clinical data of 22 PCP patients with AIDS who were treated in Peking Union Medical College Hospital from January 1992 to October 2004 were analyzed, including the routes of HIV infection, clinical profiles, immunological status, chest radiological characteristics, therapeutic managements and outcome.. (1) Of the 22 PCP patients, 16 were male and 6 female. The average age was (35.0 +/- 9.4) years old. The majority of patients got HIV infection through blood transfusion (54.5%) and sexual transmission (27.3%). (2) The common clinical presentations were fever (21/22), progressive exertional dyspnea (20/22), cough (16/22), sputum (12/22) and weight loss (18/22). 68.2% (15/22) of the patients had normal or mild coarse breath sounds on auscultation. 14 patients had an PaO(2) less than 60 mm Hg (1 mm Hg = 0.133 kPa). (3) All the 22 PCP cases were in their late stage of AIDS. For the 20 patients who had an immunological test, the peripheral CD(4)(+) T lymphocyte count was ranging from 3 x 10(6)/L to 148 x 10(6)/L and 90% of the cases had a CD(4)(+) T cell count less than 100 x 10(6)/L, 95% of the cases had a CD(4)(+)/CD(8)(+) ratio less than 0.20; (4) The most common abnormal chest radiological findings were bilateral diffuse interstitial infiltrations (19/22) and patchy shadows (14/22); (5) All patients were given trimethoprim-sulfamethoxazole (SMZco) and 86.4% of the patients were treated with corticosteroids concomitantly. Of the 22 PCP patients, 13 recovered, 5 gave up after knowing their definite diagnosis, 4 died. Comparing with the recovery patients, the 4 patients who died of PCP had much lesser CD(4)(+) T cell count (P = 0.07).. Most PCP occurred in patients who were in their late stage of AIDS and with a CD(4)(+) T cell count below 100 x 10(6)/L. For these reasons, we suggest that whenever encountering a young patient presenting with fever, dyspnea, hypoxia, loss of weight, the possibility of PCP complicating AIDS should be considered, especially when chest radiological study revealed interstitial infiltration or patchy shadows. If HIV was confirmed to be positive, the combined therapy of SMZco and corticosteroids should be started immediately.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Radiography, Thoracic; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antibiotic Prophylaxis; Female; Follow-Up Studies; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Probability; Registries; Retrospective Studies; Risk Assessment; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

A 1.5-year-old girl developed high frequency tremors and chorea after receiving a dose of 120 mg/kg/d trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of Pneumocystis pneumonia. The child was human immunodeficiency virus-negative but immunocompromised because of prolonged immunosuppressive therapy. These symptoms disappeared 3 days after TMP-SMX was discontinued. Pediatricians should be aware of tremors and chorea among the potential adverse effects of high doses of TMP-SMX.

Topics: Anti-Infective Agents; Chorea; Female; Humans; Infant; Pneumonia, Pneumocystis; Tremor; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Anti-Retroviral Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Dapsone; Female; HIV Infections; Humans; India; Male; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Withholding Treatment

This study shows the long term safety of discontinuing secondary prophylaxis for Pneumocystis pneumonia in 5 human immunodeficiency virus-infected children who had recovered from a confirmed episode of Pneumocystis pneumonia, had <15% of CD4 cells at the time of starting highly active antiretroviral therapy and whose CD4 cell counts increased to >15% for >or=3 months during highly active antiretroviral therapy.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Chemoprevention; Drug Administration Schedule; HIV Infections; HIV-1; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

We present a 46-year-old African-American man with AIDS who was admitted on two different occasions within three weeks for signs and symptoms of meningitis after using trimethoprim/sulfamethoxazole (TMP/SMX). TMP/SMX is primarily used for the treatment of pneumocystis carinii pneumonia prophylaxis in AIDS patients. Drug-induced aseptic meningitis (DIAM) is commonly seen with nonsteroidal anti-inflammatory drugs (NSAIDS), antibiotics (with TMP/SMX being the most frequently implicated), intravenous immunoglobulins and OKT3 antibodies. However, the implication of TMP/SMX inducing aseptic meningitis has been underreported to FDA/MEDWATCH program. This might be due to the fact that it has also been used to treat bacterial meningitis from organisms like Listeria monocytogenes, which is a common pathogen in the elderly and in infants. We reviewed the literature in an attempt to characterize the pattern and predictors of TMP/SMX-induced aseptic meningitis.

Topics: Acquired Immunodeficiency Syndrome; Adverse Drug Reaction Reporting Systems; Anti-Infective Agents; Humans; Male; Meningitis, Aseptic; Middle Aged; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

We evaluated the clinical features of pneumocystis jiroveci pneumonia (PCP) as a complication of glucocorticoid therapy for interstitial pneumonia We analyzed 74 interstitial pneumonia patients receiving glucocorticoid therapy, of whom 7 patients developed PCP. At the time of PCP diagnosis, the average duration of the glucocorticoid therapy was 71 days and the average daily dose of predonisolone was 37 mg. Circulating CD4+ lymphocyte counts were 370/microl on the average and more than 200/microl in three cases. PCP cases showed less circulating lymphocyte counts four weeks after the initiation of the therapy. Any cases receiving sulfamethoxazole-trimethoprim (TMP-SMX) did not develop PCP. In conclusion, interstitial pneumonia patients, who are treated with glucocorticoid, are benefit from TMP-SMX as PCP prophylaxis, but CD4 + lymphocyte counts greater than 200/microl is no reason to denying PCP.

Topics: Aged; Anti-Infective Agents; Drug Administration Schedule; Female; Glucocorticoids; Humans; Lung Diseases, Interstitial; Male; Middle Aged; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisolone; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

A 6-month-old male Quarter Horse was evaluated for chronic respiratory tract disease. Diagnostic investigations revealed pulmonary inflammation; Pneumocystis carinii was detected within macrophages. Lymphocyte subpopulation phenotyping and immunoglobulin concentration analysis were performed and results suggested immune suppression. Trimethoprim-sulfamethoxazole administration was initiated; the colt was discharged but was reexamined 8 days later because of profuse diarrhea and endotoxemia. Bacterial culture of feces recovered Salmonella spp resistant to trimethoprim-sulfamethoxazole, and a diagnosis of antimicrobial-associated colitis was made. Bilateral fibrinous hypopyon developed and was treated with topical medication and intracameral injections of human recombinant tissue plasminogen activator. Dapsone (3 mg/kg [1.4 mg/lb], PO, q 24 h; dose extrapolated from human data) was administered for treatment of P carinii pneumonia (56-day treatment period). The colt recovered from the pneumonia and diarrhea. Dapsone may be a useful adjunct to traditional treatment for P carinii pneumonia in horses or as a sole medication for horses that cannot tolerate other treatments.

Topics: Animals; Anti-Infective Agents; Dapsone; Diarrhea; Horse Diseases; Horses; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Primary infection with Pneumocystis carinii usually occurs early in life, and young infants receiving prolonged treatment with high-dose corticosteroids may be at risk for the development of symptomatic disease. Prophylaxis with trimethoprim-sulfamethoxazole is safe and effective and should be considered for such infants, particularly those with underlying airway abnormalities. We describe a 3-month-old immunocompetent infant who developed severe P carinii pneumonia after 6 weeks of high-dose corticosteroid therapy for cervicofacial and airway hemangiomas.

Topics: Anti-Infective Agents; Female; Glucocorticoids; Head and Neck Neoplasms; Hemangioma; Humans; Infant; Pneumonia, Pneumocystis; Prednisolone; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia in patients with chronic lymphocytic leukaemia (CLL) who have not been treated with fludarabin are rare, although clinically relevant CD4 T-cell depletion can occur in longstanding CLL without prior treatment with purine analogues. A 52 year old woman is reported who was on long term treatment with chlorambucil and taking a short course of prednisone for familial CLL before she developed progressive dyspnoea, and P carinii pneumonia was diagnosed in bronchoalveolar lavage fluid. Despite treatment with high dose co-trimoxazole the patient died.

Topics: Anti-Infective Agents; Antineoplastic Combined Chemotherapy Protocols; Chlorambucil; Dyspnea; Fatal Outcome; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Middle Aged; Opportunistic Infections; Pedigree; Pneumonia, Pneumocystis; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole is the preferred agent for prophylaxis against Pneumocystis jiroveci pneumonia. Alternative agents are used in treating patients who do not tolerate this medication. We report 2 cases of prophylaxis failure in patients receiving low-dose atovaquone. We discuss the use of atovaquone as an alternative agent for prophylaxis in transplant recipients.

Topics: Aged; Antifungal Agents; Atovaquone; Chemoprevention; Humans; Liver Transplantation; Male; Middle Aged; Naphthoquinones; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

This study of Pneumocystis carinii dihydropteroate synthase (DHPS) mutations in patients with AIDS who have P. carinii pneumonia compares the change in the prevalence of such mutations in the United States, where sulfa-drug prophylaxis is widespread, to that in China, where it is infrequent. The DHPS gene from 145 US patients presenting during 1983-2001 and from 15 Chinese patients presenting during 1998-2001 was amplified by polymerase chain reaction and was sequenced. In the United States, 40% of patients had DHPS mutations; 38% received sulfa-drug prophylaxis. Mutation prevalence increased to 70% during 2000-2001, from 25% during 1994-1995 (P<.01). In China, 7% of patients had DHPS mutations; none received sulfa-drug prophylaxis. The prevalence of P. carinii DHPS mutations has markedly increased in the United States but remains low in China.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chemoprevention; China; Dapsone; Dihydropteroate Synthase; Female; Humans; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; United States

We studied all human immunodeficiency virus (HIV)-infected patients with invasive pneumococcal disease who received their diagnosis during 1996-2002 to investigate the incidence of this disease in the highly active antiretroviral therapy era and to study the influence of CD4 lymphocyte count on the clinical presentation and outcome of disease. The overall incidence of invasive pneumococcal disease was 11.3 cases per 100,000 person-years in adult patients without known HIV infection and 677 cases per 100,000 person-years in HIV-infected patients. This incidence remained stable over the study period. Clinical presentation, severity of illness, and number of recurrent episodes were similar in patients with CD4+ cell counts of >200 or < or =200 cells/ microL. Patients receiving trimethoprim-sulfamethoxazole (TMP-SMZ) were more likely to present with TMP-SMZ-resistant pneumococci than were those who were not receiving this agent (76.7% vs. 43.6%; P=.007). The mortality rate was high (21%).

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Animals; Antiretroviral Therapy, Highly Active; Comorbidity; Drug Resistance, Multiple, Bacterial; Female; HIV; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Pneumococcal Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Streptococcus pneumoniae; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim Resistance; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a 58-year-old patient with relapsing high-grade non-Hodgkin's lymphoma who exhibited exacerbation of posthypoxic action myoclonus during high-dose intravenous trimethoprim-sulfamethoxazole (TMP-SMX) treatment for highly suspicious Pneumocystis jiroveci pneumonia (PCP). Three months previously the patient had experienced a hypoxic insult caused by respiratory arrest due to an anaphylactic reaction to antibiotic therapy. He had developed posthypoxic action myoclonus (Lance-Adams syndrome), which was well controlled by oral treatment with piracetam. However, after TMP-SMX therapy (115 mg/kg daily) was started for suspicion of newly developed PCP, posthypoxic action myoclonus worsened dramatically resulting in complete disability. Anti-myoclonic therapy with increased doses of piracetam and valproic acid did not significantly improve his clinical condition. Only when TMPSMX doses were reduced (38 mg/kg daily) on day 12 did action myoclonus cease within 2 to 3 days. We suggest that TMP-SMX can exacerbate posthypoxic action myoclonus.

Topics: Anti-Infective Agents; Humans; Hypoxia; Immunocompromised Host; Male; Middle Aged; Myoclonus; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A 64-year-old man was admitted to our hospital complaining of dyspnea and fever. He had been treated with low-dose methotrexate for rheumatoid arthritis. Chest radiography showed diffuse ground-glass attenuation in both lung fields, and hypoxia was detected. Pneumosystis carinii pneumonia was demonstrated on transbronchial lung biopsy, and the serum beta-D glucan level was high. We started treatment with trimethoprim-sulphamethoxazole, but respiratory failure worsened, and drug-induced pancytopenia occurred. Although trimethoprim-sulphamethoxazole was stopped, pancytopenia persisted and the patient required ventilatory support. After we changed the medication from trimethoprim-sulphamethoxazole to pentamidine, respiratory failure improved. It was thought that pneumocystis carinii pneumonia was associated with low-dose methotrexate and that trimethoprim-sulphamethoxazole interacted with methotrexate to induce severe pancytopenia.

Topics: Anti-Infective Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Male; Methotrexate; Middle Aged; Pancytopenia; Pneumonia, Pneumocystis; Pulse Therapy, Drug; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Anti-Infective Agents; Drug Resistance, Microbial; HIV Infections; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Factors; South Africa; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chemoprevention; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Pneumonia, Pneumocystis; Risk Assessment; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

PRESENTING FEATURES: A 53-year-old man who had human immunodeficiency virus (HIV) presented to the Johns Hopkins Hospital with a 3-month history of increasing dysphagia, cough, dyspnea, chest pain, and an episode of syncope. His past medical history was notable for oral and presumptive esophageal candidiasis that was treated with fluconazole 6 months prior to presentation. Three months prior to presentation, he discontinued his medications, and his symptoms of dysphagia recurred. During that time he developed intermittent fevers and chills, progressively worsening dyspnea on exertion, and a cough productive of white sputum. He also reported a 40-lb weight loss over the past 3 months. On the day prior to presentation, he had chest pain and shortness of breath followed by weakness, dizziness, and a brief syncopal episode. He denied orthopnea, paroxysmal nocturnal dyspnea, lower extremity edema, jaundice, hemoptysis, hematemesis, melena, hematochezia, or diarrhea. There was no history of alcohol use, and he stopped smoking tobacco approximately 1 month previously. He smoked cocaine but denied injection drug use. The patient had never been on antiretroviral therapy and had never had his CD4 count or viral load measured. On physical examination, the patient was a thin, cachectic man who appeared older than his stated age. His vital signs were notable for blood pressure of 102/69 mm Hg, resting tachycardia of 102 beats per minute, resting oxygen saturation of 92% on room air, normal resting respiratory rate, and a temperature of 38.1 degrees C. His oropharynx was clear, with no signs of thrush or mucosal ulcers. His pulmonary examination was notable for diminished breath sounds in the lower lung fields bilaterally. Cardiac, abdominal, and neurologic examinations were normal. His skin was intact, with no visible petechiae, rashes, nodules, or ulcers. Laboratory studies showed a total white blood cell count of 3.2 x 10(3)/microL, with a total lymphocyte count of 330/microL, hematocrit of 30.2%, a serum sodium level of 129 mEq/L, and a serum lactate dehydrogenase level of 219 IU/L. The patient had an absolute CD4 count of 8 cells/mm3 and a HIV viral load of 86,457 copies/mL. His arterial blood gas on room air had a pH of 7.51, a PCO2 of 33 mm Hg, and a PO2 of 55 mm Hg. Electrocardiogram and serial serum cardiac enzymes were normal. A chest radiograph showed bilateral upper lobe patchy infiltrates with left upper lobe consolidation. Computed tomographic (CT) scan o

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Chest Pain; Cough; Deglutition Disorders; Diagnosis, Differential; Drug Therapy, Combination; Dyspnea; Humans; Lung Diseases, Fungal; Male; Middle Aged; Pneumonia, Pneumocystis; Prednisone; Sporotrichosis; Syncope; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP) is a major cause of mortality in human immunodeficiency virus (HIV)-infected infants in Africa, but the prevalence of mutations in the gene encoding dihydropteroate synthase (DHPS) in isolates from Africa has not been reported.. This study investigated the prevalence of DHPS mutations in P. jiroveci isolates from South African HIV-infected children with PCP by amplifying DNA using 2 different polymerase chain reactions.. P. jiroveci DNA from 30 respiratory specimens was amplified; 26 specimens (86.7%) contained wild-type DHPS alleles. Of the 4 samples (13.3%) with DHPS mutations, 2 contained a homogenous population with single DHPS mutations, 1 contained a homogenous population with 2 DHPS mutations, and the fourth contained a heterogenous population of organisms with both wild-type and single-mutant DHPS genotypes. Only 1 child was receiving trimethoprim-sulphamethoxazole (TMP-SMZ) prophylaxis; this patient was infected with wild-type P. jiroveci. The mortality rate (overall, 20 [66.7%] of 30 children) was not significantly different between children infected with wild-type P. jiroveci (17 [65.4%] of 26) and those infected with mutant strains (3 [75%] of 4; P=.8).. DHPS mutations are uncommon in P. jiroveci isolates from South Africa. However, increasing use of TMP-SMZ prophylaxis may result in widespread development of mutations.

Topics: AIDS-Related Opportunistic Infections; Dihydropteroate Synthase; HIV Infections; Humans; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Prospective Studies; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Follow-Up Studies; Humans; Immunocompromised Host; Immunosuppressive Agents; Methotrexate; Pneumonia, Pneumocystis; Prednisolone; Radiography, Thoracic; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the early diagnosis, treatment and prevention of pneumocystosis complicated after renal transplantation.. Data from 12 cases of kidney transplant recipients who developed pneumocystosis were analyzed by clinical symptoms and signs, results of laboratory examination, imaging, bronchoscopy and biopsy. Combined TMP/SMZ was used for the prevention and treatment.. Pneumocystis carinii (Pc) detection rate was 16.7% from alveolar douche, 66.7% with bronchoscopy and biopsy. Two cases was diagnosed by PCR method with sputum. Plain chest film showed 58.3% of lung cirrhosis. CT showed 50% frosted glass-like change in lungs and 25% with lung consolidation. Eleven cases were cured but one died.. Pc detection by bronchoscopy and biopsy, and PCR are most helpful in the diagnosis of pneumocystosis complicated with renal transplantation, in addition to plain chest film and CT scaning. Combined TMP/SMZ is effective in the prevention and treatment of pneumocystosis.

Topics: Adolescent; Adult; Anti-Infective Agents; Female; Glomerulonephritis; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Pneumonia, Pneumocystis; Postoperative Complications; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: 2-Aminopurine; Alemtuzumab; Antibiotic Prophylaxis; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antigens, CD; Antigens, Neoplasm; Antineoplastic Agents; Bone Marrow Transplantation; CD52 Antigen; Clinical Trials as Topic; Cytomegalovirus Infections; Disease Susceptibility; Famciclovir; Ganciclovir; Glycoproteins; Graft vs Host Disease; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Incidence; Infections; Lymphoproliferative Disorders; Opportunistic Infections; Pneumonia, Pneumocystis; Rituximab; Transplantation Conditioning; Trimethoprim, Sulfamethoxazole Drug Combination; Viremia; Virus Activation

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; Arthritis, Infectious; Drug Therapy, Combination; Hepatitis C, Chronic; HIV Infections; Humans; Knee Joint; Male; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Pneumocystis carinii; Pneumonia, Pneumocystis; Substance Abuse, Intravenous; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Multidrug-Resistant; Tuberculosis, Osteoarticular

A multivariate analysis using a logistic regression model evaluated odds ratio (OR) and 95% confidence limits (95% CL) of pediatrician-diagnosed wheezing respiratory illness in 75 infants with perinatal human immunodeficiency virus-type 1 (HIV-1) infection, 205 uninfected infants of HIV-1 infected mothers, and 1780 infants of HIV-1 uninfected mothers. Infants were prospectively followed-up for the first 2 years of life. Covariates were risk factors for wheezing respiratory illness (preterm delivery, low birth weight, maternal smoking, formula feeding, and neonatal respiratory disorders). Maternal use of illicit drugs in pregnancy, antiretroviral treatment in pregnancy, maternal HIV-1-related clinical condition at the time of delivery were also included in the models when infants of HIV-1 infected mothers were taken into account. Although the frequency of risk factors for wheezing respiratory illness was higher in infants of HIV-1 infected than in those of uninfected mothers, HIV-1 infection emerged as a protective factor [OR: 0.001 (95% CL: 0.0001-0.01); p < 0.001]. The frequency of risk factors was similarly high among infants of infected mothers, but OR was lower in HIV-1 infected than in uninfected infants of infected mothers (0.005; 95% CL: 0.0004-0.06; p < 0.001). Finally, OR was higher in uninfected infants of HIV-1 infected mothers (who evidenced a higher frequency of risk factors) than in infants of HIV-1 uninfected mothers (9.97; 95% CL: 4.87-20.40; p < 0.001). Understanding the reason why HIV-1 protects against wheezing respiratory illness could shed light on the immunologic and inflammatory mechanisms of airway obstruction.

Topics: Adult; Airway Obstruction; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Chemoprevention; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Infant Welfare; Infant, Low Birth Weight; Infant, Newborn; Infant, Newborn, Diseases; Male; Maternal Welfare; Mother-Child Relations; Pneumonia, Pneumocystis; Pregnancy; Pregnancy Complications, Infectious; Prospective Studies; Protease Inhibitors; Respiratory Sounds; Reverse Transcriptase Inhibitors; Risk Factors; Severity of Illness Index; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Changes in the number of alveolar macrophages were correlated with organism burden during Pneumocystis carinii infection. The lungs of healthy, dexamethasone-treated, and dexamethasone-treated and P. carinii-infected rats were lavaged with phosphate-buffered saline. Counting of alveolar macrophages in the lavage fluids revealed that P. carinii infection caused a 58% decrease in the number of alveolar macrophages and that higher P. carinii organism burdens caused a more rapid decrease in alveolar macrophage number. As a control, healthy rats were challenged with the same number of organisms as that normally used to generate P. carinii infections in dexamethasone-treated rats. Thirteen days after challenge, these rats had a profound (54%) increase in alveolar macrophage number in response to the challenge, while the number of alveolar macrophages in immunosuppressed and P. carinii-infected rats had decreased significantly by this time point. These experiments created the first animal model to mimic human pneumocystis pneumonia in alveolar macrophage number alterations. Reduction of P. carinii organism numbers by treatment of rats with trimethoprim and sulfamethoxazole brought a slow rebound in alveolar macrophage number, while recovery from P. carinii infection by cessation of immunosuppression brought a rapid rebound in alveolar macrophage number. These results suggest that both the immune state of the host and P. carinii burden affect alveolar macrophage number.

Topics: Animals; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Cell Count; Dexamethasone; Female; Glucocorticoids; Lung; Macrophages, Alveolar; Pneumocystis; Pneumonia, Pneumocystis; Rats; Rats, Sprague-Dawley; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Africa; Chemoprevention; Child; Child, Preschool; Humans; Patient Compliance; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

One hundred ninety-four bronchoalveolar specimens were evaluated by microscopic examination and by amplification of a sequence of a Pneumocystis carinii dihidropteroate synthase gene for identification of mutations linked to sulfa resistance. PCR sensitivity and specificity were 100 and 86.7%, respectively, compared to results of microscopic examination. However, 7 out of 19 microscopy-negative, PCR-positive samples were collected from subjects with a clinically high probability of P. carinii pneumonia, suggesting that PCR may be more sensitive than microscopic examination, although the absolute performance of PCR cannot be determined. Mutations were identified in 28 out of 70 (40%) PCR-positive specimens and were significantly more common in patients exposed to sulfa drugs (21 out of 29 [72.4%]) than in those not exposed to sulfa drugs (4 out of 35 [11.4%]).

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Dapsone; Dihydropteroate Synthase; Drug Resistance, Fungal; Humans; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Sensitivity and Specificity; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Angioedema; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Tolerance; Female; HIV Infections; Humans; Infant; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Diagnosis, Differential; Female; HIV Seronegativity; Humans; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the outcome of Legionnaires disease (LD) in patients with and without HIV infection.. Retrospective review of clinical charts.. Six hundred-bed university hospital.. We studied the clinical findings of 64 patients without HIV and 15 patients with HIV. Patients with a serologic diagnosis only were not included. Patients with previous immunosuppressive therapy or transplant recipients were excluded from the former group. In the HIV group, the mean CD4 cell count was 347.5/ microL, plasma viral load was undetectable in 50% of the patients, and only one patient (7%) was receiving cotrimoxazole as prophylaxis against Pneumocystis carinii at the time of pneumonia. No differences were observed in the two groups with respect to community or nosocomial acquisition, delay in the initiation of appropriate treatment, the use of macrolides or fluoroquinolones, and Fine score in cases of community-acquired LD.. Univariate analysis showed that time to apyrexia was longer, and respiratory symptoms, bilateral infiltrates in chest radiograph, hyponatremia, increase in aspartate aminotransferase and creatine phosphokinase (CK), and respiratory failure were more frequent in the HIV group. Mortality was greater in patients with HIV, achieving a statistically significant value of 20%; however, multivariate analysis only confirmed these differences with respect to the increase in CK.. LD has a more severe clinical presentation and worse evolution in patients with HIV.

Topics: Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Legionnaires' Disease; Male; Medical Records; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

Pneumocystis carinii infection is rare in infants, and raises strong concerns of immune deficiency. This report describes the unusual case of a male infant with concurrent chest infections caused by P carinii and cytomegalovirus. Investigation was complicated by the strong suspicion of non-accidental injury, including subdural haematomas. The case illustrates how to investigate for possible immunodeficiency. Low immune function tests at presentation slowly improved and have remained normal on longterm follow up. Possible explanations for the transient severe clinical immunodeficiency in this case are discussed.

Topics: Anti-Bacterial Agents; Antiviral Agents; Child Abuse; Cytomegalovirus Infections; Ganciclovir; Hematoma, Subdural; Humans; Immunocompromised Host; Infant; Infectious Disease Transmission, Vertical; Male; Pneumonia, Pneumocystis; Rib Fractures; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) can occur in immunocompromised patients without HIV infection. Risk factors, clinical features, treatment outcomes, and factors related to mortality in these patients may be useful clinical data for physicians who care for these patients.. A retrospective study of PCP patients without HIV infection at Ramathibodi Hospital, from 1994 to 2001, was conducted. Only cases with microbiological and/or pathological proven were included.. There were 19 patients with 42.1 per cent males and a mean age of 44.6 years. All patients had underlying immunocompromised diseases. 94.7 per cent of the cases received immunosuppressive drugs. PCP occurred at a mean duration of 26.4 months after the diagnosis and treatment of underlying diseases. Common clinical presentations of PCP were progressive dyspnea, fever, and non-productive cough. All patients had abnormal chest radiography with a majority of bilateral interstitial infiltration (63.2%). Diagnosis of PCP was confirmed with microbiological examination from bronchoalveolar larvage (84.2%) and pathological diagnosis from transbronchial biopsy (15.8%). Almost all of the cases (94.7%) were treated with co-trimoxazole. Ten patients (52.6%) had concomitant bacterial pneumonia or fungal pneumonitis. Overall mortality rate was 36.8 per cent. Mortality was significantly higher in patients who needed mechanical ventilation (p = 0.006). There was a trend toward a higher mortality rate in patients with concomitant pulmonary diseases (p = 0.09).. PCP may complicate a variety of immunocompromised states especially autoimmune diseases and hematologic malignancy. Patients who receive corticosteroids and/or cytotoxic drugs should receive primary PCP prophylaxis. The mortality rate is high especially in severe cases that need mechanical ventilation. Intensive care and close monitoring are needed for these patients.

Topics: Adult; Aged; Anti-Infective Agents; Comorbidity; Female; Humans; Immunocompromised Host; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Atovaquone; Clinical Protocols; Dapsone; Drug Therapy, Combination; HIV Infections; Hospital Administration; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Retreatment; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Chemoprevention; Child; Drug Combinations; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Diagnosis, Differential; Fatal Outcome; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Homosexuality, Male; Humans; Male; Pneumonia, Pneumocystis; Secondary Prevention; Social Environment; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acidosis; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Hydrogen-Ion Concentration; Male; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Although several studies have reported that it is safe to discontinue secondary Pneumocystis carinii pneumonia (PCP) prophylaxis in patients infected with HIV who experience a sustained immune response as a result of antiretroviral therapy, we describe a patient who developed recurrent PCP <3 months after discontinuing trimethoprim-sulfamethoxazole prophylaxis. He developed disease despite a sustained CD4 T-cell count above 200 cells/microL for more than 3 years while on antiretroviral therapy, as well as an apparent immune reconstitution against disseminated Mycobacterium avium complex (MAC) and Histoplasma capsulatum, for which he also discontinued therapy but without adverse effects. Thus, although increasing evidence continues to indicate that HIV-infected patients receiving combinations of antiretroviral therapies may regain specific immunity against opportunistic infections, our patient's experience suggests that this immune recovery may be selective and incomplete.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Humans; Male; Pneumonia, Pneumocystis; Secondary Prevention; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

This report describes a child who develops Pneumocystis carinii pneumonia 7 months after high-dose chemotherapy for stage IV neuroblastoma. In addition to chemotherapy the child had also been treated with abdominal radiotherapy and 13-cis-retinoic acid. Standard practice has been to treat patients with prophylactic co-trimoxazole for 3 months after high-dose therapy, but this report highlights the intensity and complexity of current treatment for stage IV neuroblastoma and the need to be aware of prolonged lymphopenia after such treatment.

Topics: Abdominal Neoplasms; Adrenal Cortex Hormones; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child, Preschool; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Etoposide; Fatal Outcome; Female; Humans; Immunocompromised Host; Isotretinoin; Neoplasm Staging; Neuroblastoma; Opportunistic Infections; Pneumonia, Pneumocystis; Radiotherapy, Adjuvant; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

Topics: Amino Acid Substitution; Antifungal Agents; Humans; Mutation, Missense; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymorphism, Genetic; Tetrahydrofolate Dehydrogenase; Trimethoprim, Sulfamethoxazole Drug Combination

The dihydropteroate synthase (DHPS) gene from Pneumocystis carinii isolated from non-human primates was amplified using a polymerase chain reaction (PCR) and sequenced to analyse point mutations associated with sulfa resistance. P. carinii DHPS gene amplification was obtained from eight lung samples from five New World primate species and one Old World primate species. None of the animals had been exposed to sulfa drugs and only the wild-type P. carinii DHPS sequence at codons 55 and 57 was observed. These data support the hypothesis that high rates of DHPS mutants in P. carinii f. sp. hominis have arisen with increased use of sulfa drugs for P. carinii pneumonia prophylaxis.

Topics: Amino Acid Sequence; Animals; Animals, Zoo; Antifungal Agents; Cebidae; Cercopithecidae; Dihydropteroate Synthase; Drug Resistance, Fungal; France; Genes, Fungal; Lung; Molecular Sequence Data; Monkey Diseases; Pneumocystis; Pneumonia, Pneumocystis; Point Mutation; Sequence Alignment; Strepsirhini; Trimethoprim, Sulfamethoxazole Drug Combination

HIV-associated infections in sub-Saharan Africa differ markedly in their incidence from those in industrialized countries. Tuberculosis is the commonest cause of morbidity and mortality. Enteric pathogens such as microsporidiosis commonly cause disease as access to safe water is limited. Pneumocystis carinii pneumonia, which is the commonest opportunistic infection in industrialized countries, is uncommon in adults with HIV infection. This remains unexplained because P. carinii pneumonia is common in Black African HIV-infected children. Cytomegalovirus and Mycobacterium avium complex, which only occur in severely immune-suppressed individuals, are seldom found. One reason may be that survival after conversion to AIDS is relatively short in Africa. Patients often die before they develop severe immune suppression. Recently, prophylactic cotrimoxazole treatment was shown to be effective in symptomatic HIV-infected adults in Africa. Tuberculosis preventive therapy is also effective in Africa, at least in the medium term. It is hoped that these two affordable interventions will become available to large numbers of patients identified in voluntary counselling and testing centres.

Topics: Adult; Africa; Africa South of the Sahara; AIDS Serodiagnosis; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antitubercular Agents; Black People; Child; Cytomegalovirus Infections; Developed Countries; Developing Countries; HIV Seropositivity; Humans; Incidence; Microsporidiosis; Mycobacterium avium-intracellulare Infection; Pneumonia, Pneumocystis; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Pneumocystis carinii pneumonia (PCP) poses a serious risk to allogeneic bone marrow transplant (BMT) patients, who are often intolerant of trimethoprim-sulfamethoxazole (TMP-SMX), the traditional first-line prophylactic agents. There are limited published data supporting the use of aerosolized pentamidine (AP) prophylaxis in the BMT population. We assessed the effectiveness of AP in BMT recipients by reviewing the experience at our center. We divided our review into four time periods from January 1990 to March 2000, during which approximately 700 BMTs were performed. The first period includes patients receiving AP treatments from January 1990 to July 1997 (baseline), the second from August 1997 to July 1998 (pre-outbreak), the third from August 1998 to October 1999 (outbreak), and the fourth from November 1999 to March 2000 (post-outbreak). At our center, TMP-SMX is the first-line agent for PCP prophylaxis, which is routinely continued for at least one year, or for the duration of enhanced immunosuppression. During the baseline period, 505 BMTs were performed and 192 patients (38%) received AP for part of their time at risk. Six patients (3%) experienced toxicities requiring discontinuation of AP. Three cases of PCP were diagnosed over 1114 patient-months of treatment in the baseline period. During the last 42 months of the baseline period, 2/154 patients receiving AP and 2 of an estimated 293 patients receiving exclusively oral prophylaxis developed breakthrough PCP (p = 0.61). During the outbreak period, 9 of 180 patients receiving AP developed PCP compared to none in the group receiving exclusively oral prophylaxis. Either changes in our AP protocol during the pre-outbreak period or pentamidine resistance may have led to this failure of prophylaxis. There were no further cases during the 5-month post-outbreak period. Our observed overall breakthrough rate was 12 cases out of 439 patients (2.7%). Our study shows that AP is an effective and well-tolerated second-line agent in preventing PCP post BMT and we recommend its continued use in this regard. However, it should be administered using a well-studied protocol, and only when TMP-SMX is not tolerated.

Topics: Administration, Inhalation; Antiprotozoal Agents; Bone Marrow Transplantation; Female; Humans; Immunosuppressive Agents; Male; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To report our experience in diagnosis and treatment of AIDS complicated by Pneumocystis Carinii Pneumonia (PCP), and explore the relations between preventive medication and occurrence as well as recurrence of PCP.. The clinical characteristics of 20 patients with AIDS complicated by PCP (identified from a cohort of 109 patients with AIDS) treated in our hospital during July 2000 to May 2002 were analyzed.. All the 20 cases had fever, 90 % of whom also had cough or expectoration, and chest radiography revealed bilateral interstitial changes in 80 % of the cases.. It is possible to diagnose PCP by typical clinical findings and chest X-ray, and compound sulfamethoxazole may prove effective for preventing the occurrence of PCP.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The case of a patient with a newly diagnosed HIV infection and Pneumocystis carinii pneumonia is presented. Despite treatment with high-dose trimethoprim/sulfamethoxazole (TMP/SMX) and prednisone with initial improvement, the patient acutely deteriorated with severe acidosis and died on the 4th day of hospitalization. Cryptococcus neoformans grew the next day in broncheoalveolar lavage (BAL) and blood culture. As simultaneous presence of more than one opportunistic infection can occur in these patients, systematic workup for other common opportunistic infections must be performed.

Topics: Adult; AIDS-Related Opportunistic Infections; Cryptococcosis; Disease Progression; Drug Therapy, Combination; Fatal Outcome; Humans; Male; Pneumonia, Pneumocystis; Prednisone; Risk Assessment; Sepsis; Severity of Illness Index; Trimethoprim, Sulfamethoxazole Drug Combination

African human immunodeficiency virus type 1 (HIV-1)-infected children were evaluated to define the burden of Pneumocystis carinii pneumonia (PCP) and its interaction with bacterial and viral pathogens. P. carinii was identified in 101 (43.7%) of 231 episodes of pneumonia among 185 HIV-1-infected children (median age, 4.5 months; range, 1.7-27.3 months). Receipt of trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis was not associated with a significant reduction (36%; 95% confidence interval [CI], -15.4% to 64.5%) in isolation of P. carinii among children considered to have received adequate prophylaxis (37.7% of children) compared with children who had never received any prophylaxis (48.5% of children). However, deaths among children with PCP who had been taking TMP-SMX prophylaxis were markedly reduced (98.6%; 95% CI, 89.1%-99.8%) compared with children who were not taking prophylaxis. Concurrent P. carinii infection was observed in 6 of 18, 11 of 26, and 4 of 6 HIV-1-infected children who had bacteremia, a respiratory virus isolated, or Mycobacterium species isolated, respectively.

Topics: Africa; Anti-Infective Agents; Antibiotic Prophylaxis; Child, Preschool; Humans; Infant; Infant, Newborn; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Diseases

A case of severe dyspnea, hypercalcemia and renal failure secondary to sarcoidosis is reported. The clinical diagnosis of sarcoidosis in a 48-year-old man was confirmed by histology and cytology. Transiently decreased numbers of CD4+ T cells (282/microliter) indicated impaired immunity in the absence of HIV-infection during the acute phase of the disease. Surprisingly, numerous "trophozoites" of Pneumocystis carinii were detected by immunofluorescence staining and PCR in the bronchoalveolar fluid indicating infection or colonization of the lungs. Corticosteroid therapy was administered together with trimethoprim-sulfamethoxazole and rapidly reduced elevated serum calcium and creatinine concentrations. Since airborne person-to-person transmission of P. carinii to susceptible individuals might be possible, patients with sarcoidosis could be a previously unrecognized reservoir for P. carinii distribution in hospitals and in the community at large.

Topics: CD4 Lymphocyte Count; Drug Therapy, Combination; Humans; Hypercalcemia; Immune Tolerance; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Prednisone; Renal Insufficiency; Sarcoidosis, Pulmonary; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Humans; Immunologic Deficiency Syndromes; Infant; Male; Pneumocystis; Pneumonia, Pneumocystis; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; HIV Infections; Humans; Infant; Infectious Disease Transmission, Vertical; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci is a common cause of pneumonia in South African patients with AIDS. Sulphonamide resistance may become a problem in South Africa, as patients are treated with prophylactic co-trimoxazole when their CD4 counts fall below 200 cells/microliter. Failure of prophylaxis and treatment has been observed, possibly due to infection with sulphonamide-resistant strains. Sulphonamide resistance has been reported elsewhere, and is due to point mutations at codons 55 and 57 of the dihydropteroate synthase gene. Strain typing is useful for molecular epidemiological purposes.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Comorbidity; Drug Resistance, Bacterial; Humans; Pneumocystis; Pneumonia, Pneumocystis; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

This study examined gene polymorphisms in dihydropteroate synthase (DHPS), dihydrofolate reductase (DHFR) and cytochrome b of Pneumocystis carinii isolated from 34 patients with P. carinii pneumonia (PCP) in Japan. Four amino acid substitutions (Thr55Ala, Pro57Ser, His60Gln and Glu169Gly) in DHPS, 2 mutations (Ala67Val and Cys166Tyr) in DHFR and 1 mutation (Leu280Phe) in cytochrome b were found in 9 (26.5%), 2 (5.9%) and 1 (2.9%) patient, respectively. No linkage of mutations in DHPS to those in DHFR or cytochrome b was observed. The patients whose isolates showed mutations in DHPS, DHFR and cytochrome b were not exposed to sulfonamides, DHFR inhibitors and atovaquone before they developed PCP, except for 2 patients. Co-trimoxazole treatment failed more frequently in patients whose isolates had DHPS mutations than in those whose isolates showed wild-type DHPS (n=6 [85.7%] versus n=3 [12.5%]; P=0.001). Our results suggest that DHPS mutations may contribute to failure of co-trimoxazole treatment for PCP.

Topics: Amino Acid Substitution; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Cytochromes b; Dihydropteroate Synthase; Humans; Japan; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Reverse Transcriptase Polymerase Chain Reaction; Tetrahydrofolate Dehydrogenase; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii is a common cause of pneumonia in patients with AIDS, however, the incidence has dropped with the availability of effective prophylactic regimens. First-line treatment for both acute Pneumocystis pneumonia and chronic prophylaxis is trimethoprim/sulfamethoxazole (TMP/SMX). This combination can cause hypersensitivity reactions as well as myelosuppression. The simultaneous administration of leucovorin during acute treatment has been shown to reduce the incidence of neutropenia, but may interfere with the efficacy of TMP/SMX. We report a case of P. carinii pneumonia in a patient with AIDS who failed TMP/SMX prophylaxis while taking leucovorin.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Therapy, Combination; Humans; Leucovorin; Male; Pneumocystis; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Nocardia is responsible for infection in both normal and immunocompromised hosts. Organ transplant recipients are increasingly recognized as a sub-group of immunocompromised patients in whom nocardia is an important pathogen. The frequency of nocardia in organ transplant recipients varies between 0.7% and 3%. Nocardia infection has largely been reported in heart, kidney and liver transplant recipients. Presentations of nocardia in lung transplant recipients have been restricted primarily to case reports. The present study reviews the clinical and epidemiologic characteristics of nocardia infection in lung transplant recipients at our institution.. A retrospective cohort study of 473 lung transplant recipients from January 1991 to November 2000 was done at a university hospital. Patient demographics, immunosuppressive regimen at the time of isolation of nocardia species, use of trimethoprim-sulfamethoxazole for Pneumocystis carinii prophylaxis, rejection episodes in the preceding 6 months, concurrent pathogens, site of infection, radiologic findings and treatment and outcome were recorded.. Nocardia infection was found in 2.1% (10 of 473) of our lung transplant recipients. Median time of onset was 34.1 months after transplantation. Nocardia species included N farcinica in 30% (3 of 10), N nova in 30% (3 of 10), N asteroides complex in 30% (3 of 10) and N brasiliensis in 10% (1 of 10) of patients. Post-transplant diabetes was present in 50% (5 of 10) of patients. The primary indication for lung transplantation was emphysema in 40% (4 of 10). Native lung involvement was noted in 75% (3 of 4) of patients with single lung transplant. Breakthrough nocardia infection were noted in 6 patients who were receiving trimethoprim-sulfamethoxazole prophylaxis for P carinii pneumonia; all breakthrough isolates remained susceptible to trimethoprim-sulfamethoxazole. Overall mortality was 40% (4 of 10). All patients (3 of 3) with infection due to N farcinica, except 1 (1 of 7) with infection due to other nocardia species, died. Seventy-five percent (3 of 4) of deaths were attributable to nocardia infection.. Nocardia infection tended to involve the native lung in single lung transplant recipients. Trimethoprim-sulfamethoxazole for P carinii prophylaxis at the doses given was not protective against nocardiosis in these patients. Infection with N farcinica was associated with poor outcome. Thus, species identification and extended courses of antibiotics based on antimicrobial susceptibility testing are important in management of these patients.

Topics: Adult; Anti-Infective Agents; Female; Humans; Lung Transplantation; Male; Middle Aged; Nocardia Infections; Pneumonia, Pneumocystis; Postoperative Complications; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

A retrospective survey was conducted over a 10-year period (1990-99) among 52 haematology divisions in order to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating haematological diseases. The study included 55 patients (18 with non-Hodgkin's lymphoma, 10 with acute lymphoblastic leukaemia, eight with acute myeloid leukaemia, five with chronic myeloid leukaemia, four with chronic lymphocytic leukaemia, four with multiple myeloma, three with myelodysplastic syndrome, two with myelofibrosis and one with thalassemia) who developed PCP. Among these, 18 (33%) underwent stem cell transplantation; only two received an oral prophylaxis with trimethroprim/sulphamethoxazole. Twelve patients (22%) developed PCP despite protective isolation in a laminar airflow room. The most frequent symptoms were: fever (86%), dyspnoea (78%), non-productive cough (71%), thoracic pain (14%) and chills (5%); a severe hypoxaemia was present in 39 patients (71%). Chest radiography or computerized tomography showed interstitial infiltrates in 34 patients (62%), alveolar infiltrates in 12 patients (22%), and alveolar-interstitial infiltrates in nine patients (16%). Bronchoalveolar lavage was diagnostic in 47/48 patients, induced sputum in 9/18 patients and lung biopsy in 3/8 patients. The diagnosis was made in two patients at autopsy. All patients except one started a specific treatment (52 patients trimethroprim/sulphamethoxazole, one pentamidine and one dapsone). Sixteen patients (29%) died of PCP within 30 d of diagnosis. Multivariate analysis showed that prolonged steroid treatment (P < 0.006) and a radiological picture of diffuse lung involvement (P < 0.003) were negative diagnostic factors.

Topics: Acute Disease; Adolescent; Adult; Aged; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Female; Hematologic Neoplasms; Humans; Immunocompromised Host; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Lung; Lymphoma, Non-Hodgkin; Male; Middle Aged; Multiple Myeloma; Multivariate Analysis; Myelodysplastic Syndromes; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Primary Myelofibrosis; Radiography; Retrospective Studies; Thalassemia; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Mutations in the human-derived Pneumocystis carinii dihydropteroate synthase (DHPS) gene have been reported with increasing frequency and have been linked to prior sulfa prophylaxis and possible emergence of sulfa resistance. This study was done to examine the prevalence and clinical significance of P. carinii DHPS mutations in Italian patients. A previously described single-strand conformation polymorphism technique was used to identify P. carinii DHPS mutations in 107 patients with acquired immunodeficiency syndrome. Overall prevalence (8%) was low compared with that in other reports. Mutations were observed in 19% (6/31) of patients exposed to sulfa prophylaxis, compared with 4% (3/76) of patients not exposed to sulfa prophylaxis (P=.017). No significant association was observed between the presence of DHPS mutations and mortality, CD4 cell count, or demographic factors. The study confirms the association between DHPS mutations and prior sulfa prophylaxis and shows that the prevalence of DHPS mutations in an Italian patient population is lower than that in other populations.

Topics: Adult; Aged; Anti-Infective Agents; Bronchoalveolar Lavage; Dihydropteroate Synthase; Female; Humans; Italy; Male; Middle Aged; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Child; Failure to Thrive; Hispanic or Latino; Humans; Immune System Diseases; Infant; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

This study examined polymorphisms in the dihydrofolate reductase (DHFR) gene of Pneumocystis carinii isolates from 27 patients with P. carinii pneumonia (PCP) in Japan. Four substitution sites with two synonymous and two non-synonymous changes were found. Two synonymous substitutions at nucleotide positions 540 and 312 were identified in one and 13 patients, respectively. Two amino acid substitutions (Ala67Val, Cysl66Tyr) were found in two different patients. No linkage of amino acid substitutions in DHFR to those in dihydropteroate synthase was observed. The two patients whose isolates showed non-synonymous DHFR mutations were not exposed to DHFR inhibitors before they developed PCP and were treated successfully with co-trimoxazole.

Topics: Amino Acid Sequence; Anti-Infective Agents; Base Sequence; Bronchoalveolar Lavage Fluid; Dihydropteroate Synthase; Gene Amplification; Genes, Fungal; Humans; Immunocompromised Host; Japan; Molecular Sequence Data; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Polymorphism, Genetic; Sequence Alignment; Sequence Analysis; Tetrahydrofolate Dehydrogenase; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Bacterial Infections; CD4 Antigens; Follow-Up Studies; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

A. Approximately 5% of patients develop Pneumocystis carinii pneumonia (PCP) after renal transplantation if they do not receive prophylaxis. PCP is a severe disease, with a very high fatality rate. Therefore, all renal transplant recipients should receive PCP prophylaxis. The treatment of choice is trimethoprim-sulfamethoxazole (TMP-SMX), at a dose of 80/400 mg/day or 160/800 mg every other day, for at least 4 months. Patients who are treated for rejection should receive TMP-SMX prophylaxis for 3-4 months. B. In the case of TMP-SMX intolerance, aerosolized pentamidine (300 mg once or twice per month) is an alternative for prophylaxis. C. The first-line treatment of PCP is high-dose TMP-SMX. Patients with a PaO2 of <70 mmHg initially should be treated parenterally, and the administration of additional steroids should be considered.

Topics: Anti-Infective Agents; Humans; Kidney Transplantation; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The synthesis and biological properties of a novel water-soluble echinocandin-like lipopeptide, FR131535, are described. This compound displayed potent in vitro and in vivo antifungal activities. The hemolytic activity of FR901379 was reduced by replacing the acyl side chain. This compound showed good water-solubility, comparable to the natural product FR901379.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Bronchogenic Cyst; Candida albicans; Candidiasis; Disease Models, Animal; Echinocandins; Female; Fungal Proteins; Glucosyltransferases; Hemolysis; Membrane Proteins; Mice; Mice, Nude; Peptides; Peptides, Cyclic; Pneumonia, Pneumocystis; Schizosaccharomyces pombe Proteins; Solubility

Topics: Adult; Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Health Planning Guidelines; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Diagnosis, Differential; HIV Infections; Humans; Hypothyroidism; Male; Pneumonia, Pneumocystis; Thyroxine; Trimethoprim, Sulfamethoxazole Drug Combination

Collecting and documenting subjective prior beliefs from knowledgeable clinicians about the potential results of a clinical trial has many advantages. Two large trials of prophylactic treatments in an HIV-positive population are used as examples. The trials recruited patients of primary care physicians and compared treatments which were in use in clinical practice. Opinions about these trials were elicited from 58 practising HIV clinicians. It is shown how the documented opinions can be used to augment the monitoring process; the prior opinions are updated with interim data using approximate Bayesian methods to give posterior opinions incorporating interim results. These posterior opinions can be used by the monitoring board to anticipate the clinicians' reaction to the results. Eliciting prior beliefs is also ethically important for documenting the nature of the uncertainty or equipoise. Important information is provided for the informed consent process and Institutional Review Board (IRB).

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Attitude of Health Personnel; Bayes Theorem; Clinical Trials as Topic; Dapsone; Ethics, Medical; HIV Infections; Humans; Naphthoquinones; Physicians; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Sample Size; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination

Improvement in the immunological and virological profile of HIV-infected population during the era of highly active antiretroviral therapy (HAART), has allowed guidelines on discontinuation of Pneumocystis carinii pneumonia (PCP) prophylaxis to be published. A case of a 37-year-old homosexual man, who had sustained CD4 count over 200 cells/microl for 2 years while on secondary prophylaxis for PCP, who then developed PCP after cessation of prophylaxis, is presented. This case emphasizes the need for close monitoring of patients who discontinued secondary PCP prophylaxis with respiratory symptoms.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Age Factors; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; HIV Infections; HIV-1; Humans; Pneumonia, Pneumocystis; RNA, Viral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; HIV Infections; Humans; Immunocompromised Host; Lymphoma, Non-Hodgkin; Male; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Female; HIV-1; Humans; Long-Term Care; Male; Pneumonia, Pneumocystis; Risk Factors; Sexually Transmitted Diseases, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii (P. carinii) is one of the major opportunistic pathogens responsible for hematopoietic stem cell transplantation (HSCT)-related pneumonias. Although trimethoprim-sulfamethoxazol (TMP/SMX) prophylaxis has been shown to prevent almost all P. carinii infections, 1%-2% of patients may still experience this complication. P. carinii pneumonia (PCP) is usually a late complication in patients receiving TMP/SMX prophylaxis, with most cases occurring later than 2 months post-transplant. We report a patient who developed early onset PCP after allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA-identical sibling donor. On day 12, the patient complained of dyspnea and cough. A chest X ray showed infiltrates in right upper lobe with bilateral pleural effusion. By the findings of Grocott stain on bronchoalveolar lavage fluid obtained on day 14, he was diagnosed as having PCP. Intravenous TMP/SMX failed to improve the lesion. This is the earliest onset PCP in the literature after HSCT despite the prophylactic administration of TMP/SMX before transplant.

Topics: Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Combined Modality Therapy; Cytarabine; Daunorubicin; Etoposide; Fatal Outcome; Hematopoietic Stem Cell Transplantation; Humans; Immune System; Immunocompromised Host; Male; Methotrexate; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Respiratory Insufficiency; Transplantation Conditioning; Transplantation, Autologous; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine; Whole-Body Irradiation

To evaluate the proposed WHO/UNAIDS criteria for initiating co-trimoxazole prophylaxis in adult HIV-infected patients in Africa [WHO clinical stages 2--4 or CD4 count < 500 x 10(6) /l or total lymphocyte count (TLC) equivalent].. Observational cohort study of 5-year follow-up.. Adult HIV clinics, University of Cape Town, South Africa.. Effect of prophylactic low dose co-trimoxazole (480 mg per day or 960 mg three times per week) on survival and morbidity was assessed in patients stratified by WHO clinical stage, CD4 T-lymphocyte count or TLC. Patients receiving antiretroviral therapy were excluded.. Co-trimoxazole reduced mortality [adjusted hazard ratio (AHR), 0.56; 95% confidence interval (CI), 0.33--0.85; P > 0.001] and the incidence of severe HIV-related illnesses (AHR, 0.52; 95% CI, 0.38--0.68; P < 0.001) in patients with evidence of advanced immune suppression on clinical (WHO stages 3 and 4) or laboratory assessment (TLC < 1250 x 10(6)/l or CD4 count < 200 x 10(6)/l). No significant evidence of efficacy was found in patients with WHO stage 2 or CD4 count 200--500 x 10(6)/l/TLC 1250--2000 x 10(6)/l. If we had applied the WHO/UNAIDS recommendations 88.3% of our patients would have received co-trimoxazole prophylaxis at their initial clinic visit.. Co-trimoxazole in HIV-infected adults from an area in which Pneumocystis carinii pneumonia is uncommon demonstrated a survival benefit consistent with previous randomized trials. Further studies are needed to assess the optimal time of commencement of prophylaxis, as widespread co-trimoxazole use will lead to increasing antimicrobial resistance to other major pathogens in Africa.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cohort Studies; Female; Follow-Up Studies; Health Planning Guidelines; Humans; Male; Pneumonia, Pneumocystis; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

Pneumocystis carinii pneumonia (PCP) is a wellknown risk among patients with deficient T-cell function such as children treated for acute lymphoblastic leukemia (ALL). The purpose of this study was to estimate the risk for PCP during maintenance treatment (MT) to identify patients at risk who could benefit from prophylaxis.. We registered all episodes of PCP during MT in 71 children diagnosed between January 1992 and June 1997 with non-B-cell ALL at The Copenhagen University Hospital. Sulphametoxazole and trimetroprim (SMX/TMP) prophylaxis against PCP was given during induction and consolidation therapy but stopped prior to MT with oral methotrexate/6-mercaptopurine. Patients with standard (SR), intermediate (IR), and high risk (HR) ALL started MT at 3, 8, and 15 months from diagnosis, respectively.. The HR group had a cumulated risk of 70% for developing PCP, whereas the risk for PCP in children with IR and the SR was 11 and 8%, respectively (P < 0.0001). All but one of these 13 cases of PCP occurred within 8 months after cessation of SMX-TMP prophylaxis.. The higher incidence of PCP among HR compared to non-HR patients following cessation of SMX/TMP prophylaxis probably reflects the significantly longer T-cell suppressive consolidation therapy in this group. The very low incidence of PCP during the later part of MT emphasizes that methotrexate/6-mercaptopurine MT have more impact on B-cell than on T-cell function. TMP/SMX prophylaxis should be recommended for all children treated for ALL.

Topics: Adolescent; Anti-Infective Agents; Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Denmark; Female; Humans; Incidence; Infant; Lymphocyte Count; Male; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk; T-Lymphocytes; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) is an opportunistic infection associated with increased morbidity and mortality in solid-organ and bone-marrow transplant recipients. Side effects of trimethoprim-sulfamethoxazole (TMP/SMX) are frequent; therefore, we performed a preliminary study using atovaquone suspension, 750 mg once daily, for 1 year for the prevention of PCP in liver transplant recipients intolerant to TMP/SMX therapy. Twenty-eight patients were treated, and data were analyzed for efficacy and toxicity. Adverse events occurred in 14 subjects, mainly related to the gastrointestinal tract. Side effects from TMP/SMX, i.e., rash, completely resolved and bone-marrow suppression improved in 62% of patients. No patients developed Pneumocystis carinii infection. Although a lower dose of atovaquone once daily may be effective in transplant recipients, further studies are necessary to confirm this preliminary observation. Liver Transpl 2001;7:750-751.)

Topics: Antifungal Agents; Atovaquone; Bone Marrow; Drug Eruptions; Humans; Liver Transplantation; Naphthoquinones; Pneumonia, Pneumocystis; Postoperative Care; Prospective Studies; Retreatment; Trimethoprim, Sulfamethoxazole Drug Combination

Two cases of acquired immunodeficiency syndrome with myelodysplasia are presented. Case 1 was admitted because of Pneumocystis carinii pneumonia. Mild anemia, thrombocytopenia and hypersegmented neutrophils were observed. After the administration of trimethoprim-sulfame-thoxazole and antiretroviral therapy, pancytopenia progressed. Bone marrow (BM) showed dysplastic hematopoiesis, suggesting human immunodeficiency virus-myelopathy. Case 2 was hospitalized due to progressive multifocal leukoencephalopathy. BM specimen obtained for thrombocytopenia showed myelodysplasia similar to myelodysplastic syndrome, suggesting that HIV may have an influence on hematopoietic progenitor cells.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bone Marrow; HIV-1; Humans; Male; Myelodysplastic Syndromes; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Investigators have reported that patients infected with Pneumocystis carinii containing mutations in the DHPS (dihydropteroate synthase) gene have a worse outcome than those infected with P carinii containing wild-type DHPS. We investigated patients with HIV-1 infection and P carinii pneumonia to determine if DHPS mutations were associated with poor outcomes in these patients.. We compared presence of mutations at the DHPS locus with survival and response of patients to co-trimoxazole or other drugs.. For patients initially given co-trimoxazole, nine (14%) of 66 with DHPS mutant died, compared with nine (25%) of 36 with wild type (risk ratio50.55 [95% CI=0.24-1.25]; p=0.15). Ten (15%) of 66 patients with a DHPS mutant did not respond to treatment, compared with 13 (36%) of 36 patients with the wild type (0.42 [0.20-0.86]; p=0.02). For patients aged 40 years or older, four (14%) of 29 with the mutant and nine (56%) of 16 with the wild type died (0.25 [0.09-0.67]; p=0.005).. These results, by contrast with those of previous studies, suggest that patients with wild-type P carinii do not have a better outcome than patients with the mutant when given co-trimoxazole. Our results suggest that presence of a DHPS mutation should be only one of several criteria guiding the choice of initial drug treatment of P carinii pneumonia in patients with HIV-1 infection.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dapsone; Dihydropteroate Synthase; Drug Resistance, Microbial; Genotype; HIV-1; Humans; Male; Middle Aged; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Prognosis; Prospective Studies; Survival Analysis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Prophylaxis against Pneumocystis carinii pneumonia (PCP) is an essential part of the management of children with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). No dose-ranging studies were ever performed; therefore, the amount of trimethoprim-sulfamethoxazole (TMP-SMX) needed to suppress PCP in children with HIV/AIDS is not known. The dose recommended by the Centers for Disease Control (CDC) has been thought to be just above the threshold needed for prevention, based on anecdotal breakthrough PCP in cancer patients who were improperly dosed. We have been giving prophylaxis based on body weight rather than surface area, and this, combined with growth of our children, has led to a large experience with dosages lower than the currently recommended 150 mg/m2. The medical records of children with HIV who met CDC guidelines for institution of PCP prophylaxis were reviewed. To ascertain the per square meter (m2) dosage each child was receiving, body surface area was calculated from height and weight measurements. Dosages were recalculated every 6 months and at each dosage change. Data regarding PCP infection, bacterial infections, and side effects of TMP-SMX were extracted. Data were compiled from 1,719.5 child-months of TMP-SMX prophylaxis, including 1,532.5 child-months below the currently recommended dose. Sixty-seven percent of our child-months were at or below two-thirds the CDC recommended dose. There were no cases of proven or suspected PCP. Incidence of other serious bacterial infections was low. Bacteremia and sepsis with Streptococcus pneumoniae was the most common proven bacterial infection, at a rate of 5.5 episodes per 100 child-years. The incidence of bacterial infection did not vary by the dose of TMP-SMX. TMP-SMX prophylaxis was well tolerated; most reactions were mild and self-limited and did not recur with re-institution of the drug. Only 6.1% of this cohort had TMP-SMX prophylaxis discontinued due to perceived toxicity. These data show that the currently recommended dose of TMP-SMX (150 mg/m2) may not be required to prevent PCP in children with HIV/AIDS. The drug is well tolerated at all dosage levels. The incidence of serious bacterial infection in this cohort of patients did not depend upon the amount of TMP-SMX prescribed. A prospective, controlled clinical trial of low-dose TMP-SMX for children with HIV infection is warranted.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Bacterial Infections; Child; Child, Preschool; Female; Humans; Incidence; Male; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Chemoprevention; Drug Administration Schedule; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Child; Female; Humans; Patient Compliance; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii has been recognized as a human pathogen for nearly 50 years. We present a case of P carinii infection that typifies clinical presentation in the era of the acquired immunodeficiency syndrome epidemic. The high incidence of P carinii pneumonia in persons infected with human immunodeficiency virus (HIV) has served to focus laboratory and clinical research efforts on better understanding the biology of the organism and on improving diagnosis, treatment, and prevention of this disease. Although inability to culture P carinii has hampered research efforts, molecular and immunologic approaches have led to the recognition that the organism represents a family of fungi with a very restricted host range and have allowed characterization of clinically relevant antigens and enzymes. Molecular epidemiologic studies have identified more than 50 strains of human-derived P carinii and have suggested that recently acquired infection, as opposed to reactivation of latent infection, may account for many cases of clinical disease. Diagnosis has been improved by the development of organism-specific monoclonal antibodies and, more recently, by polymerase chain reaction using multicopy gene targets, together with induced sputum or oral wash samples. Chemotherapeutic prophylaxis is very effective in preventing P carinii pneumonia; the combination of trimethoprim-sulfamethoxazole remains the first-line agent for both therapy and prophylaxis. Prophylaxis needs to be administered only during periods of high risk; in HIV-infected patients responding to effective antiretroviral therapies, prophylaxis no longer needs to be lifelong. Molecular studies have identified mutations in the target of sulfa drugs that appear to represent emerging resistance in P carinii. Resistance to atovaquone, a second-line agent, may also be developing.

Topics: AIDS-Related Opportunistic Infections; Algorithms; Anti-Infective Agents; Atovaquone; Dihydropteroate Synthase; Drug Resistance, Fungal; Fungal Proteins; Humans; Lymphoma, AIDS-Related; Male; Membrane Glycoproteins; Middle Aged; Mutation; Naphthoquinones; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dihydropteroate Synthase; Drug Resistance, Fungal; Genotype; Humans; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Antibiotic Prophylaxis; Dapsone; Dihydropteroate Synthase; Humans; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Treatment Failure; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Antineoplastic Combined Chemotherapy Protocols; Cough; Diagnosis, Differential; Female; Fever; Humans; Infant; Patient Compliance; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Two hundred eleven adults with human immunodeficiency virus (HIV) infection hospitalized for community-acquired pneumonia, including Pneumocystis carinii pneumonia (PCP; patients), and 192 matched HIV-infected hospitalized patients without pneumonia (controls) were interviewed to determine risk factors for pneumonia. Multivariate logistic regression showed that patients were less likely than controls to have used trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.12-0.41) and more likely to have been hospitalized previously with pneumonia (OR, 6.25; CI, 3.40-11.5). Patients were also more likely than controls to have gardened (OR, 2.24; CI, 1.00-5.02) and to have camped or hiked (OR, 4.95; CI, 1.31-18.7), but stratified analysis by etiologic agent showed this association only for PCP. These findings reconfirm the efficacy of TMP-SMZ in preventing community-acquired pneumonia. In addition, hospitalization for pneumonia might represent a missed opportunity to encourage HIV-infected patients to enter into regular medical care and to adhere to prescribed antiretroviral and prophylaxis medications.

Topics: Adult; Community-Acquired Infections; Female; HIV Infections; Humans; Logistic Models; Male; Middle Aged; Pneumonia; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; CD4 Lymphocyte Count; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Central Nervous System Fungal Infections; Drug Therapy, Combination; Fluconazole; Follow-Up Studies; Homosexuality, Male; Humans; Male; Pneumonia, Pneumocystis; Spinal Puncture; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Administration Schedule; Humans; Patient Compliance; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; beta-Glucans; Female; Glucans; Humans; Immunocompromised Host; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The development of a rash in response to trimethoprim-sulfamethoxazole (TMP-SMX) administration is a frequent adverse reaction in people with the acquired immunodeficiency syndrome (AIDS). In contrast, there are no published reports in the English language literature describing TMP-SMX induced delirium in an AIDS patient. This report describes the development of frank delirium in a person with AIDS receiving TMP-SMX. The episode resolved completely within 72 h of withdrawal of the drug.

Topics: Acute Disease; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Infective Agents; Delirium; Drug Therapy, Combination; Histoplasmosis; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Purine analogs and alkylating agents are the most active drugs in the treatment of patients with chronic lymphocytic leukemia (CLL). Although fludarabine is the most widely tested purine analog in CLL, myelosuppression has limited its use in combination chemotherapy regimens. Because pentostatin (Nipent; SuperGen, San Ramon, CA), a related purine analog with proven activity in CLL, has less myelosuppression, we postulated that it would prove advantageous and could be more readily combined with alkylating agents. We are conducting a phase I/II trial of combination chemotherapy with pentostatin and cyclophosphamide for previously treated patients with CLL. Patients need to have Rai high-risk disease or "active" intermediate-risk disease. The treatment regimen consists of a fixed dose of pentostatin (4 mg/m2) combined with an increasing dose of cyclophosphamide. We plan to treat cohorts of three patients each at cyclophosphamide dose levels of 600, 900, 1,200, 1,500, and 2,000 mg/m2. Cycles will be repeated every 21 days. If unacceptable toxicity is encountered at one dose level, then three additional patients (total of six patients) will be accrued to that dose level before further dose escalations will be permitted. A second instance of unacceptable toxicity will close that dose level and identify the preceding level as the phase II dose. Additional patients will be accrued to the phase II dose level to better assess response. Supportive measures include the use of granulocyte colony-stimulating factor (5 microg/kg/d) to limit neutropenia. Sulfamethoxazole/trimethoprim will be given as prophylaxis against Pneumocystis carinii pneumonia and acyclovir will be administered as prophylaxis for herpes zoster. Response will be assessed according to standard criteria, and flow cytometry and fluorescent in situ hybridization will be used to assess for minimal residual disease in patients with trisomy 12.

Topics: Acyclovir; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Chemoprevention; Chromosomes, Human, Pair 12; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Cohort Studies; Cyclophosphamide; Dose-Response Relationship, Drug; Flow Cytometry; Granulocyte Colony-Stimulating Factor; Herpes Zoster; Humans; Immunosuppressive Agents; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell; Neutropenia; Patient Selection; Pentostatin; Pneumonia, Pneumocystis; Remission Induction; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Trisomy

To assess the incremental cost-effectiveness of 3 Pneumocystis carinii pneumonia (PCP) prophylaxis strategies in patients with Wegener's granulomatosis (WG) receiving immunosuppressive therapies: 1) no prophylaxis; 2) trimethoprim/sulfamethoxazole (TMP/SMX) 160 mg/800 mg 3 times a week, which is discontinued if patients experience an adverse drug reaction (ADR); and 3) TMP/SMX 160 mg/800 mg 3 times a week, which is replaced by monthly aerosolized pentamidine (300 mg) if patients experience an ADR.. A Markov state-transition model was developed to follow a hypothetical cohort of WG patients over their lifetimes starting from the time of initial exposure to the immunosuppressive therapy. The effect of PCP prophylaxis on life expectancy, quality-adjusted life expectancy, average discounted lifetime cost (ADLC), and incremental cost-effectiveness was estimated based on data obtained from a literature review. Direct medical costs were examined from a societal perspective, and costs and benefits were discounted at 3% annually.. No prophylaxis resulted in a life expectancy of 13.36 quality-adjusted life years (QALY) at an ADLC of $4,538. In comparison, prophylaxis with TMP/ SMX alone increased the QALY to 13.54 and was cost saving, with an ADLC of $3,304. The addition of pentamidine in patients who had an ADR to TMP/SMX resulted in 13.61 QALY, with an ADLC of $7,428. Compared with TMP/SMX alone, TMP/SMX followed by pentamidine increased the QALY by 0.07 at an incremental cost of $58,037 per QALY. Both TMP/SMX alone and TMP/SMX followed by pentamidine prophylaxis strategies dominated the no prophylaxis strategy until the incidence of PCP fell below 0.2% and 2.25%, respectively. Institution of pentamidine therapy for patients with a TMP/SMX ADR increased quality-adjusted life expectancy compared with that with TMP/ SMX alone until the incidence of PCP rose above 7.5%.. Prophylaxis using TMP/SMX alone increased life expectancy and reduced cost for patients with WG receiving immunosuppressive therapy. Replacing TMP/SMX with monthly aerosolized pentamidine in cases of ADR further increased life expectancy, although at an increased cost.

Topics: Adult; Anti-Infective Agents; Cost-Benefit Analysis; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Life Expectancy; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A few reports in the medical literature suggest an association between Pneumocystis caring and apnea in small infants. This patient, a 1 month 20 days old, HIV negative, infant girl weighing 2,000 grams was admitted to hospital after presenting a severe episode of apnea with cyanosis and bradycardia. She progressively developed bronchopneumonia by P. carinii that required prolonged mechanical ventilation with high ventilatory parameters. The clinical course of this patient illustrates that apnea can be an early sign of P. carinii infection in small infants. Early diagnosis and specific therapy might prevent morbidity and mortality and also decrease the length of hospitalization.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Apnea; Female; HIV Seronegativity; Humans; Hydrocortisone; Infant; Pneumocystis; Pneumonia, Pneumocystis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

We examined mutations in the dihydropteroate synthase (DHPS) genes of Pneumocystis carinii f. sp. hominis (P. carinii) strains isolated from 24 patients with P. carinii pneumonia (PCP) in Japan. DHPS mutations were identified at amino acid positions 55 and/or 57 in isolates from 6 (25.0%) of 24 patients. The underlying diseases for these six patients were human immunodeficiency virus type 1 infection (n = 4) or malignant lymphoma (n = 2). This frequency was almost the same as those reported in Denmark and the United States. None of the six patients whose isolates had DHPS mutations were recently exposed to sulfa drugs before they developed the current episode of PCP, suggesting that DHPS mutations not only are selected by the pressure of sulfa agents but may be incidentally acquired. Co-trimoxazole treatment failed more frequently in patients whose isolates had DHPS mutations than in those whose isolates had wild-type DHPS (n = 4 [100%] versus n = 2 [11.1%]; P = 0.002). Our results thus suggest that DHPS mutations may contribute to failures of co-trimoxazole treatment for PCP.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Antifungal Agents; Bronchoalveolar Lavage Fluid; Dihydropteroate Synthase; Drug Resistance, Microbial; Female; Genes, Fungal; Humans; Japan; Male; Middle Aged; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Sequence Analysis, DNA; Sulfonamides; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate a strategy for prophylaxis against Pneumocystis carinii pneumonia (PCP) for infants in Thailand.. HIV-infected women were offered trimethoprim-sulfamethoxazole for PCP prophylaxis for their children at 1-2 months of age. When the children reached 6 months of age, investigators simulated a decision to continue or stop prophylaxis on the basis of clinical criteria, and compared their decisions with results of polymerase chain reaction (PCR) testing for HIV. We calculated the proportions of children who received and completed prophylaxis, and compared the rates of pneumonia and death from pneumonia with rates from an earlier prospective cohort.. Of 395 eligible infants, 383 (97%) started prophylaxis. By 6 months of age, 10 (2.6%) were lost to follow-up, three (0.8%) were non-adherent, seven (2%) had stopped because of adverse events, four (1%) had died, and 359 (94%) still received prophylaxis. At 6 months of age, 30 (70%) of 43 HIV-infected children and 16 (5%) of 316 uninfected children met the clinical criteria to continue prophylaxis. The incidence of pneumonia at 1 to 6 months of age was 22% (15/68) in the earlier cohort, and 13% (6/46) in the recent cohort [relative risk (RR) 0.6, 95% confidence interval (CI) 0.3-1.4; P= 0.22]; mortality rates were 9% and 4%, respectively (RR 0.5; 95% CI 0.1-2.3; P = 0.47).. This PCP prophylaxis strategy appeared to be acceptable and safe, may have reduced morbidity and mortality from pneumonia, and should be considered in developing countries where early laboratory diagnosis of perinatal HIV infection is unavailable.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; HIV-1; Humans; Infant; Infectious Disease Transmission, Vertical; Outcome Assessment, Health Care; Pneumonia, Pneumocystis; Prospective Studies; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination

The clinical presentation, diagnosis, histopathologic findings, and elimination of dual respiratory tract infection with Pasteurella pneumotropica and Pneumocystis carinii were studied in 100 adult barrier-reared C.B17 and MRL- lpr mice homozygous for a targeted mutation of the JH region of the immunoglobulin heavy chain.. Necropsy, aerobic bacteriologic culture of hematogenous and pulmonary tissues, histochemical staining of pulmonary tissues, polymerase chain reaction analysis of pulmonary tissues and feces, and viral serologic testing were performed on 19 clinically affected mice and 8 clinically normal mice, then later on antibiotic-treated and caesarian re-derived mice. Therapeutic strategies included sequential administration of trimethoprim/ sulfamethoxazole and enrofloxacin or enrofloxacin administration and caesarian rederivation.. Clinically affected mice had diffuse, nonsuppurative, interstitial pneumonia with superimposed pyogranulomatous lobar pneumonia that was detected microscopically. Affected lung tissue yielded pure culture of P. pneumotropica. Aged-matched, clinically normal mice of both genotypes had interstitial histiocytic pneumonia without lobar pneumonia, and P. pneumotropica was not isolated. Histochemical staining of lung tissues from normal and clinically affected mice revealed scattered cysts consistent with P. carinii, principally in the interstitium. Treatment with sulfamethoxazole/trimethoprim and enrofloxacin eliminated bacteriologic detection of P. pneumotropica, decreased mortality from 50% to 6%, and improved breeding performance.. A successful antibiotic therapy and rederivation approach, incorporating enrofloxacin, cesarian section, and isolator rearing, was developed for B cell-deficient mice with opportunistic infections.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; B-Lymphocytes; Cesarean Section; DNA, Bacterial; Enrofloxacin; Feces; Female; Fluoroquinolones; Immunohistochemistry; Lung; Male; Mice; Mice, Inbred ICR; Pasteurella; Pasteurella Infections; Pneumocystis; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Quinolones; Rodent Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Chemoprevention; HIV Infections; Humans; Patient Compliance; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A knowledge of the epidemiology of Pneumocystis carinii pneumonia (PCP) is important for the development of a strategy for primary PCP prophylaxis and empiric treatment for severe pneumonia in HIV-infected children. However, little is known about the epidemiology of PCP in developing countries. Objective. To measure the relative rate of PCP among hospitalized HIV-infected children with severe pneumonia in Bangkok and evaluate the effect of a strategy of primary PCP prophylaxis in HIV-exposed infants.. All HIV-infected children hospitalized from January, 1996, to December, 1997, for severe pneumonia were investigated for PCP with the use of specimens obtained from bronchoalveolar lavage, endotracheal aspiration or lung tissue necropsy. Characteristics associated with severe pneumonia were described, and the differences between PCP and non-PCP in these severely ill children were analyzed. In June, 1996, a strategy of primary PCP prophylaxis using trimethoprim-sulfamethoxazole in all HIV-exposed infants from 1 to 6 month of age was initiated in our institution. The effect of this strategy was evaluated.. Of 279 hospitalized HIV-infected children 128 (46%) were diagnosed with pneumonia and 26 (20%) of these had severe pneumonia. P. carinii was identified in 9 (35%) children with severe pneumonia. After June, 1996, the rate of severe pneumonia among all hospitalized children decreased from 16% from January through June, 1996, to 7% from July, 1996, through December, 1997 (P = 0.02). Cases of PCP decreased from 9 in 1996 to zero in 1997. The percentage of HIV-infected children receiving PCP prophylaxis at the time of admission increased from 53% before June, 1996, to 72% in late 1997 (P = 0.04). The overall percentage of patients with severe pneumonia receiving PCP prophylaxis at the time of admission was 34%. Breakthrough PCP occurred in 2 children with poor compliance. Patients with PCP were significantly younger than those without PCP (mean age, 10.6+/-10.6 vs. 29.8+/-28.3 months, P = 0.02).. PCP occurred in one-third of cases of severe pneumonia in HIV-infected children in Bangkok. The data suggest that PCP prophylaxis can prevent both PCP and non-PCP.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Child, Preschool; Female; Humans; Infant; Lung; Male; Pneumocystis; Pneumonia, Pneumocystis; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination

To measure the effect of trimethoprim-sulfamethoxazole (TMP-SMX) in preventing bacterial illness, Pneumocystis carinii pneumonia (PCP), and death in people with AIDS, we conducted a retrospective medical record review of 1078 persons who were observed for 3 years on average who attended nine outpatient facilities in Seattle, Washington between January 1990 and April 1996. We calculated relative risk estimates to measure the protective effect of TMP-SMX on the development of major bacterial illnesses, PCP, and death. Use of TMP-SMX decreased the risk of PCP (relative risk [RR] = 0.23; 95% confidence interval [CI], 0.14-0.36) and deaths not attributable to PCP (RR = 0.59; 95% CI, 0.47-0.73). Prevention of major bacterial illnesses of known etiology was of borderline significance (RR = 0.77; 95% CI, 0.57-1.05) and became statistically significant with the addition of patients with infections of unknown etiology (RR = 0.77; 95% CI 0.61-0.97). Use of TMP-SMX PCP prophylaxis significantly reduced the risks of death and of PCP and was associated with a trend toward reduced risk of major bacterial infections.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Bacterial Infections; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; Glucocorticoids; Humans; Male; Methylprednisolone; Pneumonia, Pneumocystis; Prednisone; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To establish the safety and efficacy of desensitization to co-trimoxazole in hypersensitive HIV-infected subjects. To assess if delayed hypersensitivity (type IV) to co-trimoxazole predicts those unable to be desensitized.. desensitization to co-trimoxazole, comprising trimethoprim (T) 0.4 mg and sulphamethoxazole (S) 2 mg initially with doubling dose daily, full strength co-trimoxazole (T/S 160 mg/800 mg) at 10 days. Patch testing with 4.5% and 9% co-trimoxazole in yellow soft paraffin, CMI Multitest.. nineteen patients, 18 male and one female, were recruited and completed the desensitization regime. Of these 80%(15) achieved successful desensitization. Three of those who reacted did so within 18 days. All patients were successfully managed in an outpatient setting. There were no major adverse reactions. Of those reacting none gave a positive patch test to co-trimoxazole and all showed absent delayed type hypersensitivity reactions to recall antigens.. co-trimoxazole desensitization is a safe and efficacious procedure, with a success rate of 80% using the above regime. Patch testing with co-trimoxazole gives no useful information about those that reacted.

Topics: Adult; Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; Female; HIV Infections; Humans; Hypersensitivity, Delayed; Male; Outpatients; Patch Tests; Pneumonia, Pneumocystis; Predictive Value of Tests; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Dapsone; Humans; Pentamidine; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents, Urinary; Antirheumatic Agents; Arthritis, Rheumatoid; Drug Hypersensitivity; Humans; Male; Methotrexate; Middle Aged; Pancytopenia; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A 46-year-old woman developed concurrent CMV and Pneumocystis carinii pneumonia (PCP) 140 days after autologous peripheral blood stem cell transplantation (APBSCT) for AML. She was seropositive for CMV before undergoing APBSCT and had required prednisone for immune thrombocytopenia and allergic dermatitis for 9 weeks prior to the onset of pneumonia. She had also been receiving PCP prophylaxis with pentamidine aerosol every month for 3 months before developing symptoms. The pneumonia was complicated by severe hypoxia, requiring ventilator support and pneumothorax requiring chest tube thoracostomy. She recovered following treatment with trimethoprim-sulfamethoxazole (TMP-SMX), prednisone, gancyclovir and intravenous immunoglobulin. Although the overall incidence of severe CMV disease is low after APBSCT, preventive measures such as surveillance culture and secondary prophylaxis with gancyclovir may be warranted in patients whose cellular immune response is further compromised by corticosteroid use or other factors.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Middle Aged; Pneumonia, Pneumocystis; Pneumonia, Viral; Prednisone; Transplantation, Autologous; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Cortex Hormones; Adult; Clindamycin; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; HIV Infections; Humans; Hydroxylamine; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Ethics, Medical; Fatal Outcome; Female; HIV Infections; HIV-1; Humans; Infant; Infectious Disease Transmission, Vertical; Pneumonia, Pneumocystis; Pregnancy; Pregnancy Complications, Infectious; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Florida; Haiti; Humans; Infant; Infant, Newborn; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To analyse the incidence of Pneumocystis carinii pneumonia after the withdrawal of prophylaxis, in patients with AIDS who were receiving HAART (highly active antiretroviral treatment).. Prospective opened study of 85 patients with AIDS (CD4 lymphocytes < 200 x 10(6)/l) and whose CD4 counts had increased over 200 x 10(6)/l after HAART, 79 were under primary prophylaxis and six secondary.. Mean CD4 lymphocytes count at the time of withdrawal was 343 x 10(6)/l. Mean time of follow-up after withdrawal was 358 days (range: 93-1,487; median: 302). None of the patients have had Pneumocystis carinii or toxoplasmosis after withdrawal of prophylaxis.. Pneumocystis carinii prophylaxis in AIDS patients might be safety withdrawn after effective HAART.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antifungal Agents; CD4 Lymphocyte Count; Female; Humans; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Pyrimethamine; Sulfadiazine; Sulfones; Trimethoprim, Sulfamethoxazole Drug Combination

To characterize clinical, diagnostic and course features of pneumonia caused by Pneumocystis carinii (PC) in hematologic inpatients.. 27 patients with blood diseases were studied. 22 of them had acute respiratory insufficiency and 5 had unclear lung affection. The data from bronchoalveolar lavage (BAL), lung biopsy, serum tests for IgG, IgM anti-PC-antibodies were used for diagnosis of PC-pneumonia.. PC-pneumonia was diagnosed in 8 of 27 patients. Clinical manifestations characteristic for PC-pneumonia were not found. In 5 patients the diagnosis was made on the evidence provided by BAL. Lymphocyte count in BAL was elevated to 27.7 +/- 8.7%. Open biopsy of the lung and transbronchial biopsy diagnosed PC-pneumonia in 2 and 1 patients, respectively. Previous BAL examinations failed to detect PC-pneumonia in 2 of them. In all the patients PC-pneumonia was associated with another infection (bacterial, cytomegaloviral). Histologically, the picture of the disease was determined by the severity of the lung affection or its complications. 5 of 8 patients failed treatment with trimethoprim-sulphamethoxazole and died. Marked respiratory insufficiency was registered at PC-pneumonia diagnosis in all the lethal cases.. Clinical and x-ray pictures of PC-pneumonia in hemoblastosis patients are not specific. All such patients with symptoms of lung infection resistant to antibacterial and antifungal therapy should be examined for PC-pneumonia.

Topics: Acute Disease; Adolescent; Adult; Aged; Anemia, Aplastic; Anemia, Refractory, with Excess of Blasts; Anti-Infective Agents; Biopsy; Bronchoalveolar Lavage Fluid; Female; Hematologic Diseases; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Lung; Lymphoproliferative Disorders; Male; Middle Aged; Multiple Myeloma; Pneumonia, Pneumocystis; Radiography, Thoracic; Respiratory Insufficiency; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Inhalation; Brain Neoplasms; Drug Therapy, Combination; Female; Humans; Infant; Methemoglobinemia; Neuroblastoma; Nitric Oxide; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; China; Drug Eruptions; Drug Hypersensitivity; Female; HIV Infections; Humans; Malaysia; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Scotland; Trimethoprim, Sulfamethoxazole Drug Combination; White People

The aim of this retrospective study was to assess whether corticosteroid adjunctive therapy (CAT) could prevent death in immunocompromised patients with severe Pneumocystis carinii pneumonia (PCP) who do not have human immunodeficiency virus (HIV) infection, similarly to what has been demonstrated for HIV-infected patients. The charts of all non-HIV-infected patients who were admitted to two medical intensive care units between 1988 and 1996 because of severe PCP, defined by an arterial oxygen pressure (determined while the patient was breathing room air) of <70 mm Hg, and who were treated with trimethoprim-sulfamethoxazole were analyzed retrospectively. Thirty-one patients met the study criteria, of whom 23 received CAT (within 72 hours of antibiotic therapy) and eight did not receive CAT. The need for mechanical ventilation (10 [43%] of 23 vs. 4 [50%] of 8) and the mortality rate (9 [39%] of 23 vs. 4 [50%] of 8) were similar for the two groups. Although this small study does not have a statistical power high enough to rule out the possibility of a difference, the results suggest that CAT does not improve the survival of non-HIV-infected patients as has been described for HIV-infected patients with severe PCP.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Humans; Immunocompromised Host; Male; Middle Aged; Pneumonia, Pneumocystis; Reference Values; Retrospective Studies; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used for Pneumocystis carinii pneumonia prophylaxis in human immunodeficiency virus (HIV)-infected patients, but little is known about the effects of this practice on the emergence of TMP-SMX-resistant bacteria. A serial cross-sectional study of resistance to TMP-SMX among all clinical isolates of Staphylococcus aureus and 7 genera of Enterobacteriaceae was performed at San Francisco General Hospital. Resistance among all isolates was <5.5% from 1979 to 1986 but then markedly increased, reaching 20.4% in 1995. This was most prominent in HIV-infected patients: resistance increased from 6.3% in 1988 to 53% in 1995. The largest increases in resistance were in Escherichia coli (24% in 1988 to 74% in 1995) and S. aureus (0% to 48%) obtained from HIV-infected patients. A rapid increase in the use of prophylactic TMP-SMX in HIV disease was also observed during this time in San Francisco and is likely responsible for the increase in TMP-SMX resistance.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Child; Cross-Sectional Studies; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; HIV Infections; Humans; Microbial Sensitivity Tests; Pneumonia, Pneumocystis; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Recent studies of the human Pneumocystis carinii dihydropteroate synthase (DHPS) gene suggest that P. carinii is developing resistance to sulfamethoxazole (SMX) and dapsone. To explore whether P. carinii is also developing resistance to trimethoprim (TMP), the human P. carinii dihydrofolate reductase (DHFR) gene was cloned, DHFR and DHPS genes in 37 P. carinii isolates from 35 patients were sequenced, and the relationship between TMP-SMX or dapsone use and gene mutations was analyzed. The DHFR gene sequences were identical in all isolates except 1 with a synonymous substitution. In contrast, the DHPS gene sequences showed mutations in 16 of the 37 isolates; prior sulfa/sulfone prophylaxis was associated with the presence of these mutations (P<.001). In addition to suggesting that there is less selective pressure on DHFR than on DHPS, this study reinforces the hypothesis that mutations in the DHPS gene are likely involved in the development of sulfa resistance in P. carinii.

Topics: Amino Acid Sequence; Animals; Anti-Infective Agents; Cloning, Molecular; Dapsone; Dihydropteroate Synthase; Drug Resistance, Microbial; Genes, Fungal; Humans; Molecular Sequence Data; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Rats; Sequence Alignment; Sequence Analysis, DNA; Tetrahydrofolate Dehydrogenase; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Anti-Infective Agents; Diagnosis, Differential; Herpesvirus 4, Human; Humans; Infectious Mononucleosis; Male; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination

Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP) is routinely given after allogeneic blood or marrow transplantation. We evaluated the effectiveness of dapsone prophylaxis (50 mg orally twice daily, 3 times per week) compared with twice-weekly trimethoprim-sulfamethoxazole (TMP-SMZ) in preventing PCP after allogeneic blood or marrow transplantation. Patients included all (n=646) who received allogeneic blood or marrow transplants between 1 September 1993 and 31 December 1996 who survived at least 100 days after transplantation. A cohort of 111 dapsone recipients was compared with the remaining 535 who received TMP-SMZ. Ten patients developed PCP; 8 were taking dapsone. PCP incidence in the TMP-SMZ cohort was 0.37% versus 7.2% for dapsone. The relative risk for PCP associated with dapsone use was 18.8 (P<.001) and was not accounted for by age, clinical extensive chronic graft-versus-host disease, donor source, or malignant relapse. Dapsone prophylaxis at this dosage is associated with significantly higher rates of PCP than is TMP-SMZ after allogeneic marrow transplantation. We advise caution in prescribing alternatives to TMP-SMZ prophylaxis in this setting.

Topics: Adult; Anti-Infective Agents; Bone Marrow Transplantation; Clinical Trials as Topic; Cohort Studies; Dapsone; Female; Follow-Up Studies; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Pneumocystis; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Liver Transplantation; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Terbinafine is a synthetic antifungal agent which has recently been found to be highly effective against Pneumocystis carinii. This study evaluated the efficacy of terbinafine on rat P. carinii antigenic profile and the immune response by Western blot analysis, in comparison with atovaquone and co-trimoxazole in rats with pneumocystosis. Terbinafine was shown to target two specific major antigens, particularly those of 116 and 35-40 kDa. Antibodies reactive against these moieties were found in all rats treated with atovaquone and co-trimoxazole, but not in those treated with terbinafine. These surface antigen modifications could be related to disease severity and could provide additional information for monitoring the efficacy of this treatment.

Topics: Animals; Antifungal Agents; Antigens, Fungal; Atovaquone; Blood; Blotting, Western; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Electrophoresis; Immunosuppression Therapy; Male; Naphthalenes; Naphthoquinones; Pneumocystis; Pneumonia, Pneumocystis; Rats; Rats, Sprague-Dawley; Survival Rate; Terbinafine; Trimethoprim, Sulfamethoxazole Drug Combination

Bactrim/Septra is a drug used for treating and preventing PCP (Pneumocystis carinii pneumonia) and toxoplasmosis. However, people with HIV are more likely to develop hypersensitivity reactions to Bactrim/Septra. NAC (N-acetyl-cysteine) is being studied to determine if its detoxifying properties could reduce the risk of hypersensitivity to Bactrim/Septra. However, a Canadian study found no statistically significant difference in the rates of hypersensitivity among the nearly 200 subjects.

Topics: Acetylcysteine; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Hypersensitivity; Free Radical Scavengers; Humans; Pneumonia, Pneumocystis; Primary Prevention; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

The Centers for Disease Control and Prevention (CDC) has determined that HIV-infected people are more likely to become infected first with Pneumocystis carinii pneumonia (PCP) than any other opportunistic infection. About 53 percent of people who died of AIDS between 1992 and 1997 had PCP. The symptoms of the disease are fever, cough, and breathing problems. PCP is thought to be spread through the air - and not through sexual transmission - so it is difficult to prevent exposure. There is no vaccine against PCP, so the most effective treatment is TMP-SMX, a drug which can prevent PCP. The effects and treatment of PCP in adults and children are described, and contact information is provided.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; United States

To evaluate CD4 counts as a predictor of mortality in AIDS patients with respiratory failure due to Pneumocystis carinii pneumonia (PCP).. Retrospective chart review.. Urban university medical center.. Forty-eight patients admitted to the medical ICU from January 1993 to August 1996 with diagnosis of HIV/AIDS, PCP, CD4 count <200 cells per cubic millimeter, who required mechanical ventilation for respiratory failure.. Medical records were reviewed and age, CD4 count, lactate dehydrogenase, room air (RA) PaO2, coinfections, and day of admission to day of intubation (DOA-DOI) data were recorded.. All 48 patients (12 women and 36 men) were treated with corticosteroids and IV trimethoprim-sulfamethoxazole. Age ranged from 21 to 65 years; CD4, 1 to 180, RA PaO2, 27 to 93 mm Hg; and DOA-DOI, 0 to 20 days. Mortality varied significantly depending on CD4 counts: CD4 0 to 10 (100%); CD4 11 to 50 (88%); CD4 51 to 100 (50%); and CD4 >100 (25%). There were no significant difference in mortality between the groups with DOA-DOI <5 days (82%) vs >5 days (80%) or between the groups with PaO2 <60 mm Hg (85%) vs PaO2 >60 mm Hg (73%).. Even though overall mortality was 81%, the mortality rate was significantly different among the four groups. Most striking was the progressive increase in mortality as CD4 cells decreased from >100 (25% mortality) to <10 (100% mortality). Survivors had significantly higher CD4 cell counts than those who died. The CD4 cell count within 2 weeks of admission has significant prognostic value and may be helpful when counseling patients, families, and healthcare surrogates in end-of-life decision making.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Adult; Age Factors; Aged; Anti-Infective Agents; CD4 Lymphocyte Count; Comorbidity; Counseling; Decision Making; Evaluation Studies as Topic; Female; Florida; Forecasting; HIV Infections; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Oxygen; Patient Admission; Pneumonia, Pneumocystis; Prognosis; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; CD4 Lymphocyte Count; Drug Hypersensitivity; Humans; Immunosuppressive Agents; Pneumonia, Pneumocystis; Skin; Trimethoprim, Sulfamethoxazole Drug Combination

An immunosuppressed rat model was used to determine the pharmacokinetics of aerosolized atovaquone (administered with and without a synthetic surfactant) and to evaluate the efficacy of inhaled atovaquone in the prevention and treatment of Pneumocystis carinii pneumonia (PCP). After a single dose by aerosol, mean peak concentrations of atovaquone averaged 52 microg/mL in plasma and 31 microg/g in lungs of rats infected with P. carinii. When atovaquone was combined with surfactant, mean peak concentrations of 94 microg/mL in plasma and 51 microg/g in lung were achieved. Aerosolized synthetic surfactant alone significantly increased survival of rats with PCP and, when combined with atovaquone, increased plasma and lung concentrations of the drug and eradication of the organism.

Topics: Administration, Inhalation; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antifungal Agents; Atovaquone; Dexamethasone; Drug Therapy, Combination; Lung; Male; Naphthoquinones; Pneumonia, Pneumocystis; Pulmonary Surfactants; Rats; Rats, Sprague-Dawley; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Liver Function Tests; Pneumonia, Pneumocystis; Sinusitis; Transaminases; Trimethoprim, Sulfamethoxazole Drug Combination

Sulfamethoxazole is the component of co-trimoxazole responsible for its efficacy against Pneumocystis carinii pneumonia, but this drug is associated with frequent adverse effects. Sulfamethoxypyridazine is significantly more effective than sulfamethoxazole against a murine model of P. carinii and might be a candidate for testing in infected patients.

Topics: Animals; Anti-Infective Agents; Mice; Mice, Inbred BALB C; Pneumonia, Pneumocystis; Rats; Sulfamethoxypyridazine; Trimethoprim, Sulfamethoxazole Drug Combination

This case control study assessed risk factors and prognostic indicators of 350 episodes of bacterial pneumonia in 285 HIV-infected patients. On univariate analysis, intravenous drug abuse (i.v.DA; p < .001 versus controls), regular cigarette smoking (p < .001), cirrhosis (p = .04), and history of a previous episode of pneumonia (p = .04) were risk factors for community-acquired episodes of bacterial pneumonia, whereas length of hospitalization (p = .01) was a risk factor only for nosocomial bacterial pneumonia. The small amount of circulating T CD4+ cells (<100/ mm3) was a risk factor in both groups of pneumonia (p < .05). Stepwise logistic regression analysis revealed that i.v.DA in community-acquired episodes and low levels of circulating T CD4+ cells, both in community-acquired and hospital-acquired episodes, were independent risk factors for the development of bacterial pneumonia. The case-fatality rate observed in our study was 27%. On stepwise logistic regression analysis, T CD4+ cell counts < or = 100/mm3 (p = .02), neutropenia (p = .04), PO2 arterial level < or = 70 mm Hg (p = .01), and Karnofsky score < or = 50 (p = .04) were independent indicators of mortality. According to a personally developed prognostic score, 211 episodes of pneumonia (60%) were classified as mild, 63 (18%) as moderate, and 76 (22%) as severe. Clinicians must carefully evaluate those variables that can influence the prognosis of bacterial pneumonia to make early identification of affected patients and to promptly establish the most appropriate therapeutic strategy in each case.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Case-Control Studies; CD4 Lymphocyte Count; Community-Acquired Infections; Confidence Intervals; Cross Infection; Female; Humans; Karnofsky Performance Status; Length of Stay; Liver Cirrhosis; Logistic Models; Male; Odds Ratio; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Risk Factors; Smoking; Substance Abuse, Intravenous; Survival Analysis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To examine the use of adjunctive corticosteroids in cases of severe Pneumocystis carinii pneumonia (PCP) in non-HIV-infected adult patients.. Retrospective review of medical records.. Tertiary care urban teaching hospital.. Review identified 31 consecutive histologically confirmed primary cases of adult non-HIV-related PCP. Complete records were available for 30 patients, including 20 male and 10 female patients with a mean age of 58.3+/-15 years (+/-SD). Underlying conditions included organ transplantation (n=13), long-term immunosuppressive therapy (n=9), and chemotherapy for malignancy (n=8). All patients had documented PO2 <65 mm Hg or arterial oxygen saturation <90% on room air.. Following the identification of P carinii, in addition to trimethoprim-sulfamethoxazole or pentamidine therapy, 16 patients received increased steroids (> or =60 mg prednisone daily equivalent; increased high-dose steroid group), whereas 14 patients were maintained on a regimen of low doses (< or =30 mg prednisone equivalent daily) or had steroid therapy tapered (low-dose steroid group).. The increased high-dose steroid group demonstrated a shorter required duration for mechanical ventilation (6.3+/-6 days vs 18.0+/-21 days; p=0.047), a shorter duration of ICU admission (8.5+/-7 days vs 15.8+/-8 days; p=0.025), and a shorter duration of supplemental oxygen use (10.0+/-4 vs 32.2+/-33; p=0.05). The hospital duration to discharge for the nine survivors in each group favored the use of corticosteroids (15.4+/-5 days vs 36.3+/-33 days; p=0.077). Similar rates were observed for intubation (75% vs 57%; p=0.442) and in-hospital mortality (44% vs 36%; p=0.722).. These preliminary data suggest that high-dose adjunctive corticosteroids may accelerate recovery in cases of severe adult non-HIV PCP.

Topics: Anti-Infective Agents; Antifungal Agents; Drug Therapy, Combination; Female; Glucocorticoids; HIV Infections; Humans; Intubation, Intratracheal; Male; Middle Aged; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Prednisone; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Some children with perinatal HIV infection develop early progression to severe symptoms (Category C) within the first 4 years of life. Prophylactic therapy with trimethoprim-sulfamethoxazole (TMP/SMX) may affect progression by decreasing the incidence of Pneumocystis carinii pneumonia (PCP).. HIV progression to Category C in the first 3 years of life was retrospectively analyzed in a population-based cohort of children with perinatal HIV infection followed for > or = 3 years from birth. Time to development of Category C and clinical patterns of new Category C diagnoses were examined in relation to patterns of PCP prophylaxis before diagnosis.. Fifty-eight of 147 children developed 67 initial category C diseases by 3 years of age: PCP (n=24), encephalopathy (n=22), other opportunistic infections (n=19) and wasting (n=2). Before diagnosis therapy included TMP/ SMX and zidovudine (ZDV) (n=11), TMP/SMX alone (n=7), ZDV alone (n=1) and neither (n= 39). The probability of developing a Category C diagnosis after 2 years was significantly lower among children who received TMP/SMX compared with those who did not (29%, TMP/SMX vs. 45%, no TMP/SMX; 30%, TMP and ZDV vs. 45%, no therapy; P < 0.01). The frequency of PCP was significantly lower and that of HIV encephalopathy was significantly higher among children receiving TMP/SMX +/- ZDV before Category C diagnosis than among children receiving neither.. In this study PCP prophylaxis was associated with longer time to Category C diagnoses in the first 3 years of life. This association was related to a decreased incidence of PCP and an increased incidence of encephalopathy as the first Category C diagnosis among children who received TMP/SMX.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Anti-HIV Agents; Anti-Infective Agents; Child; Child, Preschool; Cohort Studies; Disease Progression; Female; HIV-1; Humans; Incidence; Infant; Infant, Newborn; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Drug Interactions; HIV Infections; HIV Protease Inhibitors; Humans; Pneumonia, Pneumocystis; Saquinavir; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dihydropteroate Synthase; Drug Resistance, Microbial; Humans; Male; Molecular Sequence Data; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) is a disorder with a very poor prognosis for patients who do not respond to therapy with corticosteroids alone or in combination with immunosuppressive drugs, e.g. cyclophosphamide or azathioprine. For patients with end-stage disease, lung transplantation remains the only possibility for long-term survival. We describe a patient who received a left single lung transplant for end-stage desquamative interstitial pneumonitis. One year later, the patient again began complaining of exertional dyspnoea and a gradual decline in the transfer factor of the lung for carbon monoxide (TL,CO) was apparent. A recurrence of the primary disease in the transplanted lung was suspected on transbronchial biopsies. During treatment with high doses of steroids, a Pneumocystis carinii pneumonia developed, which was treated with co-trimoxazole. The patient completely recovered and, after a period of over 2 yrs, remained in an excellent condition, after which time he was lost from follow-up.

Topics: Adult; Anti-Infective Agents; Glucocorticoids; Humans; Lung Transplantation; Male; Methylprednisolone; Pneumonia, Pneumocystis; Postoperative Complications; Pulmonary Fibrosis; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Opportunistic Infections; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Failures of prophylaxis against Pneumocystis carinii pneumonia (PCP) in AIDS patients do occur, but no evidence for drug resistance has yet been presented.. To determine whether mutations in the sulfa and sulfone drug target are associated with failure of prophylaxis using a sulfa-containing agent.. Portions of the gene for P. carinii dihydropteroate synthase (DHPS), the sulfa and sulfone target, from 27 patients (20 of whom had AIDS) diagnosed with PCP between 1976 and 1997 were amplified using polymerase chain reaction and sequenced. Seven of the 27 patients (all of whom had AIDS) were receiving sulfa or sulfone drugs as prophylaxis for PCP.. Mutations were found at only two amino-acid positions and were significantly more common in patients who received sulfa/sulfone prophylaxis. Mutations were observed in five (71%) out of seven isolates from AIDS patients receiving sulfa/sulfone as prophylaxis compared with only two (15%) out of 13 specimens from AIDS patients who did not (P = 0.022). No mutations were seen in isolates from seven non-HIV-infected patients, none of whom were on prophylaxis. Mutations were only observed in specimens obtained in 1995-1997.. Mutations in two amino-acid positions were significantly more common in AIDS patients with PCP who failed sulfa/sulfone prophylaxis. These amino acids appeared to be directly involved in both substrate and sulfa binding, based on homology to the Escherichia coli DHPS crystal structure. Thus, the results were consistent with the possibility that mutations in the P. carinii DHPS are responsible for some of the failures of sulfa/sulfone prophylaxis in AIDS patients.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Amino Acid Sequence; Anti-Infective Agents; Child; Dapsone; Dihydropteroate Synthase; Drug Resistance, Microbial; Female; Humans; Infant; Male; Middle Aged; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Sequence Analysis, DNA; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Diagnosis, Differential; Drug Eruptions; Drug Therapy, Combination; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Brain Neoplasms; Consciousness Disorders; Disease Susceptibility; Fatal Outcome; Hallucinations; Humans; Lymphoma, AIDS-Related; Male; Pneumonia, Pneumocystis; Psychoses, Substance-Induced; Sulfadiazine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To compare strategies for life-long prophylaxis of Pneumocystis carinii pneumonia (PCP) in a group of AIDS patients with a wide range of disease progression rates.. Markov decision models.. Prophylaxis strategies using high and low doses of trimethoprim-sulfamethoxazole (TS), dapsone, and/or aerosolized pentamidine in sequence, were compared. Efficacy and toxicity rates for prophylaxis regimens were taken from a meta-analysis of pertinent randomized controlled trials. Outcomes measured included lifetime episodes of PCP and drug toxicity per 100 patients treated, average life expectancy, and cost.. For patients with an expected survival of 3 years after commencement of prophylaxis, the use of standard or low dose TS as the first choice agent was comparable, and both were superior to the other strategies for preventing PCP (between nine and 26 fewer episodes of PCP per 100 patients treated) though they were more toxic (11-44 more episodes of toxicity per 100 patients treated). Life expectancy was similar for all of the treatment strategies. With slower rates of disease progression (expected survival > 3.8 years), as seen with current antiretroviral regimens, the use of low dose TS as the first choice agent dominated the use of standard dose TS; when the expected survival time was 7 years, initial use of low dose TS led to 2.8 fewer episodes of PCP per 100 patients treated, 32 fewer episodes of toxicity per 100 patients treated, and US$1381 per patient lower cost, compared with prophylaxis with standard dose TS.. For patients with AIDS and expected survival > 3.8 years, low dose TS is better than standard dose TS as the first choice agent for preventing PCP. As patients with AIDS live longer, the routine use of low dose TS will be more than adequate for patients at risk for PCP.

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Disease Progression; Drug Costs; Health Care Costs; Humans; Life Expectancy; Markov Chains; Pneumonia, Pneumocystis; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

We report a case of Pneumocystis carinii pneumonia in a patient with acquired immunodeficiency syndrome diagnosed and monitored with polymerase chain reaction (PCR) for Pneumocystis carinii on sputum and measurement of plasma (1-->3)-beta-D-glucan (G-test). Results of both studies paralleled the clinical and radiographic improvement. However, the plasma (1-->3)-beta-D-glucan level remained higher than normal when PCR for Pneumocystis carinii became negative in sputum. Both PCR for Pneumocystis carinii on sputum and measurement of plasma (1-->3)-beta-D-glucan are useful for noninvasive diagnosis and monitoring of Pneumocystis carinii, although further investigation is necessary to quantify their relationship.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; beta-Glucans; Glucans; Glucocorticoids; Humans; Male; Methylprednisolone; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Radiography, Thoracic; Sputum; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) occurs commonly in immunocompromised patients. Sulfamethoxazole-trimethoprim (SMX-TMP) is effective prophylaxis, although PCP may still occur despite apparently adequate use. We report three cases of PCP which highlight some of the pitfalls of prophylaxis.

Topics: Anti-Infective Agents; Child; Female; Humans; Immunocompromised Host; Infant; Male; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) remains the most frequently reported serious opportunistic infection in AIDS patients and the second highest cause of mortality among persons with AIDS in the United States, despite the availability of effective chemoprophylaxis.. To evaluate incidence of PCP and determinants of PCP chemoprophylaxis failure, we analyzed data from 2842 patients visits to infectious diseases physicians at 10 HIV clinics (eight private and two public) in eight U.S. cities from January 1992 through June 1996 as part of the HIV Outpatient Study (HOPS). We performed a time-dependent regression analysis to examine potential determinants of PCP chemoprophylaxis failure.. The incidence of chemoprophylaxis failure was 4.6 PCP cases/100 person-years on chemoprophylaxis; these cases represent 67% of all incident episodes of PCP. In a multivariate analysis, the only significant predictors of chemoprophylaxis failure were the use of agents other than trimethoprim-sulfamethoxazole (TMP-SMX), history of prior PCP, and a CD4+ T-lymphocyte cell count of <50 cells/microl. Dosing or frequency of TMP-SMX did not seem to influence risk of chemoprophylaxis failure.. Chemoprophylaxis failure, especially among those with the most advanced immunosuppression or history of prior PCP, was the most significant source of new PCP cases in the HOPS cohort and thus represents one of the largest contributors to morbidity and mortality in this cohort.

Topics: Adult; AIDS-Related Opportunistic Infections; Ambulatory Care; Anti-Infective Agents; Antifungal Agents; Atovaquone; Cohort Studies; Dapsone; Drug Therapy, Combination; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Morbidity; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: Aged; Anti-Infective Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Asbestosis; Bronchoalveolar Lavage Fluid; Fatal Outcome; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Methotrexate; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To describe the epidemiological characteristics of toxoplasmic encephalitis in HIV-infected patients with a more than 12-year follow-up.. From a data base of 1,628 AIDS subjects hospitalized from 1983 to 1994, we studied the epidemiological characteristics of 399 patients with toxoplasmic encephalitis. Diagnosis of toxoplasmic encephalitis was based on the association of central neurological disorders, typical lesions on CT scan or MRI, and favorable outcome under appropriate toxoplasmosis therapy.. Four hundred sixty-four cases of toxoplasmic encephalitis were reported in 399 patients (24.5% of the patients with AIDS). The overall incidence was 20.5 per 100 patients-year. Toxoplasmic encephalitis was the first AIDS defining event in 51% of the cases and revealed HIV infection in 13% of the cases. In the remaining 49%, the mean delay from AIDS diagnosis to toxoplasmic encephalitis was 13 months (range: 1-71 months). At the time of diagnosis, mean CD4 count was 44/mm3 (range: 0-408/mm3). Antibodies to Toxoplasma gondii were found in 97% of the cases. Before the first episode of toxoplasmic encephalitis, 58% of the patients were given antiretroviral therapy (mean: 17.8 months; range: 1-64 months). Of the 399 patients with toxoplasmic encephalitis, 366 (92%) did not receive any primary toxoplasmosis prophylaxis. Among them, 205 (56%) did not receive any drug prophylaxis, and 161 (44%) had Pneumocystis carinii pneumonia prophylaxis alone (aerosolized pentamidine). Thirty-three failures were observed (8%) with cotrimoxazole: 14 cases (3%) were considered to have irregular compliance. Sixty-five relapses were observed in 52 patients. At the end of the study 334 patients had died (84%). The median survival was 11.4 months (95% confidence interval, range: 10.4-12.4 months).. Toxoplasmic encephalitis incidence has decreased since the introduction of appropriate drug prophylaxis.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antibodies, Protozoan; Antifungal Agents; Antiviral Agents; CD4 Lymphocyte Count; Chemoprevention; Coccidiostats; Databases as Topic; Female; Follow-Up Studies; France; HIV Infections; Humans; Incidence; Magnetic Resonance Imaging; Male; Pentamidine; Pneumonia, Pneumocystis; Recurrence; Survival Rate; Time Factors; Tomography, X-Ray Computed; Toxoplasma; Toxoplasmosis, Cerebral; Treatment Failure; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To monitor trimethoprim and sulfamethoxazole plasma levels in patients with AIDS-associated Pneumocystis carinii pneumonia.. Trimethoprim-sulfamethoxazole steady-state plasma concentrations were measured by high-pressure liquid chromatography during 37 episodes of Pneumocystis carinii pneumonia in patients with AIDS. Initially, 15-23 mg/kg/day trimethoprim and 75-115 mg/kg/day sulfamethoxazole were given i.v. Assuming a therapeutic range for trimethoprim from 4 to 10 microg/ml, the doses were adjusted if trimethoprim levels were found to be outside this range.. Mean concentrations were 6.7+/-3.3 g/ml for trimethoprim and 187+/-56 microg/ml for sulfamethoxazole. A widespread inter-patient range was found and could be decreased after dose adjustment. Enzyme inducing co-medication did not influence plasma concentrations. In patients with coexisting chronic liver disease, significantly increased sulfamethoxazole plasma levels were observed. A correlation could be demonstrated between serum creatinine and trimethoprim plasma levels. Adverse reactions associated with co-trimoxazole occurred during 65% of treatment periods and increased with increasing trimethoprim-sulfamethoxazole levels, as well as increasing length of treatment. Therapy only had to be prematurely discontinued in one patient. Overall mortality was 2.7%. Monitoring of co-trimoxazole levels during the treatment of P. carinii pneumonia in AIDS may help in reducing the high variability of plasma-concentrations and in avoiding severe side-effects especially associated in patients with chronic liver disease or renal failure.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chromatography, High Pressure Liquid; Chronic Disease; Drug Monitoring; Female; Humans; Kidney; Liver Diseases; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

In this paper, the authors present an evaluation algorithm for systematic assessment of the observed heterogeneity in disease risk within trial populations. Predictive models are used to estimate the predicted patient hazards, the odds of having an event in the upper risk quartile (ODU) and the lower risk quartile (ODL), and the odds ratio (rate ratio for time-to-event analyses) for having an event in the upper risk quartile versus the lower risk quartile (extreme quartile odds ratio (EQuOR) and extreme quartile rate ratio (EQuRR)). The ranges for these metrics depend on the extent to which predictors of the outcome of interest exist and are known and the extent to which data are collected in the trial, as well as on the eligibility criteria and the specific patients who are actually enrolled. ODU, ODL, and EQuOR values are used to systematically interpret the results for patients at different levels of risk, to evaluate generalizability, and to determine the need for subgroup analyses. Individual data for five outcomes from three trials (n = 842, 913, and 1,001, respectively) are used as examples. Observed EQuOR values ranged from 1.5 (very little predicted heterogeneity) to 59 (large heterogeneity). EQuRR values ranged from 2 to 46. ODU values ranged from 0.24 to 3.19 (generally high risk), and ODL values ranged from 0.01 (clinically negligible risk) to 0.16 (clinically meaningful risk). The algorithm may also be used for comparing diverse trials (e.g., in meta-analyses) and used prospectively for designing future trials, as shown in simulations.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Algorithms; Anti-HIV Agents; Bias; Dapsone; Humans; Meta-Analysis as Topic; Models, Statistical; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Research Design; Risk; Survival Analysis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

To report a case of successful desensitization to dapsone for Pneumocystis carinii pneumonia (PCP) prophylaxis in a patient unable to tolerate trimethoprim/sulfamethoxazole (TMP/SMX) desensitization or dapsone at standard doses.. A 37-year-old HIV-positive African-American man was treated for pneumonia with TMP/SMX and then continued on the drug for PCP prophylaxis. After experiencing a pruritic maculopapular rash with TMP/SMX, both at standard doses and after attempting a desensitization regimen to the drug, he was started on dapsone for PCP prophylaxis. He experienced a rash and fever after taking dapsone at standard PCP prophylactic doses. At this time, an 18-day oral dapsone rechallenge by dose escalation was attempted, and it was well tolerated.. This case suggests that utilization of a dapsone desensitization regimen may permit a viable treatment option in patients previously thought to be intolerant to the agent. More regimens of this type should be attempted and the results published, using both dapsone and TMP/SMX, so that standard desensitization treatment guidelines may eventually be adopted.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dapsone; Desensitization, Immunologic; Drug Hypersensitivity; HIV Seropositivity; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Besides Pneumocystis carinii bacterial pathogens represent the most common aetiology of pulmonary infections in HIV-positive patients. However, the impact of PCP prophylaxis on the incidence of bacterial pneumonia in HIV-positive patients using pentamidine or co-trimoxazole is still unknown.. We analysed retrospectively the data of 80 consecutive HIV-positive patients with a CD4-cell count < 300/microliter. The total observation period was 1993 patient months. Type and duration of chemoprophylaxis, frequency of bacterial pneumonia, PCP, extrapulmonary bacterial infections and cerebral toxoplasmosis were documented in a standardised manner. For statistical analysis we used the Kaplan-Meier test for the time to a recurrence of the various infections under both prophylaxis regimens and the Odds ratio for determination of the relative risk.. We followed up 47 patients inhaling 300 mg pentamidine monthly for a total of 1133 months and 33 patients taking 480 mg co-trimoxazole per day p.o. for a total of 860 months. There were no statistically significant differences between the two groups in respect of demographic parameters, stage and therapy of HIV infection and distribution of risk groups. We found seven bacterial pneumonias in the co-trimoxazole group and 13 in the pentamidine group (not significant); the most common causative organisms were S. pneumoniae (n = 4), S. aureus (n = 3) and H. influenzae (n = 3). Furthermore, in the pentamidine group 12 PCP and nine cases of toxoplasma encephalitis were observed, whereas none of these infections occurred in the co-trimoxazole group (p < 0.05). Two of the patients taking co-trimoxazole and 15 of those inhaling pentamidine had extrapulmonary bacterial infections (p < 0.05), the most frequently identified pathogen being S. aureus (n = 7). The two prophylaxis groups did not differ significantly with regard to laboratory data, course and therapy of the bacterial pneumonias.. There was no significant influence of chemoprophylaxis on the incidence of bacterial pneumonia in patients with advanced HIV-disease in our study. Since S. pneumoniae represents the most common causative agent, we suggest immunisation with a polyvalent pneumococcal vaccine at an early stage of HIV-infection.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; CD4 Lymphocyte Count; Female; Humans; Male; Middle Aged; Odds Ratio; Pentamidine; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Retrospective Studies; Risk; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Drug-induced hyperkalemia is an important but often overlooked problem encountered commonly in clinical practice. It may occur in the ambulatory as well as the impatient setting. Every evaluation of a hyperkalemic patient should include a careful review of medications to determine if a drug capable of causing or aggravating hyperkalemia is present. Medications generally produce hyperkalemia either by causing redistribution of potassium (beta2 -adrenergic blockers, succinylcholine, digitalis overdose, hypertonic mannitol) or by impairing renal potassium excretion. Drugs cause impaired renal potassium excretion by (1) interfering with the production and/or secretion of aldosterone (nonsterodial anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, heparin, cyclosporine, and FK 506) or (2) blocking the kaliuretic effects of aldosterone (potassium-sparing diuretics, trimethoprim, pentamidine, and nefamostat mesilate). Because severe renal insufficeiency is generally required to cause hyperkalemia, an elevated serum potassium concentration in a patient with mild-to-moderate renal failure should not be ascribed to renal failure alone. A careful search for "hidden" potassium loads and for causes of impaired tubular secretion of potassium (including drugs) is necessary. Finally, it is important to recognize that the causes of hyperkalemia may be additive. Patients may have more than one cause of hyperkalemia at the same time. Therefore, all potential causes of hyperkalemia, including drugs, should be systematically evaluated in every hyperkalemic patient.

Topics: Adult; AIDS-Related Opportunistic Infections; Aldosterone; Anti-Infective Agents; Diagnosis, Differential; Electrocardiography; Fluid Shifts; Humans; Hyperkalemia; Male; Pneumonia, Pneumocystis; Potassium; Tissue Distribution; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Pneumonia, Pneumocystis; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

Complicated regimens can lead to adherence problems when they include protease inhibitors and anti-PCP medications. A study of 244 adults showed that adherence was not a factor of age, race, gender, or class but was related to the number of times per day a medication was taken, the belief that the medications would work, the patient's positive mental health, and whether friends or family members would remind patients about taking their medications. Researchers need to address adherence issues in an effort to stop the development of drug resistant viruses.

Topics: AIDS-Related Opportunistic Infections; Dapsone; Humans; Patient Compliance; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Three studies that are highlighted suggest that PCP-causing microbes are developing resistance to Bactrim/Septra (B/S), the drug of choice for preventing the life-threatening complications caused by PCP, toxoplasmosis, and bacterial pneumonia. While resistance does not appear to be happening on a large scale, it is a concern because no other drug has the same beneficial effects of B/S. Research is needed for simple, low-toxicity treatments and prophylactic drugs for PCP, before resistance becomes a common problem.

Topics: AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Drug Resistance, Microbial; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Using results of a multicentric randomized prospective trial of primary prophylaxis of Pneumocystis carinii pneumonia in HIV-infected patients which compared sulfamethoxazole-trimethoprim and pentamidine isethionate, the risk to develop cerebral toxoplasmosis was analyzed in the two assigned groups and in the groups of patients who stopped sulfamethoxazole-trimethoprim prophylaxis. The risk to develop cerebral toxoplasmosis appeared significantly higher in the group of patients who stopped sulfamethoxazole-trimethoprim consecutively to cutaneous hypersensitivity.

Topics: AIDS-Related Opportunistic Infections; Drug Eruptions; Drug Therapy, Combination; Follow-Up Studies; Humans; Multicenter Studies as Topic; Pentamidine; Pneumonia, Pneumocystis; Probability; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Survival Rate; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Tremor; Trimethoprim, Sulfamethoxazole Drug Combination

The records of patients in whom Pneumocystis carinii pneumonia (PCP) was diagnosed between January 1989 and December 1991 were reviewed. Thirty-two patients--all immunocompromised--were included in the study: 41% were HIV-positive and 59% HIV-negative. In 23 patients (72%) concomitant pathogens were isolated, most frequently Cytomegalovirus. Presenting symptoms included fever (97%), cough (75%) and dyspnea (63%). All HIV-infected patients had a T4-lymphocyte count below 200/mm3 (or 20%). The majority of patients (80%) treated with trimethoprim-sulfamethoxazole experienced adverse events which were usually well tolerated so that a therapy change was necessary in only 12% of patients. PCP was fatal in 34% of the patients. Respiratory failure requiring mechanical ventilation carries a poor prognosis. The ratio of non-AIDS/AIDS patients infected with PC is increasing. This increase is due to the growing contribution of patients treated with immunosuppressive agents and patients with disease-associated immunodeficiencies other than AIDS. Our study suggests that treatment of PCP is more successful with early diagnosis. In addition, as mortality rate is high in non-AIDS patients, our data suggest that the more frequent use of PCP prophylaxis in patients given immunosuppressive drugs, might reduce the incidence of PCP and PCP related mortality.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; HIV Seropositivity; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Pneumonia, Pneumocystis; Prognosis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the influence of empiric treatments prior to fiberoptic bronchoscopy (FOB) on the diagnostic yield of BAL in HIV-positive patients with respiratory symptoms.. We studied 123 consecutive FOBs with BAL in HIV-positive patients; 101 of these patients (82%) had received previous antimicrobial treatment from 1 to 60 days. Diagnostic yield of BAL for Pneumocystis carinii, Mycobacterium tuberculosis, and bacterial pneumonia was compared between patients with and without previous empiric treatments.. A diagnosis was obtained in 85 patients (69%), of whom 17 (20%) had multiple infections. Diagnostic yield was higher in patients without previous treatment, 91% (20/22) compared with 64% (65/101), p < 0.03. Diagnostic yield was also higher for bacterial pneumonia: seven isolations from 22 patients not receiving previous empiric treatment (32%), compared with 11 of those who had (11%; p < 0.02). The duration of empiric treatment against P carinii in patients in whom it was isolated was significantly shorter than in those in whom P carinii was not detected (3.5 +/- 1.8 days compared with 5.2 +/- 2.4 days; p = 0.003). FOB permitted a change in treatment in 62% of patients with a final diagnosis.. This study demonstrates that empiric treatments prior to FOB significantly impair the diagnostic yield of BAL in detecting common pathogens in HIV-infected patients with respiratory symptoms.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antitubercular Agents; Bacteria; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cytomegalovirus; Cytomegalovirus Infections; Female; Fiber Optic Technology; Herpes Simplex; Humans; Length of Stay; Lung Diseases; Male; Middle Aged; Mycobacterium tuberculosis; Pentamidine; Pneumocystis; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Simplexvirus; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Adverse drug reactions to trimethoprim-sulfamethoxazole (TMP/SMX) are common in HIV-positive patients. However, only one case of TMP/SMX-related rhabdomyolysis has been reported, so far. We report a 55-year old-man with asymptomatic rhabdomyolysis after oral high-dose TMP/SMX for suspected PCP. Laboratory changes settled after discontinuation of the drug.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Rhabdomyolysis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Clinical Trials as Topic; Dapsone; Data Collection; Data Interpretation, Statistical; Databases, Bibliographic; Humans; Information Storage and Retrieval; Meta-Analysis as Topic; Multivariate Analysis; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Selection Bias; Trimethoprim, Sulfamethoxazole Drug Combination

Adolescents infected with the human immunodeficiency virus (HIV) often confront the clinician with difficult medical problems. Besides the host of opportunistic infections, which can affect these patients, side effects from medications can be frequent and, at times, life-threatening. We report a case of aseptic meningitis secondary to trimethoprim-sulfamethoxazole therapy for prophylaxis against Pneumocystis carinii in an HIV-infected adolescent.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Anti-Infective Agents; HIV Seropositivity; Humans; Male; Meningitis, Aseptic; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A population pharmacokinetic model of intravenously and orally administered trimethoprim in patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia has been made using a parametric iterative two-stage Bayesian and a nonparametric expectation maximization computer program. When good information was present in the serum level data, both methods obtained similar results. With the nonparametric expectation maximization program, the median apparent rate constant for absorption (Ka) was 1.602 hr-1, median slope (Ks) of the relationship between creatinine clearance and elimination was 0.001168 hr-1, median apparent volume of distribution (Vs) was 1.058 l/kg, and median fraction of oral dose absorbed (Fa) was 0.955. These results permit dosage individualization adjusted to body weight and renal function to achieve chosen serum level peak and trough goals. Peak goals of 9 ug/ml and trough goals of 5 ug/ml appear reasonable for most patients in this population, and should permit most to complete an effective course of therapy with a reduced risk for treatment-terminating hematologic toxicity. However, therapeutic goals should always be selected based on each patient's apparent need for the drug and the risk of toxicity that is justifiably acceptable to obtain the expected benefits of the drug.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bayes Theorem; Drug Monitoring; Humans; Injections, Intravenous; Models, Biological; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Bone Marrow Transplantation; Drug Resistance, Microbial; Enterococcus faecalis; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Drug Therapy, Combination; Humans; Hyperglycemia; Methylprednisolone; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acetylation; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; Humans; Male; Middle Aged; Phenotype; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Desensitization, Immunologic; Drug Eruptions; Humans; Male; Pneumonia, Pneumocystis; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

The estate of [name removed] will receive a $75,000 emotional distress award in addition to $104,109 in emotional damages from Dr. [name removed], [name removed], an infectious disease specialist. [Name removed] suffered an allergic reaction to Cotrim, a sulfa-based medicine prescribed by Dr. [name removed]. The reaction resulted in [name removed]'s hospitalization and eight months of recovery. [Name removed]'s allergy to sulfa-based drugs was noted on his chart. [Name removed]'s attorney argued that [name removed] was already in a frail emotional state and thus should not be entitled to full recovery of emotional distress damages. In 1995, the State Court of Appeals ruled that the damage award should go back to court. The Supreme Court turned down [name removed]'s request and restored the damage award.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Hypersensitivity; Fluoroquinolones; Humans; Male; Malpractice; Medical Records; Oregon; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Research results to determine the best prophylactic regimen for Pneumocystis carinii pneumonia (PCP) are reported. Overall results from these studies indicate patients who are eligible for PCP prophylaxis should be advised to take double-strength trimethoprim/sulfamethoxazole (TMP/SMX) on a daily basis, a dosage found more effective than thrice-weekly. To handle problems with side effects, one study demonstrated the success of using a 6-day dose escalation method that allowed 80 percent of the participants to complete treatment for 6 months. Patients remaining intolerant to TMP/SMX have the options of using atovaquone (not yet FDA-approved for PCP prophylaxis) or aerosolized pentamidine (not approved for treatment of PCP), which have been shown to be safe and effective in PCP prophylaxis. Due to recent FDA reforms, the use of off-label drugs may increase, but patients and physicians are cautioned that problems with insurance reimbursement may develop.

Topics: Aerosols; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; CD4 Lymphocyte Count; Clinical Trials as Topic; Dapsone; Drug Administration Schedule; Encephalitis; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the effectiveness of primary prophylaxis in preventing Pneumocystis carinii pneumonia (PCP) in children with perinatally acquired human immunodeficiency virus 1 (HIV-1) infection.. We conducted a retrospective analysis of a cohort of infants followed from birth at six metropolitan hospitals and one outpatient clinic for pregnant, drug-using women in New York City. Outcomes measured were histologically confirmed PCP and/or death. The potential confounding effect of the infant's stage of illness, as determined by CD4 count, was controlled by including all CD4 determinations as time-dependant covariates in a Cox proportional hazards analysis. Cases were censored at PCP onset, death, loss to follow-up, and 18 months of age.. One hundred twelve HIV-infected children were enrolled at birth between 1986 and 1993. Sixty of these were tracked beyond 18 months of age; of the others, 21 died before this age, 4 were considered lost to follow-up, and 27 had not reached 18 months of age at the last visit. Only 3 cases (4%) of confirmed PCP occurred among the 70 children who received primary PCP prophylaxis before 18 months of age, compared with 12 cases (28%) among 42 children not receiving PCP prophylaxis at any point before 18 months of age. The Kaplan-Meier estimated incidence of PCP in the first year among children not receiving prophylaxis was 25% (95% confidence interval [CI], 12 to 39). Using Cox methods, the unadjusted risk of PCP among infants not receiving prophylaxis, relative to those receiving it, was 4.1 (95% CI, 1.1 to 15); the relative risk was 4.4 (95% CI, 1.2 to 17) adjusting for the percentage of CD4-positive lymphocytes and 5.1 (95% CI, 1.3 to 20) adjusting for the absolute number of CD4-positive cells. Eight of 26 deaths were caused by PCP, and the likelihood of early death was significantly diminished if PCP prophylaxis was given (relative risk controlling for absolute CD4 cells, 2.57; 95% CI, 1.1 to 6.1).. We report evidence that primary antimicrobial PCP prophylaxis is highly effective in decreasing the frequency of PCP and early death in infants with perinatal HIV infection. These findings support the revised National Pediatric HIV Resource Center and Centers for Disease Control and Prevention guidelines for PCP prophylaxis in children.

Topics: Acquired Immunodeficiency Syndrome; Age Factors; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Female; Follow-Up Studies; Humans; Incidence; Infant; Pneumonia, Pneumocystis; Pregnancy; Primary Prevention; Proportional Hazards Models; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aclarubicin; Acute Disease; Adult; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cohort Studies; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Etoposide; Female; Finland; Humans; Immunocompromised Host; Incidence; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Mitoxantrone; Pneumonia, Pneumocystis; Prednisone; Premedication; Retrospective Studies; Thioguanine; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

To examine the safety and efficacy of aerosolized pentamidine (AP) as alternative primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in adult liver and kidney transplant recipients.. Retrospective review of medical records.. Tertiary care urban teaching hospital with active liver and kidney transplant programs.. Adult liver and kidney transplant recipients intolerant of trimethoprim-sulfamethoxazole (TMP-SMX) therapy and referred to the AP clinic between June 1991 and December 1994.. Each patient received monthly AP, 300 mg, delivered by a nebulizer (Respirgard-II), preceded by inhaled albuterol, 180 micrograms. During the period of follow-up, information related to side effects of AP and incidence of PCP was recorded.. A total of 35 patients were identified, 18 liver and 17 kidney transplant recipients. Fourteen patients received AP as initial prophylaxis because of prior sensitivity to TMP-SMX. In another 19 patients, initial TMP-SMX therapy was discontinued for leukopenia (5), elevated liver function test values (4), rash (3), nausea (2), renal failure (2), seizure (2), and thrombocytopenia (1). In addition, two patients received AP in the setting of organ rejection. Liver transplant recipients received AP for an average of 4.28 +/- 1.6 months, and renal transplant recipients received AP for an average of 5.71 +/- 4.3 months. Adverse effects of AP included bronchospasm (two), dyspnea (one), cough (one), and nausea (one). AP therapy was discontinued in only one patient due to severe bronchospasm. There were no cases of PCP in the 35 patients receiving AP.. These observations suggest that AP is well tolerated and may be an effective alternative for PCP prophylaxis in adult liver and kidney transplant recipients intolerant to TMP-SMX therapy.

Topics: Adult; Aerosols; Anti-Infective Agents; Antiprotozoal Agents; Female; Humans; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Dapsone; Drug Therapy, Combination; Humans; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Graft Rejection; Humans; Imipenem; Kidney Transplantation; Lung; Lung Diseases; Male; Middle Aged; Nocardia asteroides; Nocardia Infections; Opportunistic Infections; Pneumocystis; Pneumonia, Pneumocystis; Risk Factors; Thienamycins; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Eighty initial episodes of HIV-associated Pneumocystis carinii pneumonia (PCP) diagnosed at Bordeaux hospital between 1985 and 1993 are reported (57 were men and 23 women). PCP revealed HIV infection in 29 patients (36%). Others cases were patients with poor medical follow up (10%), with a CD4+ lymphocyte count above 200/mm3 at last follow-up (9%), non compliant with PCP prophylaxis (9%), or using aerolized pentamidine (AP+) (20%). The main clinical symptoms were fever (90%), dyspnea (68%), non productive (63%) and productive (17%) cough. Radiographic infiltrates were purely interstitial (59%), acinar and interstitial (25%), purely acinar (5%) and absent (11%). Thirty-eight percent of AP+ had upper lobe preferential involvement and 13% a pleural effusion. In all cases, Pneumocystis carinii was detected in bronchoalveolar lavage. Extrapulmonary localizations of pneumocystosis were noticed (eye, liver, spleen, ascitis) in two AP+. Mean CD4+ count was 54/mm3 in patients not having received aerolized pentamidine (AP-) and 22/mm3 in AP+. P24 antigenemia was positive in 53% (AP-) and 88% (AP+). PaO2 LDH and albuminemia were similar in both groups. Antimicrobial therapy (Cotrimoxazole in 91% of the cases) was combined with corticosteroids in 45% and mechanic ventilation in 19%. After 30 days of follow-up, 17 deaths were observed (21%) and 14 attributed to PCP: mortality was worse in AP+ (31%) than in AP- (19%). The main conclusions of our study are the followings: HIV related PCP is still in 1995 frequent and severe; atypical features should not rule out diagnosis; preventive measures are neither sufficient nor efficient. PCP remains in 1995 a priority in HIV related public health and therapeutical research.

Topics: Adult; Aerosols; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Female; Humans; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Recurrence; Retrospective Studies; Serum Albumin; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the safety of dapsone prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients with prior intolerance to trimethoprim/sulfamethoxazole (TMP/SMX).. We conducted a retrospective study in the categorical human immunodeficiency virus out-patient program of a university hospital. Patients who had filled prescriptions for dapsone at our pharmacy between January 1991 and April 1994 were evaluated and 75 patients were found eligible for analysis.. The overall incidence of adverse events (AE) in our study cohort was 39%. The most common AEs were anemia (23%) and rash (16%). However, after critical evaluation of each case, only 3 cases of anemia (4%) and 2 cases of rash (3%) were judged to be "likely related" to dapsone. Only 5/75 patients (7%) developed the same intolerance to dapsone as previously experienced on TMP/SMX, and none of these cases was viewed as "likely related" to dapsone. A dapsone regimen of 100 mg qd and a prior episode of PCP were associated with a higher incidence of AEs. Eight cases of PCP occurred in spite of dapsone prophylaxis for an incidence of 7 cases per 1,000 patient-months. Seven of the cases of PCP occurred in patients who were receiving secondary prophylaxis.. Given the low incidence of AEs judged to be "likely related" to dapsone, this drug is a reasonable choice for PCP prophylaxis in patients with prior AEs to TMP/SMX.

Topics: Adult; Anti-Infective Agents; Anti-Infective Agents, Urinary; Dapsone; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Drug therapies for patients with human immunodeficiency virus (HIV) infection are associated with adverse events that can potentially limit their effectiveness. We sought to quantify the incidence of these events in clinical practice and determine whether there were demographic and clinical differences in adverse event rates for these drugs.. We calculated specific and overall adverse event rates from use of zidovudine, didanosine, zalcitabine, cotrimoxazole, and dapsone in an observational urban cohort of 1,450 HIV-infected patients with a CD4+ count of 500 cells/mm3 or less. We compared adverse event rates by gender, race, age, injecting drug use, and CD4+ count.. Overall adverse event rates in order of incidence were dapsone, 16.2 per 100 person-years (PY); didanosine, 24.1 per 100 PY; zidovudine, 26.3 per 100 PY; cotrimoxazole, 26.3 per 100 PY; and zalcitabine, 37.0 per 100 PY. Rates increased significantly with decline in CD4+ count from > 200 to < 100 cells/mm3 for all drugs but dapsone. In addition, women were more likely than men to have an adverse event for didanosine (relative risk [RR] = 2.7, P = 0.03) and from cotrimoxazole (RR 1.5; P = 0.05). Whites were at greater risk than blacks for adverse events from cotrimoxazole (RR = 1.6, P = 0.03). Only 22 of 357 total events (6%) required hospitalization, and there were no deaths.. Adverse events from antiretroviral drugs and Pneumocystis carinii pneumonia prophylaxis that interrupt therapy are relatively common, although serious events requiring hospitalization are rare. Adverse event rates increase progressively with decline in CD4+ count. The gender and race of the patient modify the risk of adverse events for some drugs.

Topics: Adult; Antiviral Agents; CD4 Lymphocyte Count; Dapsone; Didanosine; Female; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Urban Health; Zalcitabine; Zidovudine

Meningitis is a frequent complication of the human immunodeficiency infection. Possible causes include bacterial, fungal, mycobacterial, syphilitic, and vital pathogens (including the human immunodeficiency virus). Drugs must also be considered in the differential diagnosis. Two patients with probable trimethoprim-sulfamethoxazole-induced meningitis are described in the setting of human immunodeficiency virus infection.

Topics: Adult; Anti-Infective Agents; HIV Infections; Humans; Male; Meningitis, Aseptic; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Although Pneumocystis carinii pneumonia (PCP) is known to occur in adults with systemic lupus erythematosus (SLE), this infection has rarely been described in childhood SLE. We describe 3 children with SLE who developed PCP and describe risk factors for this complication.. A retrospective case review.. All 3 children had severe active SLE with organ involvement requiring immunosuppressive therapy, but the clinical presentations of PCP differed in each patient. They shared some of the known risk factors for opportunistic infection in adults with SLE, including lymphopenia, but severe lymphopenia (< 0.35 x 10(9)/1) was not seen.. PCP is an uncommon but serious complication of childhood SLE, and should be considered in the presence of respiratory symptoms, however subtle. The role of oral chemoprophylaxis is discussed.

Topics: Adolescent; Anti-Bacterial Agents; Child; Fatal Outcome; Female; Humans; Immunosuppressive Agents; Lung; Lupus Erythematosus, Systemic; Pneumocystis; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non-lymphoblastic leukaemia (ANLL) patients, 16 acute lymphoblastic leukaemia (ALL) patients] received TD and 31 patients (8 ANLL patients, 23 ALL patients) received SD from 1987 until 1991. TD consisted of colistin sulphate, neomycin, cephaloridine and amphotericin B orally as well as Orabase and sterilized food, while the patients were nursed in a single room. SD consisted of oral colistin sulphate, neomycin and amphotericin B. Those patients with ANLL were nursed in a single room; patients with ALL were nursed in a single room during remission induction therapy only. All patients except those with ANLL receiving TD received Pneumocystis carinii pneumonia prophylaxis with cotrimoxazole. Because the two groups were heterogeneous for diagnosis and chemotherapy the occurrence of fever (central body temperature at least 38.5 degrees C) and major infections (septicaemia of infections of the deep tissues or organs) were registered during periods of neutropenia (neutrophilic granulocytes < or = 500/mm3 for at least 8 days). Patients on TD had 55 periods of neutropenia, patients on SD 80. Patients on TD had 89.1 periods of fever/100 periods of neutropenia whereas patients on SD had 56.3. Also patients on TD had 27.3 major infections/100 periods of neutropenia whereas patients on SD had 11.3. Major infections predominantly consisted of septicaemia caused by gram-positive bacteria. We conclude that, in this study, TD in a non-protective environment does not offer better protection against major infections that SD in patients with ALL or ANLL.

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Carboxymethylcellulose Sodium; Cephaloridine; Cephalosporins; Child; Child, Preschool; Colistin; Drug Therapy, Combination; Food Handling; Gram-Negative Bacterial Infections; Humans; Infant; Intestines; Leukemia, Myeloid, Acute; Neomycin; Neutropenia; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Sterilization; Trimethoprim, Sulfamethoxazole Drug Combination

The anti-Pneumocystis carinii response of terbinafine together with that of three other compounds, trimethoprim sulphamethoxazole (TMP-SMX), atovaquone (ATQ) and albendazole (ALB), has been investigated in immunosuppressed Sprague-Dawley rats with established pneumocystosis. Drugs were administered orally (terbinafine in dosages of 40 and 80 mg/kg per day, TMP 12.5 mg/kg per day plus SMX 62.5 mg/kg per day, ATQ 100 mg/kg per day and ALB 600 mg/kg per day) to six rat groups except one which served as a control. P. carinii pneumonia (PCP) was identified post-mortem in nine (90%) of the control rats which exhibited a marked P. carinii burden, and mean lung weights were higher with respect to the other treatment groups. During treatment, five rats in the control group died, whereas between 11 and 13 rats in all treatment groups survived. In the terbinafine groups (40 mg and 80 mg/kg per day), a mild P. carinii infection developed in three and two rats (27.2 and 18%), respectively, and almost the same infectivity score was obtained for those treated with 40 mg and 80 mg/kg per day. Histological changes in the lungs in animals receiving terbinafine treatment were minimal. Among the remaining compounds the rate of infection was seven (58.3%) for the ALB treatment group and five (45.4%) for the ATQ group (mean score 19.4 +/- 7.1 and 23 +/- 2.1, respectively). In the TMP-SMX treatment group, there were 13 surviving rats and P. carinii organisms were found in two (15.3%, mean infection score 8 +/- 1.1).

Topics: Administration, Oral; Albendazole; Animals; Antifungal Agents; Atovaquone; Drug Administration Schedule; Immunosuppression Therapy; Lung; Naphthalenes; Naphthoquinones; Pneumonia, Pneumocystis; Rats; Rats, Sprague-Dawley; Terbinafine; Trimethoprim, Sulfamethoxazole Drug Combination

Severe cellular immunosuppression developed in a 25-year-old man with hemophilia B who was infected with the human immunodeficiency virus (HIV). Four days after administration of sulfamethoxazole-trimethoprim (SMX-TMP) for prophylaxis against Pneumocystis carinii pneumonia (PCP), diffuse uptake of both lungs was confirmed on a 67Ga scintigram. Reticular shadows were also seen throughout both lung fields on a chest CT scan. These findings were compatible with PCP, according to the guidelines for presumptive diagnosis of the acquired immunodeficiency syndrome, published by the Centers for Disease Control and Prevention. The dose of SMX-TMP was increased, but interstitial pneumonitis worsened and was accompanied by fever, skin rash, and liver dysfunction, which are common in HIV-infected patients receiving SMX-TMP. No evidence of PCP or of any other opportunistic infection was found by bronchoalveolar lavage. Adverse reactions diminished after SMX-TMP administration was stopped. The 67Ga scintigram and chest CT findings also returned to normal. We concluded that the interstitial pneumonitis was induced by SMX-TMP. SMX-TMP is the first choice anti-PCP drug, but a high incidence of adverse reactions in patients with HIV infection has been reported. Therefore the possibility of SMX-TMP-related pulmonary toxicity must be considered in HIV-infected patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Diagnosis, Differential; Drug Therapy, Combination; Hemophilia B; Humans; Immunocompromised Host; Lung Diseases, Interstitial; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Desensitization, Immunologic; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Hypouricemia has been reported in a substantial fraction of patients with AIDS and attributed to an HIV-related renal urate transport defect. We tested the alternative hypothesis that hypouricemia was associated with the administration of high-dose trimethoprim-sulfamethoxazole (TMP-SMX).. Sociodemographic, clinical, and repeated laboratory data on 45 hospitalized patients with Pneumocystis carinii pneumonia (PCP) with and without HIV infection, were abstracted by a blinded reviewer. The primary outcome of interest was the percent change in serum uric acid concentration from baseline to hospital day 5 +/- 1.. Subjects who received TMP-SMX were older (mean age 44.8 vs. 37.0, p = 0.02), less likely to be HIV-seropositive (61% vs. 94%, p = 0.01), and more likely to have received glucocorticoid therapy (75% vs. 35%, p = 0.01) than those who received pentamidine, dapsone-trimethoprim, clindamycin-primaquine, sulfadiazine-pyramethamine, or a combination of these agents. The administration of TMP-SMX was associated with a 37% +/- 12% reduction in serum uric acid concentration, adjusting for the effects of age, sex, race, HIV antibody status, renal function, serum sodium, and the use of diuretics and glucocorticoids (p = 0.005).. Among a diverse cohort of hospitalized patients with PCP, treatment with high-dose TMP-SMX was strongly associated with a reduction in serum uric acid concentration over time.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Case-Control Studies; Cohort Studies; Female; Hodgkin Disease; Humans; Male; Pneumonia, Pneumocystis; Risk Factors; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Uric Acid

Topics: Acquired Immunodeficiency Syndrome; Erythema; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line drug for prophylaxis and treatment of Pneumocystis carinii pneumonia (PCP) and for prophylaxis of toxoplasmosis in HIV-infected patients. Evidence indicating intolerance related to the dose of SMX led us to examine the efficacy of altered TMP-SMX ratios in a corticosteroid-treated rat model. Infections were assessed by counting P. carinii cysts in lung and by titration of Toxoplasma gondii burdens in tissue culture. For prophylaxis, the reference regimen of 20 mg/kg TMP plus 100 mg/kg SMX was effective. Reduced doses of SMX (5 and 20 mg/kg) effective against PCP were effective against toxoplasmosis, provided the TMP dose was increased to 100 mg/kg. For curative treatment, the reversed ratio of 100 mg/kg TMP plus 20 mg/kg SMX was not effective. These results may provide a basis for altering the TMP-SMX ratios in setting of prophylaxis for both infections, especially in HIV infected patients who often poorly tolerate sulfonamides.

Topics: Animals; Anti-Infective Agents; Cells, Cultured; Dose-Response Relationship, Drug; Fluorescent Antibody Technique, Indirect; HIV Infections; Lung; Male; Pneumocystis; Pneumonia, Pneumocystis; Rats; Rats, Wistar; Toxoplasma; Toxoplasmosis, Animal; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the incidence of and risk factors for toxoplasmic encephalitis among HIV-infected persons.. Medical facility-based prospective medical record reviews of consecutive patients.. We analysed data collected from January 1990 through August 1995 in more than 90 inpatient and outpatient medical facilities in nine US cities. Incidence was calculated as cases per 100 person-years and risk ratios (RR) for annual incidence were calculated using proportional hazards regression while controlling for city, sex, race, age, county of birth, HIV exposure mode, and prior prescription of trimethoprim-sulfamethoxazole (TMP-SMX).. The incidence of TE was 4.0 cases per 100 person-years among persons with a CD4+ T-lymphocyte count of < 100 x 10(6)/l. In multivariate analysis, among the nine cities the annual incidence of toxoplasmosis was significantly lower only in Denver [RR, 0.3; 95% confidence interval (CI), 0.1-0.7; referent city, Seattle]. Persons prescribed TMP-SMX were half as likely to develop toxoplasmic encephalitis as those who were not (RR, 0.5; 95% CI, 0.4-0.7). Of the 4173 persons with AIDS (1987 Centers for Disease Control and Prevention definition) who died during the study period, 267 (6.4%) had toxoplasmic encephalitis in the course of HIV disease.. Toxoplasmic encephalitis in HIV-infected persons varies by geographic area in the United States. TMP-SMX reduces the risk for toxoplasmic encephalitis.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Female; HIV-1; Humans; Male; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

The records of 206 patients with advanced infection due to human immunodeficiency virus type 1 who were receiving prophylaxis with clindamycin/primaquine (C/P), trimethoprim-sulfamethoxazole (TMP-SMZ), or dapsone to prevent Pneumocystis carinii pneumonia (PCP) were retrospectively examined. Two hundred sixty-two patient-years of prophylaxis were accrued (176.2 of TMP-SMZ, 63.4 of dapsone, and 22.8 of C/P). The rates of PCP in the TMP-SMZ, dapsone, and C/P groups were 3.4, 11.0, and 30.7 per 100 patient-years, respectively. Pairwise comparisons showed C/P to be less effective than TMP-SMZ (relative risk [RR], 9.02; 95% confidence interval [CI], 3.03-26.83). A similar trend was apparent for C/P vs. dapsone (RR, 2.78; 95% CI, 0.98-7.93). When only those receiving primary prophylaxis were analyzed, C/P recipients remained at greater risk than TMP-SMZ recipients (RR, 13.19; 95% CI, 3.54-49.12) and dapsone recipients (RR, 3.85; 95% CI, 1.12-13.31). Failure of C/P prophylaxis could be due, at least in part, to underdosing (clindamycin, 300 mg/d; primaquine, 15 mg/d). C/P recipients had more nonspecific diarrhea than did TMP-SMZ recipients (RR, 2.99; 95% CI, 1.61-5.55).

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; CD4 Lymphocyte Count; Clindamycin; Dapsone; Diarrhea; Drug Hypersensitivity; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Hematologic Diseases; HIV Infections; HIV-1; Humans; Male; Pneumonia, Pneumocystis; Primaquine; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The prognosis of first episodes of HIV-associated PCP has markedly improved. The knowledge about the reasons for this progress could bear important implications for the management of HIV-infected patients.. Clinical and laboratory parameters, as well as therapy and clinical course were documented. Prognostic analysis was performed using a logistic regression model. Early (1985-1988) and late (1989-1994) episodes were compared with regard to the results of the prognostic analysis.. 67 patients (61 male, six female, mean age 35 +/- 12 years) without any prophylaxis presenting with a first episode of PCP were treated from 1985 until 1994. 95% of patients had a known HIV-serostatus prior to the diagnosis of PCP. Hemoglobin, percentage of neutrophils in BALF as well as AaDO2 were variables significantly associated with lethal outcome. The prognosis of late episodes was significantly improved (7 versus 32% lethal outcomes, log rank p < 0.01). AaDO2 as the only parameter found to be significantly associated with outcome was significantly lower in the late episodes, accordingly. The mean time until diagnosis of PCP was five days shorter in this group. Moreover, CD8 cell-count and serum albumin were found to be significantly higher, and mean loss of weight prior to diagnosis of PCP significantly lower.. The prognosis of first episodes of PCP without any prophylaxis is most closely associated to the severity of pneumonia as reflected by AaDO2. Causes for a minor severity of PCP include an earlier diagnosis as well as better immunity and a better clinical performance at the time of PCP. The improved prognosis therefore results from the experience of the treatment center. A known HIV-serostatus and regular medical care by an experienced treatment center contributes significantly to improved outcome of PCP also in the group non-compliant to distinctive recommendations with regard to prophylaxis for PCP.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Cause of Death; Eflornithine; Female; Humans; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Respiratory Function Tests; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Insufficiency; AIDS-Related Opportunistic Infections; Anti-Infective Agents; HIV Seropositivity; Humans; Hyperkalemia; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To study the outcome of a modified oral desensitization protocol for trimethoprim-sulfamethoxazole in human immunodeficiency virus infected patients with Pneumocystis carinii pneumonia and acquired immune deficiency syndrome.. A prospective study.. Tertiary care referral center.. Thirteen human immunodeficiency virus infected patients with Pneumocystis carinii pneumonia and allergy to sulfonamides who failed alternative therapy.. Oral desensitization to trimethoprim-sulfamethoxazole.. Nature of allergic reactions, toxicity of alternate medications, indication as well as outcome of trimethoprim-sulfamethoxazole desensitization and routine laboratory determinations.. The most common reaction to trimethoprim-sulfamethoxazole was generalized, pruritic maculopapular rash (n = 10, 76.9%) followed by urticaria/angioedema in two patients (15.38%). Two patients had generalized pruritus without rash. All patients (n = 13) tolerated oral desensitization to trimethoprim-sulfamethoxazole without any adverse reactions including three patients who were critically ill and on mechanical ventilation. Thus the success rate of our protocol was 100%. No patient had received antihistamines prior to or during the protocol. Four patients (5, 6, 7, and 9) were receiving prednisone for severe Pneumocystis carinii pneumonia. Total followup has ranged from 4 to 84 weeks. Two patients died during followup due to causes unrelated to desensitization. All other patients are tolerating trimethoprim-sulfamethoxazole without any allergic reactions.. Oral desensitization to trimethoprim-sulfamethoxazole, as per this protocol is safe, in that there were no systemic or cutaneous reactions during desensitization as well as followup. It is well tolerated in all patients, including the three critically ill patients. As judged by the outcome and ability to tolerate trimethoprim-sulfamethoxazole after desensitization, the procedure is successful in all patients in this study. Equipped with this protocol one can evaluate possible mechanisms of desensitization such as oral tolerance or mediator depletion in a controlled fashion.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Anaphylaxis; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Algorithms; Anti-Infective Agents; Antifungal Agents; Dapsone; Female; Home Care Services; Humans; Male; Patient Compliance; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Pneumocystis carinii pneumonia (PCP) is a leading cause of illness and death in AIDS patients, accounting for about one-third of AIDS deaths. It was rare until the 1980s, when only 50 percent of patients with PCP survived an episode of the disease. Increasingly, prophylactic treatment is being used to prevent the onset of the disease. The use of oral antibiotics is discussed, and guidelines for early diagnosis and effective treatment are included.

Topics: AIDS-Related Opportunistic Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To measure the incidence of cutaneous hypersensitivity reactions to cotrimoxazole in the setting of primary Pneumocystis carinii pneumonia (PCP) prophylaxis: to measure the incidence of severe reactions: and to identify predictors for these outcomes.. Retrospective cohort study.. One university-based outpatient HIV clinic and one university-affiliated internal medicine and infectious disease medical practice.. Two hundred thirty-six HIV-infected individuals receiving cotrimoxazole for primary PCP prophylaxis.. None.. Occurrence of a cutaneous hypersensitivity reaction, defined as rash, fever, or pruritus that resulted in permanent discontinuation of cotrimoxazole. Severe reactions were defined as those resulting in hospital admission or systemic treatment with a corticosteroid. Cox regression was used to calculate relative rates (RRs) and 95% confidence intervals (CIs) for a number of clinical and laboratory variables.. Forty-eight (20%) subjects developed cutaneous hypersensitivity reactions, with six (12.5%) of these being severe. In the unadjusted analysis, the following factors demonstrated at least borderline association: male gender [RR (95% CI) = 0.46 (0.21-0.99)], higher CD4 percentage [RR (95% CI) = 0.95 (0.90-1.00)], syphilis history [RR (95% CI) = 0.37 (0.13-1.04)], and higher total protein [RR (95% CI) = 0.70 (0.45-1.09)]. Adjustment for potential confounding by measured variables did not meaningfully change these results.. Cutaneous hypersensitivity reactions to cotrimoxazole in the setting of primary PCP prophylaxis are common. Although male gender, higher CD4 percentage, syphilis history, and higher total protein have at least borderline associations with these reactions, routinely collected clinical and laboratory variables do not appear to be sufficiently associated with the reactions to permit development of a clinically useful prediction rule.

Topics: Adult; Aged; Anti-Infective Agents, Urinary; Antibiotic Prophylaxis; Cohort Studies; Drug Hypersensitivity; Female; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Female; HIV Infections; HIV Seropositivity; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Mass Screening; Pneumonia, Pneumocystis; Pregnancy; Pregnancy Complications, Infectious; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Pneumocystis carinii pneumonia (PCP) is the most common opportunistic infection in children who have acquired immunodeficiency syndrome (AIDS). Despite the publication of guidelines for prophylaxis against PCP for children infected with human immunodeficiency virus (HIV) in 1991 (1), ongoing AIDS surveillance has detected no substantial decrease in PCP incidence among HIV-infected infants. Studies indicate that this continued incidence is associated with failure to identify HIV-infected children before PCP occurs and with limitations in the ability of CD4+ measurements to identify children at risk for PCP. In March 1994, the National Pediatric & Family HIV Resource Center, in collaboration with CDC, convened a working group to review additional data about the occurrence of PCP among HIV-infected children and to reevaluate the 1991 PCP prophylaxis guidelines for children. This report summarizes these new data and presents revised PCP prevention guidelines that recommend a) promptly identifying children born to HIV-infected women and initiating regular diagnostic and immunologic monitoring of such children; b) beginning PCP prophylaxis at 4-6 weeks of age for all children who have been perinatally exposed to HIV; c) continuing prophylaxis through 12 months of age for HIV-infected children; and d) making decisions regarding prophylaxis for HIV-infected children > or = 12 months of age based on CD4+ measurements and whether PCP previously has occurred.

Topics: AIDS Serodiagnosis; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Chemoprevention; Child, Preschool; Female; HIV Infections; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acidosis, Renal Tubular; Adult; AIDS-Related Opportunistic Infections; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Current dosage regimens of trimethoprim-sulfamethoxazole used to treat Pneumocystis carinii pneumonia in AIDS patients have been based on data from healthy subjects or patients without AIDS. The clearance and absorption characteristics of the drugs may potentially be different between patients with and without AIDS. This study was conducted to assess the pharmacokinetics of trimethoprim-sulfamethoxazole in critically ill and non-critically ill AIDS patients treated for P. carinii pneumonia. Patients received trimethoprim at 15 mg/kg of body weight and sulfamethoxazole at 75 mg/kg of body weight daily intravenously in three to four divided doses and were switched to the oral route when the regimen was tolerated. Serum samples for determination of drug concentrations were obtained over 12 h after intravenous and oral dosing. The pharmacokinetics of trimethoprim and sulfamethoxazole were compared in eight critically ill versus nine non-critically ill male patients and were as follows, respectively: clearance, 1.88 +/- 0.44 versus 1.73 +/- 0.64 ml/min/kg for trimethoprim and 0.40 +/- 0.12 versus 0.34 +/- 0.11 ml/min/kg for sulfamethoxazole; volume of distribution, 1.6 +/- 0.5 versus 1.5 +/- 0.5 liters/kg for trimethoprim and 0.5 +/- 0.3 versus 0.4 +/- 0.1 liters/kg for sulfamethoxazole; and half-life, 10.9 +/- 7.4 versus 11.3 +/- 4.0 h for trimethoprim, and 15.5 +/- 9.5 versus 14.3 +/- 4.7 h for sulfamethoxazole. No significant differences (P > 0.05) were observed between patient groups, although there was wide intersubject variability. Absorption appeared to be similar between the critically ill and non-critically patients: bioavailability was 97.5% +/- 22.4% versus 101.8% +/- 22.7% for trimethoprim and 86.2% +/- 17.9% versus 99.1% +/- 20.5% for sulfamethoxazole, respectively. Because of the similar pharmacokinetics of trimethoprim-sulfamethoxazole in critically ill and non-critically ill AIDS patients, the two groups of patients may receive similar dosages. Dosage adjustment does not appear to be required when switching from the intravenous to the oral route.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; APACHE; Biological Availability; Critical Illness; Half-Life; Humans; Injections, Intravenous; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the prevalence, presentation, and risk factors of pentamidine-induced dysglycemia.. Blood glucose values were screened in 244 consecutive immunocompromised patients with Pneumocystis carinii pneumonia: 116 being treated with cotrimoxazole and 128 others with pentamidine.. Two cotrimoxazole patients developed diabetes as a result of necrotizing pancreatitis (1.7%); the others remained euglycemic. Forty-eight pentamidine-treated patients (38.5%) developed severe glucose homeostasis disorders: hypoglycemia in 7, hypoglycemia and then diabetes in 18, and diabetes alone in 23 (P < 0.001 vs. the cotrimoxazole group). Hypoglycemia was early, sudden, often recurrent, and life-threatening, associated with inappropriately high insulin levels in plasma; the B-cell response to stimuli was poor. Of the 41 diabetic patients, 26 required insulin therapy; their plasma C-peptide levels were lower than normal, and the B-cell secretory responses to stimuli were poor. Islet cell antibodies, insulin antibodies, and insulitis were not detected. The pentamidine-treated dysglycemic patients differed from their euglycemic counterparts by higher pentamidine doses (P < 0.001), higher plasma creatinine levels (P < 0.001), and more severe anoxia (P < 0.05) and shock (P < 0.001). Most of them had received pentamidine mesylate parenterally (n = 36; 75%); six others received the isethionate salt and six exclusively pentamidine aerosols.. Pentamidine-induced dysglycemic accidents are primarily due to inappropriate insulin release and toxicity to the islet B-cells. Drug accumulation due to excessive doses, iterative courses, and/or renal impairment is the determining risk factor.

Topics: Adult; AIDS-Related Opportunistic Infections; Diabetes Mellitus; Female; Humans; Hyperglycemia; Hypoglycemia; Infusions, Intravenous; Male; Pentamidine; Pneumonia, Pneumocystis; Radioimmunoassay; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

To identify clinical and epidemiological factors associated with failure of Pneumocystis carinii pneumonia (PCP) prophylaxis in those receiving primary and secondary prophylaxis.. Longitudinal cohort study of participants infected with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study who used PCP prophylaxis regimens after their T-helper lymphocyte counts had decreased to less than 0.200 x 10(9)/L (200/microL).. Occurrence or recurrence of PCP.. A total of 476 participants reported taking one or more of the following regimens: trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, and/or aerosolized pentamidine--367 as primary prophylaxis and 109 as secondary prophylaxis after a previous episode of PCP. A total of 92 (20%) developed PCP despite prophylaxis. The mean failure rates per person-year of follow-up were 16.0% for those receiving primary prophylaxis and 12.1% for those receiving secondary prophylaxis (P = .19). Median times to death after initiation of primary or secondary prophylaxis were 2.0 and 1.2 years, respectively. The main predictor for failure of PCP prophylaxis was profound T-helper lymphocytopenia; 86% of failures occurred after T-helper cell counts decreased to less than 0.075 x 10(9)/L and 76% occurred after counts decreased to less than 0.050 x 10(9)/L. In multivariate time-dependent analysis, when compared with counts between 0.100 x 10(9)/L and 0.200 x 10(9)/L, the risk ratio for failure with counts less than 0.050 x 10(9)/L was 2.90 (P < .001). Once T-helper cell counts were considered, fever was the only other health status indicator that predicted subsequent PCP (ie, a time-dependent risk ratio of 2.22; P = .01). Use of TMP-SMX as the prophylaxis regimen was protective but did not eliminate failure (ie, a time-dependent risk ratio of 0.55; P = .03).. These findings strongly support identifying improved methods of PCP prophylaxis once T-helper cell counts decrease to less than 0.075 x 10(9)/L or 0.100 x 10(9)/L. Given this severe degree of immunosuppression, an inherently more effective regimen against P carinii is required.

Topics: Adult; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Dapsone; HIV Infections; HIV-1; Humans; Immune Tolerance; Longitudinal Studies; Male; Multivariate Analysis; Pentamidine; Pneumonia, Pneumocystis; Proportional Hazards Models; Recurrence; Survival Analysis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aerosols; AIDS-Related Opportunistic Infections; Clinical Trials as Topic; Humans; Pentamidine; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

An antimicrobial agent trimethoprim-sulfamethoxazole (Tmp-Smx) does not usually cause electrolyte disturbances at regular doses, and few cases of Tmp-Smx-induced electrolyte imbalance have been reported in the English-language literature to date. Recently, however, we treated two patients with Pneumocystis carinii pneumonia who developed severe hyponatremia and hyperkalemia on administration of high-dose Tmp-Smx. These electrolyte disturbances were attributable to the direct effect of Tmp-Smx on the renal distal tubules, were reversible, and corrected by infusion of a sodium-enriched and potassium-free liquid. Therefore, it is suggested that even after electrolyte disturbances have occurred, high-dose Tmp-Smx therapy may be continued for severe infectious diseases under appropriate electrolyte correction.

Topics: Humans; Hyperkalemia; Hyponatremia; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the incidence of symptomatic urinary tract infections in HIV seropositive patients and to assess whether this varies with stage of disease, risk group or the use of co-trimoxazole as prophylaxis against Pneumocystis carinii pneumonia.. A retrospective case note review of 175 HIV-infected patients attending The Royal London Hospital between July 1988 and December 1992 was performed. A urinary tract infection was defined as a pure culture of > or = 10(5) colony forming units in a mid-stream specimen of urine from a patient with symptoms consistent with a urinary tract infection.. Urinary tract infections occurred in 10 (5.7%) of 175 patients, with an incidence of 1.49 per hundred patient years. Urinary tract infections were significantly more common in patients with AIDS or a CD4 lymphocyte count below 0.2 x 10(9)/l (or both) when compared to those without AIDS and a CD4 lymphocyte count above 0.2 x 10(9)/l (5.4 vs. 0.5 urinary tract infections per hundred patient years, p = 0.00005). Women with AIDS or a CD4 count below 0.2 x 10(9)/l (or both) had an incidence of urinary tract infection of 18.5 per hundred patient years. No significant difference was found between the incidence of urinary tract infections in those taking co-trimoxazole as Pneumocystis carinii pneumonia prophylaxis and those taking alternative or no prophylaxis (2.6 vs 6.4 per hundred patient years, p = 0.39).. Urinary tract infection represents a considerable health problem amongst HIV infected patients. Our data show that urinary tract infections are more common in patients with advanced compared with early HIV infection. Cotrimoxazole, when taken by patients as prophylaxis against Pneumocystis carinii pneumonia did not appear to reduce the incidence of urinary tract infection.

Topics: CD4 Lymphocyte Count; Female; HIV Seropositivity; Homosexuality; Humans; Incidence; Male; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Sex Factors; Substance-Related Disorders; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Adult; Female; Humans; Kidney; Lupus Erythematosus, Systemic; Lupus Nephritis; Pneumonia, Pneumocystis; Remission Induction; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; AIDS-Related Opportunistic Infections; Fatal Outcome; Humans; Hyperkalemia; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Animals; Cohort Studies; Feces; Humans; Microsporida; Microsporidiosis; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The prophylactic efficacies of atovaquone (ATQ) alone and in combination with azithromycin, clarithromycin, rifabutin, proguanil, PS-15, trimethoprim, co-trimoxazole, or dapsone were investigated in a SCID mouse model of Pneumocystis carinii pneumonia (PCP). ATQ alone was shown to have a significant dose-related effect, and at 200 mg/kg of body weight per day administered orally, the efficacy of ATQ was comparable to that of Septrin (co-trimoxazole). Of the drugs investigated orally in combination with ATQ, only dapsone (25 mg/kg/day) and to a lesser extent PS-15 (5 mg/kg/day) had any noteworthy antipneumocystis activity (at the doses examined) when administered alone. ATQ drug combinations affected the prophylactic efficacy of a subcurative dosage of ATQ (50 mg/kg/day given orally) in the following ways: dapsone (25 mg/kg/day) or co-trimoxazole (25 mg of sulfamethoxazole plus 5 mg of trimethoprim per kg/day) had no significant effect on ATQ, azithromycin (200 mg/kg/day) or clarithromycin (200 mg/kg/day) had a slight additive effect with ATQ, trimethoprim (100 mg/kg/day) or PS-15 (5 mg/kg/day) had an additive effect with ATQ, and proguanil (25 mg/kg/day) or rifabutin (200 mg/kg/day) had a marked synergistic effect on ATQ. The last result was particularly noteworthy as neither proguanil nor rifabutin was effective against PCP when administered alone. None of the drugs examined antagonized the prophylactic activity of ATQ in experimental PCP in SCID mice. The results suggest that clinical trials of ATQ with synergistic drug combinations may now be justified, particularly if such drug combinations improve ATQ's efficacy and broaden its spectrum of activity.

Topics: Animals; Antifungal Agents; Atovaquone; Dapsone; Drug Therapy, Combination; Mice; Mice, SCID; Naphthoquinones; Pneumonia, Pneumocystis; Proguanil; Rifabutin; Trimethoprim, Sulfamethoxazole Drug Combination

Benanomicin A (BNM-A) has antimycotic activities via binding to mannan in the cell walls of fungi. Anti-Pneumocystis carinii activity of the agent was examined in the P. carinii-infected BALB/c nu/nu female mouse model because P. carinii also possesses mannan in the membranes. The infected mice were treated with intraperitoneal injections of six doses of BNM-A (1, 2.5, 5, 10, 30, and 100 mg/kg of body weight), 4 mg of pentamidine isethionate per kg, 100 mg of sulfamethoxazole per kg combined with 20 mg of trimethoprim per kg (co-trimoxazole), or saline for 21 days. Each dosage group consisted of 10 mice. During treatment, five mice in the control group (saline) died, whereas 8 to 10 mice in all treatment groups survived. Almost the same efficacies were obtained for the groups treated with 5 mg or more and 10 mg or more of BNM-A per kg regarding the weight and number, respectively, of cysts found in the lungs as were obtained for the groups treated with pentamidine isethionate and co-trimoxazole. Overall, a dose of 10 mg of BNM-A per kg was effective against P. carinii pneumonia infection in the mice. Thus, BNM-A is a good candidate for a novel treatment for P. carinii pneumonia as a compound with a new mechanism of action against P. carinii.

Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Antifungal Agents; Body Weight; Female; Lung; Mice; Mice, Inbred BALB C; Mice, Nude; Organ Size; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMZ) is the drug of choice as prophylaxis for Pneumocystis carinii pneumonia in patients with AIDS. However, adverse reactions ascribed to TMP-SMZ are common in such patients. We previously described a rapid method of oral TMP-SMZ desensitization in patients with AIDS and varying degrees of intolerance to the drug. To assess the feasibility, safety, and long-term clinical utility of our desensitization protocol, we retrospectively studied 22 consecutive patients who underwent desensitization. Prior to the procedure each of the study subjects had exhibited moderate to severe reactions to TMP-SMZ. Desensitization was successfully completed in 19 (86%) of the patients. The three patients for whom desensitization failed experienced chills and/or vomiting that resolved promptly with symptomatic therapy. One of the 19 patients was unavailable for long-term follow-up. Of the remaining 18 patients, three discontinued taking TMP-SMZ within 2 weeks of desensitization because of macular rash and fever. The other 15 (71%) of the evaluable patients tolerated both desensitization and subsequent prophylaxis and took TMP-SMZ for a mean of 14 months (in some cases, for as long as 41 months). None had P. carinii pneumonia while receiving TMP-SMZ. These results indicate that most patients who are presumed to be TMP-SMZ-intolerant can be rapidly desensitized with oral TMP-SMZ and subsequently receive the drug for protracted periods as effective prophylaxis for P. carinii pneumonia.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Anaphylaxis; Desensitization, Immunologic; Female; Follow-Up Studies; Humans; Male; Pneumonia, Pneumocystis; Retrospective Studies; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; HIV Seropositivity; Humans; Male; Pneumonia, Pneumocystis; Substance Abuse, Intravenous; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Clotrimazole; Dapsone; Fluconazole; Humans; Mycoses; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the risk of developing tuberculosis or other AIDS-related diseases (ARD) in HIV-infected patients treated with corticosteroids as adjunctive therapy for Pneumocystis carinii pneumonia (PCP).. Retrospective study.. Infectious Disease Service of a 1000-bed university teaching hospital in Barcelona, Spain.. HIV-infected patients diagnosed with PCP from 1985 to 1992. Patients were classified into two groups: steroid (group A) and non-steroid (group B) adjunctive therapy. Baseline characteristics, antibiotherapy, dose and duration of steroidal treatment were analysed. Endpoints were either the development of tuberculosis or other ARD or death.. From the 129 patients included in this study 72 were in group A and 57 in group B. No differences between groups were observed in baseline characteristics or mean follow-up period (15 versus 14 months, respectively). The mean total dose of steroids was 420 mg (range, 160-1260 mg) methylprednisolone or its equivalent in dexamethasone, with a mean treatment duration of 12 days (range, 4-33 days). No differences were found in the occurrence of tuberculosis or other endpoints in the first 6 months of follow-up. In addition, the cumulative rate of developing tuberculosis was 7% in group A and 12% in group B at 12 months of follow-up, and 13 versus 12% at 24 months (P = 0.622, Mantel-Cox): 4 versus 4% at 12 months and 27 versus 24% at 24 months (P = 0.873) for non-tuberculosis mycobacterial infection, and 40 versus 42% at 12 months, and 88 versus 66% at 24 months (P = 0.330) for non-mycobacterial ARD. The cumulative survival rate was 79 versus 71% and 46 versus 34% at 12 and 24 months, respectively (P = 0.526).. Our data suggest that the use of corticosteroids during PCP in HIV-infected patients at the doses and for the duration used in our patients did not enhance the risk of developing or relapsing tuberculosis or other ARD.

Topics: Adrenal Cortex Hormones; Adult; AIDS-Related Opportunistic Infections; Dexamethasone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Methylprednisolone; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

We report two cases of prolonged fever in deeply immunocompromised patients with AIDS who had been receiving trimethoprim-sulfamethoxazole (TMP-SMZ) as primary prophylaxis for several months. Investigations of the cause of fever yielded normal or negative findings except that the polymerase chain reaction (PCR) for Toxoplasma gondii in the blood was positive in both cases, and PCR of the bronchoalveolar lavage fluid was positive in one case. After a few days of treatment with pyrimethamine plus clindamycin, the two patients became afebrile and the T. gondii PCR became negative. The patients probably had disseminated toxoplasmosis attenuated by TMP-SMZ. PCR examination of blood for evidence of T. gondii genome may be useful in screening for causes of unexplained fever in patients with AIDS, even those who receive prophylaxis with TMP-SMZ.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Antiprotozoal Agents; Fever; HIV-1; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Time Factors; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

The usefulness of scid mice bearing endogenous Pneumocystis carinii infection as a model for experimental chemotherapy was examined using standard compounds known to be effective against P. carinii. Trimethoprim/sulphamethoxazole was able to reduce pulmonary P. carinii cysts in a dose-dependent manner within the dose range studied (10/50 to 100/500 TMP/SMX mg/kg/d, bd, po, 5 days per week for 30 treatments). However, alterations in associated symptoms of infection (reduced body weight, increased lung weight, increased blood leucocytes and erythrocytes), was apparently not linearly dose-dependent. Blood and lung lavage fluid levels of sulphamethoxazole one hour post administration of trimethoprim/sulphamethoxazole was dose-dependent, but not linear with dose, and was apparently correlated to cyst reduction; trimethoprim was below the limit of detection at this time. Treatment of mice with 100/500 mg/kg/day trimethoprim/sulphamethoxazole required 2 weeks (bd for 10 days of treatment) before changes in indices of infection became significant. Pentamidine (20 mg/kg, sc, three times per week for 3 weeks) was nearly as effective as high-dose trimethoprim/sulphamethoxazole in reducing cysts, whereas lower doses were ineffective. Despite being unable to reduce pulmonary P. carinii infection, even low doses of pentamidine (6 or 2 mg/kg, sc, three times per week for 3 weeks) were able to reduce lung weights and blood leucocyte levels. This model of pulmonary P. carinii infections is amenable to chemotherapeutic intervention in an apparently dose-dependent fashion, and can be used to evaluate the capacity of compounds to eradicate P. carinii and resolve signs of infection.

Topics: Animals; Anti-Infective Agents; Antifungal Agents; Blood Cell Count; Body Fluids; Dose-Response Relationship, Drug; Lung; Mice; Mice, SCID; Organ Size; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

During 1991-94 we treated 51 patients with acute myeloid leukaemias and 3 patients with a myelodysplastic syndrome of refractory anaemia with excess of blasts in transformation. The patients received trimethoprim-sulphamethoxazole (TMP-SMX) 1,920 mg daily as a prophylaxis of Pneumocystis carinii infections and selective decontamination of gastrointestinal tract. The majority of patients received TMP-SMX in their first course of chemotherapy with daunorubicin and cytosine arabinoside. Only one of the 18 patients without TMP-SMX prophylaxis during the first course of chemotherapy developed Pneumocystis carinii pneumonia. That pneumonia was successfully treated by intravenous administration of TMP-SMX 1920 mg four times a day. No other Pneumocystis carinii infection was encountered in all other patients during their clinical follow up or in autopsy material of expired patients. TMP-SMX prophylaxis had to be interrupted in 11 patients due to their suspicious allergic skin reactions, however, TMP-SMX was readministered in all without any skin changes attributable to TMP-SMX during next cycles of chemotherapy. TMP-SMX in a given daily dose of 1,920 mg seems to be a successful prophylaxis of Pneumocystis carinii infections in patients with malignant diseases of hematopoiesis.

Topics: Acute Disease; Adult; Anemia, Refractory, with Excess of Blasts; Humans; Immunocompromised Host; Leukemia, Myeloid; Male; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anemia, Megaloblastic; Antifungal Agents; Humans; Leucovorin; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Fatal Outcome; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Humans; Microbial Sensitivity Tests; Naphthalenes; Naphthoquinones; Pneumocystis; Pneumonia, Pneumocystis; Terbinafine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Humans; Lung; Lung Diseases; Male; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Encephalitis; Female; Humans; Male; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Sulfonamides; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; HIV Infections; Humans; Ketoconazole; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Methylprednisolone; Pneumonia, Pneumocystis; Pneumonia, Viral; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

As more drugs are approved for the prevention of opportunistic infections, concerns regarding the benefits and potential risks of these therapies are arising. A synopsis of the data for prophylaxis against opportunistic infections is provided for the following: Pneumocystis carinii pneumonia, fungal infections, Mycobacterium avium complex, cytomegalovirus infections, and toxoplasmosis. General precautions in using preventive medications for people with fewer than 100 CD4 plus cells are highlighted.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Clarithromycin; Clindamycin; Clinical Trials as Topic; Clotrimazole; Cytomegalovirus Infections; Dapsone; Fluconazole; Ganciclovir; Humans; Itraconazole; Leucovorin; Mycobacterium avium-intracellulare Infection; Mycoses; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Valacyclovir; Valine

Pneumocystis carinii pneumonia (PCP) is common in children and adults who are HIV-positive. More than half of the babies who have PCP never received preventive drugs. It is suggested that a greater number of HIV-exposed infants must be identified at an earlier stage, and preventive medication should be prescribed. It is further recommended that HIV testing and monitoring be made more available to infants at risk so that preventive PCP medication can be given at four to six weeks of age, regardless of the CD4 count and HIV test results. The first choice of treatment is Bactrim or Septra. More information can be obtained by calling the Network at (800) 734-7104.

Topics: Antifungal Agents; Atovaquone; Clinical Trials as Topic; Dapsone; HIV Infections; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Dr. Bernard Bihari, an AIDS specialist practicing in New York City, and other members of the Community Programs for Clinical Research on AIDS (CPCRA), have determined that some of the Public Health Services's recommendations for preventing opportunistic infections do not match the standards of care that the CPCRA developed nearly five years ago. The basic treatments provided by Bihari include using 1) TMP-SMZ and fluconazole to prevent, respectively, Pneumocystis carinii pneumonia (PCP) and cryptococcal meningitis in patients with CD4 counts below 200; 2) using high-dose acyclovir to prevent cytomegalovirus disease when the CD4 counts drop below 150; and 3) using clarithromycin and ethambutol to prevent Mycobacterium avium complex when CD4 counts drop below 100. This protocol has kept many patients from developing these opportunistic infections. Bihari notes that while the Centers for Disease Control and Prevention (CDC) recommendations are based on FDA-approved treatments and large clinical trials, private practitioners do not necessarily have to follow them.

Topics: AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Clarithromycin; Cytomegalovirus Infections; Ethambutol; Humans; Meningitis, Cryptococcal; Mycobacterium avium-intracellulare Infection; New York City; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A case history is presented of an HIV-infected female patient with a recurrence of Pneumocystis carinii pneumonia (PCP) and contraindications to use of most drugs for PCP, including pentamidine, trimethoprim-sulfamethoxazole (TMP-SMX), clindamycin, primaquine, and dapsone. Treatment alternatives discussed address risk-benefit analyses of using different drugs. The final treatment decision was to use escalating doses of TMP-SMX, since her previous adverse effects (fever and rash) are not an absolute contraindication to readministration of the drug. Results of this TMP-SMX were good with trivial side effects.

Topics: AIDS-Related Opportunistic Infections; Female; Humans; Pentamidine; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

A recent Spanish study has shown that Bactrim, a treatment for PCP pneumonia, can be taken three times a week instead of once daily. Using Bactrim, also known as Septra, in this manner produces fewer side effects while still remaining effective. The study confirms the results of several previous small studies done in the U.S.

Topics: Humans; Immunocompromised Host; Neutropenia; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The fungus Pneumocystis carinii, which rarely if ever causes illness in otherwise healthy people, can cause potentially fatal pneumonia in patients with defects of cell-mediated immunity resulting, for example, from chemotherapy or immunosuppression after organ transplantation. P. carinii pneumonia also occurs in up to 85% of patients with acquired immunodeficiency syndrome (AIDS), in many of whom it is the first manifestation of the disease. This article discusses the prevention and treatment of P. carinii pneumonia in adults infected with the human immunodeficiency virus (HIV).

Topics: Adult; AIDS-Related Opportunistic Infections; Dapsone; Drug Therapy, Combination; Fees, Pharmaceutical; Humans; Pentamidine; Pneumonia, Pneumocystis; Severity of Illness Index; Trimethoprim, Sulfamethoxazole Drug Combination

The antiprotozoan and antifungal agent, the terbinafine, was investigated for its potential activity against Pneumocystis carinii infection of the A549 cell line culture and on immunosuppressed Sprague Dawley rats in comparison with trimethoprim-sulphamethoxazole and pentamidine isethionate. Terbinafine suppressed P. carinii growth at doses up to 3 g/L within 24 h and it was able to inhibit cyst forms at 60 h post inoculation. With respect to trimethoprim-sulphamethoxazole and pentamidine isethionate P. carinii organisms decreased at the same time interval but cyst form elimination was less apparent than with terbinafine. The results of the in-vitro culture were consistent with the in-vivo observations. Of the 3 groups of rats tested, the occurrence of P. carinii pneumonia was documented in 18 (60%) of the control rats (group 3) which showed a high degree of P. carinii burden and a marked weight loss with respect to the beginning of the experiment. Among terbinafine treated rats (group 1), P. carinii pneumonia was present in one rat (3.3%), while no P. carinii infection occurred in the pentamidine isethionate and in trimethoprim-sulphamethoxazole treatment rat groups (group 2). All the agents investigated showed no particular signs of toxicity. These preliminary results suggest further explorations of the terbinafine in clinical trials for treatment and prophylaxis of P. carinii pneumonia.

Topics: Animals; Antifungal Agents; Male; Naphthalenes; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Rats; Rats, Sprague-Dawley; Terbinafine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Clarithromycin; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Drug Resistance, Microbial; Homosexuality, Male; Humans; Liver Diseases; Male; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Splenic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Child, Preschool; Dapsone; HIV Infections; Humans; Infant; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the pancreatic beta cells function of HIV patients receiving either 300 mg per month of aerosolized pentamidine (n = 12) or oral trimethoprim-sulfamethoxazole (TMP-SMX), twice a day three times per week (TMP: 160 mg, SMX: 800 mg) (n = 10). Intravenous (i.v.) glucose tolerance tests were performed after i.v. injection of 0.5 glucose by kg of body weight in 30 seconds. Plasma insulin levels were assessed at baseline, 1, 2, 3 and 5 min. Moreover, in patients receiving inhaled pentamidine, plasma glucose amylase and insulin levels were measured every 30 min for 2 hours after the end of the aerosol. Plasma pentamidine levels were measured 30 min after the end of the aerosol. Those tests were performed every 2-3 months for one year. In most patients taking aerosol treatment, pentamidine levels were detectable, remaining under levels of 50 ng/ml. Pentamidine plasma levels increased in a time dependent manner. Baseline plasma glucose, amylase and insulin levels were in normal range and remained stable during the therapy. For 7 out of 12 patients, glucose tolerance tests showed an adequate insulin secretion: the addition of the two best insulin levels were higher than 70 IU/ml. When this criteria was not found (n = 5), a glucagon stimulation test allowed to exclude an endocrine pancreatic dysfunction. Due to its apparent short half-life, increased pentamidine levels could be related to an improvement of spray techniques as well as to a cumulative effect. Pancreatic function was preserved in pentamidine-treated patients compared to TMP-SMX-treated patients.

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; HIV Infections; HIV Seropositivity; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the efficacy of primary chemoprophylaxis in preventing Pneumocystis carinii pneumonia (PCP) in infants with perinatal human immunodeficiency virus-1 infection during the first year of life, we conducted a retrospective chart review of infants with human immunodeficiency virus-1 infection born at New York University Medical Center-Bellevue Hospital Center, in New York. Between March 1989 and March 1993, 24 infants received primary chemoprophylaxis with trimethoprim-sulfamethoxazole in the first year of life and 24 infants did not receive primary prophylaxis. The CD4+ T-lymphocyte counts in the two groups did not differ during the first year of life. The median age at the time of initiation of prophylaxis was 3 months, and the average duration of prophylaxis was 5.5 months. Among the infants who had not received prophylaxis, five cases of PCP were diagnosed at a median age of 5 months; in contrast, no cases of PCP were observed in the infants receiving prophylaxis (log-rank test, p = 0.017). The probability of surviving after 1 year of age was 92% for the children who received prophylaxis and 74% for those who did not (log-rank test, p = 0.035). These data indicate that chemoprophylaxis is highly effective in preventing primary PCP and improving survival time in infants with human immunodeficiency virus-1 infection.

Topics: Age Factors; AIDS-Related Opportunistic Infections; CD4-Positive T-Lymphocytes; Cohort Studies; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Infant; Infant, Newborn; Leukocyte Count; Male; Pneumonia, Pneumocystis; Probability; Retrospective Studies; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Female; HIV Infections; HIV Seropositivity; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii organisms have been shown to persist throughout therapy in the majority of patients with Pneumocystis carinii pneumonia (PCP). This study evaluated the relationship between persistence of organisms and recurrence of disease, and the effect of chemoprophylaxis on bronchoalveolar lavage specimens. Seven patients receiving PCP chemoprophylaxis underwent serial bronchoalveolar lavage (BAL) examinations at 1, 4, and 7 mo after recovery from a first episode of PCP. Specimens were examined for persistent organisms with Gomori's methenamine silver stain and immunofluorescent antibody staining. There were no persistent organisms 1 mo after completion of antimicrobial treatment in six of the seven patients. The one patient with persistent organisms demonstrated clearance of organisms by 4 mo and had no recurrence of PCP. One patient had a recurrence of PCP at 4 mo, after a negative 1-mo BAL. We conclude that a positive BAL result by silver stain or immunofluorescent antibody staining more than a month after ending treatment may indicate clinical recurrence of PCP and not just persistence of nonpathologic cysts. These findings suggest that recurrences of PCP are more likely due to new infection than to relapse of prior disease.

Topics: Adult; AIDS-Related Opportunistic Infections; Bronchoalveolar Lavage Fluid; Dapsone; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with the acquired immunodeficiency syndrome are predisposed to cutaneous drug reactions. The reasons are poorly understood and the circumstances in which such patients can be treated through hypersensitivity are a matter of discussion. We assessed the value of clinical and laboratory parameters for predicting trimethoprim-sulfamethoxazole-induced skin reactions and the effects of continued trimethoprim-sulfamethoxazole therapy in such patients. We retrospectively studied all episodes of nonhypoxemic Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome who were treated with trimethoprim-sulfamethoxazole.. No clinical or laboratory parameters were found to be predictive of trimethoprim-sulfamethoxazole-induced cutaneous reactions. Of 38 patients treated with trimethoprim-sulfamethoxazole, 18 (47%) developed cutaneous reactions; these occurred within a median of 11 days (range, 7 to 20 days). Of these 18 patients, 12 (67%) continued to be treated with trimethoprim-sulfamethoxazole through hypersensitivity. Trimethoprim-sulfamethoxazole treatment was continued in 19 (95%) of the 20 patients who did not develop cutaneous reactions (P = .067). The mean duration of trimethoprim-sulfamethoxazole therapy was shorter (18 days) in patients who developed skin reactions than in those who did not (20 days) (P = .016). Noncutaneous side effects accounted for all but one interruption of therapy.. No clinical or laboratory parameters were found to be predictive of cutaneous reactions. By treating through hypersensitivity, 67% of our patients, who otherwise might have had to stop taking trimethoprim-sulfamethoxazole, were able to continue this essential drug therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Drug Eruptions; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (T/S) is an effective and important prophylactic medication for HIV-infected patients that must frequently be discontinued because of allergic reactions.. Our objective was to assess the safety, the frequency of success, and the duration of desensitization to T/S in HIV-infected patients.. We studied oral desensitization with T/S of patients with a history of allergy to the medication and longitudinal follow-up. Twenty-eight men with a history of T/S-induced skin rashes were studied. Mean age was 35 years (range, 26 to 50 years). Mean CD4 count was 89 cells/mm3 (range, 0/mm3 to 210/mm3). Patients were seen every 4 to 6 weeks. Mean follow-up was 19.07 weeks (range 2 to 81 weeks).. After 32 weeks, 23 of 28 (82%) patients were successfully desensitized (four had rashes develop, and one could not continue for personal reasons). Of the 23 patients who were successfully desensitized, six were known to have subsequently discontinued T/S (four had rashes; two discontinued on the advice of their personal primary physicians). Six patients were lost to follow-up. One patient died of pulmonary Kaposi's sarcoma. Ten patients are taking the medication regularly without any problems.. T/S desensitization is a simple, safe and effective means to provide it for most patients with a history of "allergic" rashes.

Topics: Adult; AIDS-Related Opportunistic Infections; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Dapsone is used in prophylaxis for and treatment of Pneumocystis carinii pneumonia. We present a case of Stevens-Johnson syndrome that was likely induced by administration of dapsone. A review of charts at the HIV Treatment Center of Northwestern University (Chicago) revealed that 40.3% of patients treated with trimethoprim-sulfamethoxazole could not tolerate the medication, while 25.2% of those treated with dapsone were intolerant of the drug. We also found a higher rate of adverse reactions to dapsone among patients with prior intolerance to trimethoprim-sulfamethoxazole than among patients without such a history; however, the difference was not significant.

Topics: Acquired Immunodeficiency Syndrome; Adult; Dapsone; Drug Tolerance; Humans; Male; Pneumonia, Pneumocystis; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Child, Preschool; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Infusions, Intravenous; Injections, Intramuscular; Male; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Twelve of 3803 consecutive marrow allograft patients treated at this center over the past 20 years have had a post-transplant tissue diagnosis of toxoplasmosis: 10 at autopsy and 2 by brain biopsy. This infection was identified in none of 509 autologous marrow recipients. Occurrence of toxoplasmosis was 0.31 cases per 100 allogeneic transplants and 1.0 per 100 autopsies. An estimated 15% of allogeneic transplant recipients were seropositive for Toxoplasma gondii and 2% of seropositive patients developed toxoplasmosis. Pre-transplant serology was positive by both dye and agglutination tests in 11 infected patients tested. Sequential IgG, IgM, IgA, IgE antibody titers to T. gondii and the differential agglutination ratio were not helpful in diagnosing toxoplasmosis. Median day of clinical presentation was day 59 post-transplant (35-97 days) and of diagnosis, day 62 after transplant (37-143 days). Eleven patients had graft-versus-host disease (GVHD) of grades II-IV. All 12 patients died. Infection was diagnosed prior to death in only 16% of patients and contributed to death in at least 40%. Histopathology revealed tachyzoites of T. gondii most prevalent in brain (100%), heart (67%) and lungs (33%), and toxoplasma cysts alone in heart (33%) and lungs (22%). Toxoplasma infection was diagnosed in two patients receiving trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia prophylaxis suggesting this was insufficient prophylaxis for toxoplasmosis. Toxoplasmosis appeared to occur by reactivation within the first 6 months after marrow transplant. Infection developed in patients who were seropositive for T. gondii pre-transplant, had received allogeneic marrow and had severe GVHD.

Topics: Adolescent; Adult; Aged; Animals; Antibodies, Protozoan; Autopsy; Bone Marrow Transplantation; Child; Child, Preschool; Female; Graft vs Host Disease; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Child; Humans; Neoplasms; Pentamidine; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia is frequent in patients with cellular immunity impairments, specially those with AIDS. We communicate our experience in 20 patients (15 with AIDS) with Pneumocystis carinii pneumonia confirmed by the finding of trophozoites or cysts. Clinical manifestations were cough in 75% of cases, dyspnea in 70% and fever in 65%. Eighty five percent of cases had diffuse reticular and nodular radiological densities. Nineteen patients had an increased alveolar-arterial O2 gradient. Nineteen patients were treated with trimethropim-sulphamethoxazole (TMP-SMX) and 4 with pentamidine isethionate (1 due to previous allergy and 3 due to poor response to TMP-SMX). Three patients died during the acute episode. Of the survivors, 13 died within 2 to 44 months later (14.5 +/- 12 months). It is concluded that AIDS is the most frequent underlying condition in patients with Pneumocysts carinii pneumonia and that long term survival is low.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Female; Follow-Up Studies; Humans; Immunocompromised Host; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Prospective Studies; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/sulfamethoxazole (TMP/SMX) is the drug of choice for Pneumocystis carinii pneumonia (PCP) prophylaxis in immunocompromised patients. In children with malignancy, TMP/SMX is well tolerated, but adverse reactions that necessitate discontinuation can occur. We evaluated the safety and efficacy of aerosolized pentamidine (AP) as an alternative prophylaxis modality in children with malignancy who are intolerant of or allergic to TMP/SMX.. AP (200 mg/m2 every 4 weeks) was administered to 60 children with malignancy receiving chemotherapy who had experienced severe adverse reactions to TMP/SMX. Seven hundred twenty doses of AP have been administered during a 3 1/2-year period (21,600 patient-days), with 30 patients treated for > or = 12 months (range, 12 to 25).. Adverse reactions occurred during 79 (10%) of the 720 treatments and included bronchospasm in 23, cough in 40, vomiting in 10, and nausea in six. Only two patients had severe bronchospasm. AP was discontinued due to toxicity in three patients (5%). None of the patients (upper 95% confidence limit, 0.049) have developed PCP.. AP appears to be well tolerated and effective in the prevention of PCP in children with malignancy.

Topics: Adolescent; Aerosols; Child; Child, Preschool; Drug Hypersensitivity; Female; Humans; Male; Neoplasms; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

To report a case of probable pentamidine-induced acute pancreatitis.. A patient was hospitalized because of fever, dyspnea, and productive cough. Chest X-ray revealed diffuse alveolar infiltrates, and the examination of bronchoalveolar lavage demonstrated the presence of Pneumocystis carinii. Intravenous cotrimoxazole was administered but the patient's condition did not improve. As secondary leukopenia appeared, the treatment was changed to pentamidine isethionate 4 mg/kg/d i.v. On day 5 of this new therapy, the patient experienced abdominal pain, and both blood and urine amylase concentrations raised to 330 U/L and 3960 U/L, respectively. The patient died 48 hours later, and signs of acute pancreatitis were observed in necropsy.. With reference to a classical method for estimating the probability of adverse drug reactions, a probable relationship between pentamidine therapy and acute pancreatitis was found in this patient. Furthermore, no alternative causes of pancreatitis were present.. It is likely that pentamidine administration in our patient resulted in an acute episode of pancreatitis. Serum and urine amylase concentrations should be monitored in patients receiving this drug.

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Humans; Male; Methylprednisolone; Pancreatitis; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia has been the most common life-threatening opportunistic infection in patients with acquired immunodeficiency syndrome. With a better understanding of the natural history of HIV infection, however, we have come to realize that prophylaxis against P carinii can prevent the majority of such pneumonias. In this article, I focus on the rationale behind such prophylaxis, as well as the choices and dilemmas the clinician faces in deciding on the most appropriate therapy and when it should be instituted.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Clindamycin; Dapsone; Drug Therapy, Combination; Humans; Pneumonia, Pneumocystis; Primaquine; Pyrimethamine; Streptococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

The efficacy of clarithomycin and sulphamethoxazole for treatment of experimental Pneumocystis carinii infection was investigated. Rats were immunosuppressed with dexamethasone and inoculated intratracheally with 5 x 10(6) P. carinii cysts. After 2 weeks, the lung tissues were assayed for P. carinii cyst burden. The combination of clarithromycin and sulphamethoxazole caused a significantly greater reduction in cyst burden than either drug alone. Up to 50% of the rats treated with the combination of clarithromycin and sulphamethoxazole were negative for P. carinii cysts. Equivalent doses of the individual drugs given alone did not produce cures. The combination of clarithromycin and sulphamethoxazole was more than twice as effective as either drug alone. Clarithromycin combined with sulphamethoxazole in treatment of P. carinii infection could be especially useful since clarithromycin monotherapy provides safe and effective treatment against many other pathogens, including several that are associated with AIDS.

Topics: Animals; Clarithromycin; Dexamethasone; Drug Therapy, Combination; Humans; Immunosuppression Therapy; Male; Pentamidine; Pneumonia, Pneumocystis; Rats; Rats, Sprague-Dawley; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the circumstances, the clinical features and the outcome of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-free patients with connective tissue diseases (CTD).. Retrospective analysis of all cases referred 10 medical units in the last 10 years.. A total of 34 cases of PCP in patients with CTD were studied (Wegener's granulomatosis, n = 12; systemic lupus erythematosus, n = 6; polyarteritis nodosa, n = 4; poly/dermatomyositis, n = 5; others, n = 7). The majority of patients (25/34 patients; 74%) presented PCP during the first 8 months following the diagnosis of CTD. At the time of diagnosis of PCP, most patients (32/34; 94%) were receiving corticosteroids (mean prednisone equivalent dose: 1.2 mg/kg/day) associated in 24 cases with cytotoxic agents (cyclophosphamide, n = 19; methotrexate, n = 5). Most patients were lymphocytopenic at the onset of PCP: 91% (31/34) of patients had fewer than 1.5 x 10(9)/l circulating lymphocytes and 76% (26/34) had fewer than 0.8 x 10(9)/l. The mean duration of prodromal symptoms was 6 days: this is much shorter than for AIDS associated PCP. Half the patients required intensive care for respiratory failure. Mortality was high (11/34 patients; 32%) although deaths were partly due to infections acquired in intensive care units. Among the 23 survivors, 10 (43%) received secondary prophylaxis for PCP and 13 (57%), received the usual therapeutic regimen. No relapse has been observed in either group with a mean followup of 22 months.. Although rare, PCP must be considered in patients with any type of CTD and receiving cytotoxic agents and corticosteroids, particularly if they are lymphocytopenic. Thus, bronchoalveolar lavage must be rapidly performed in patients with CTD presenting with fever, pulmonary infiltrates, hypoxemia and lymphopenia.

Topics: Adult; Aged; Aged, 80 and over; Connective Tissue Diseases; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Prednisone; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Clostridioides difficile; Enterocolitis, Pseudomembranous; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Humans; Male; Mycobacterium avium-intracellulare Infection; Nursing Assessment; Pentamidine; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

The incidence of Pneumocystis carinii pneumonia (PCP) has been shown to be high posttransplantation in the absence of prophylaxis. For this reason, lung transplant recipients routinely receive prophylaxis. We report on our results using aerosolized pentamidine prophylaxis in nine patients post-lung transplantation (eight single lung transplants, one double). The patients received monthly treatments of 300 mg of aerosolized pentamidine for a mean of 10.6 months (range, 4 to 21 months). Patients were routinely monitored with serial pulmonary function studies and bronchoscopy as clinically indicated. Two of the patients experienced bronchospasm in response to the therapy. None of the patients experienced any episodes of PCP during the period of inhaled pentamidine prophylaxis. Inhaled pentamidine is a safe and effective form of PCP prophylaxis and may be used instead of sulfamethoxazole-trimethoprim in patients who have a sulfa allergy or other untoward sulfa side effects.

Topics: Administration, Inhalation; Aerosols; Bronchial Spasm; Bronchoscopy; Drug Hypersensitivity; Forced Expiratory Volume; Graft Rejection; Humans; Immunosuppressive Agents; Lung Transplantation; Maximal Midexpiratory Flow Rate; Nebulizers and Vaporizers; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Spirometry; Trimethoprim, Sulfamethoxazole Drug Combination; Vital Capacity

Topics: Acquired Immunodeficiency Syndrome; Adult; Amylases; Female; Humans; Pancreatitis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Among patients infected with human immunodeficiency virus type 1 (HIV-1), early and widespread use of prophylactic regimens against Pneumocystis carinii is changing the pattern of illnesses related to the acquired immunodeficiency syndrome (AIDS).. We conducted a subcohort analysis of 844 men with AIDS (87 percent of whom have since died) from a prospectively followed cohort of 2592 HIV-1-infected homosexual men.. A total of 138 men received prophylaxis before the diagnosis of AIDS, but 39 (28 percent) nevertheless had P. carinii pneumonia at some time. Only four illnesses occurred more frequently in men who received P. carinii prophylaxis before the onset of AIDS: Mycobacterium avium complex disease, which developed in 33.4 percent, as compared with 17.3 percent of the 706 men who did not receive early prophylaxis; wasting syndrome (18.4 percent vs. 6.4 percent); cytomegalovirus disease (44.9 percent vs. 24.8 percent); and esophageal candidiasis (21.3 percent vs. 12.8 percent). Collectively, these four diseases accounted for the initial AIDS-related illness in 42.7 percent of those who received prophylaxis before the onset of AIDS, as compared with 10.7 percent of those who did not. During the three six-month periods before the diagnosis of AIDS (0 to 6, > 6 to 12, and > 12 to 18 months), the geometric mean CD4+ cell counts were 48, 87, and 147 per cubic millimeter, respectively, in men who received prophylaxis against P. carinii, as compared with 118, 211, and 279 per cubic millimeter in those who did not.. M. avium complex disease, esophageal candidiasis, wasting syndrome, and cytomegalovirus disease are more common in HIV-infected patients who have received prophylaxis against P. carinii than in those who have not. Prophylaxis may delay the first AIDS illness for 6 to 12 months.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Candidiasis; CD4-Positive T-Lymphocytes; Cohort Studies; Cytomegalovirus Infections; Dapsone; Esophageal Diseases; HIV-1; Humans; Leukocyte Count; Male; Mycobacterium avium-intracellulare Infection; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: CD4-Positive T-Lymphocytes; HIV Infections; Humans; Leukocyte Count; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A distinct clinical syndrome of cholestasis and hepatitis occurred during early infancy in seven infants with perinatally acquired human immunodeficiency virus 1 infection. In five infants hepatitis was the first manifestation of human immunodeficiency virus 1 infection. The median age of onset of hepatitis was 7 months (range, 5 to 10 months). The mean total bilirubin concentration at presentation was 7.4 mg/dl (range, 3.9 to 11 mg/dl), the mean aspartate aminotransferase was 1512 IU/liter (range, 782 to 2960 IU/liter) and the mean alanine amino-transferase 512 IU/liter (range, 92 to 1247 IU/liter). The absolute CD4 count at the time of onset of hepatitis ranged from 191 to 2298 cells/mm3 (mean, 766 cells/mm3). Six of the seven children died within 12 weeks of onset of hepatitis, three as a result of complications of Pneumocystis carinii pneumonia, and two died of complications secondary to cytomegalovirus. In only one infant was the cause of death the direct consequence of liver failure. The seventh infant died 17 months after the onset of hepatitis of dilated cardiomyopathy. No specific etiologic agent has been identified as the cause of cholestatic hepatitis in these infants. In situ hybridization studies to detect human immunodeficiency virus 1 messenger RNA was negative in the liver tissue obtained at biopsy and autopsy in five of the samples tested.

Topics: Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; CD4-Positive T-Lymphocytes; Cholestasis; Female; Hepatitis; HIV Infections; HIV-1; Humans; Immunoglobulins; Infant; Jaundice; Leukocyte Count; Liver; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

From 1988 to 1991 the long-term efficacy of a combined therapy with a polyvalent immunoglobulin/cytomegalovirus (CMV) hyperimmunoglobulin, oral low dose zidovudine, oral cotrimoxazole or inhaled pentamidine was investigated in three groups of human immunodeficiency virus (HIV)-infected children. Group 1A consisted of three perinatally infected children with a CD4 cell decrease of > 400 cells/microliters per year. Group 1B were 17 perinatally infected children with a CD4 cell decrease of < 400 cells/microliters per year. Group 2 comprised eight haemophilic children infected by clotting factors. Despite combined therapy none of group 1A survived longer than 12 months showing a rapid loss of CD4 cell counts, progressive encephalopathy, wasting syndrome and severe bacterial, fungal and CMV reactivation. Under pure intravenous immunoglobulin (IVIG) therapy severe bacterial infections were seen in 1 of 12 children in group 1B. The majority of these patients showed increases or stabilisation of length and weight percentiles. In this group low dose zidovudine therapy was of benefit in HIV-associated neurological symptoms. Nevertheless combined therapy could not prevent further deterioration of CD4 cell counts. In group 2 severe bacterial infections were not seen under IVIG therapy. In this group a temporary increase (6 months) of CD4 cell counts under IVIG/zidovudine combined therapy occurred. Pneumocystis carinii pneumonia (PCP) prophylaxis with oral cotrimoxazole or inhaled pentamidine successfully prevented PCP in all three groups. Under CMV hyperimmunoglobulin (n = 22), ten out of ten patients did not acquire primary CMV infection, whereas CMV reactivations mainly located in the CNS could not be prevented in 5 of 12 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: CD4-Positive T-Lymphocytes; Child; Child, Preschool; Cytomegalovirus; Drug Therapy, Combination; HIV Infections; Humans; Immunization, Passive; Immunoglobulins; Immunoglobulins, Intravenous; Infant; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: AIDS-Related Opportunistic Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

In a patient with the acquired immunodeficiency syndrome, a progressive increase in the serum potassium concentration occurred with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) therapy for Pneumocystis carinii pneumonia. In this patient, factors known to alter transcellular potassium shifts to induce hyperkalemia were not present. There was no evidence of glucocorticoid or mineralocorticoid insufficiency at the time of hyperkalemia, while the transtubular potassium gradient decreased. The hyperkalemia resolved spontaneously on discontinuation of TMP-SMX therapy, suggesting that this electrolyte abnormality is related to altered renal tubular secretion of potassium as a consequence of the high-dose TMP-SMX therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Humans; Hyperkalemia; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Hyperkalaemia with renal tubular dysfunction by oral therapy of sulfamethoxazole-trimethoprim (co-trimoxazole) is described in 2 elderly Japanese patients with lymphoid malignancy, who developed Pneumocystis carinii pneumonia and improved. A high dose of cotrimoxazole induced hyperkalaemia with the elevation of serum creatinine and blood urea, and increased urinary N-acetyl glucosaminase after several days of the drug administration in these patients; one patient became unconscious. Discontinuation of co-trimoxazole normalized serum potassium level and symptoms. A repeated low dose of the drug induced hyperkalaemia. Before the treatment of co-trixomazole, their serum levels of creatinine showed upper limits of normal ranges. In the present study, our cases suggested that patients receiving a high dose of co-trimoxazole should be evaluated for these potential complications during a course of treatment, particularly in elderly patients with preexisting renal dysfunction.

Topics: Aged; Humans; Hyperkalemia; Hyponatremia; Kidney Diseases; Kidney Tubules; Leukemia, T-Cell; Lymphoma, Non-Hodgkin; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the efficacy of drugs for treatment, we tried to make an animal model of Pneumocystis carinii (P. carinii) pneumonia. Specific pathogen free (SPF) rats immunosuppressed with corticosteroid were intratracheally inoculated with P. carinii. Six weeks after the inoculation, the lung sections of infected rat lung showed increased numbers of P. carinii in the alveoli and thickening of alveolar septa with mononuclear cell infiltration. From 7 to 9 weeks after inoculation, the intensity of infection became more severe, and some rats died at this period. Then, to evaluate drug efficacy in this model, we finished the drug therapy by the 6th week and used the number of P. carinii in the lung and the inflammation score as an indicator of drug efficacy. In this P. carinii pneumonia animal model, both sulfamethoxazole-trimethoprim clinically established anti P. carinii drug and interferon-gamma which is one of the lymphokines mainly produced by T lymphocytes indicated therapeutic and synergistic efficacy against P. carinii pneumonia.

Topics: Animals; Disease Models, Animal; Drug Synergism; Interferon-gamma; Male; Pneumonia, Pneumocystis; Rats; Rats, Wistar; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of the present was to evaluate the incidence of side effects to Trimethoprim-sulphamethoxazole (TMP-SMX) in 32 patients with AIDS and pneumonia by Pneumocystis carinii.. A retrospective study was carried out following a protocol which included all items related with the drug used.. Side effects to TMP-SMX were seen in 75% of the patients treated with the most important and severe being at a cutaneous level. These severe reactions require withdrawal of the drug and its substitution by pentamidine in half of the cases, while in the remaining 25% the reactions were mild. To date none of the 9 patients prophylactically treated with TMP-SMX have relapsed over 3 years of follow up while 4 out of the 9 treated with pentamidine have had relapsed.. Trimethoprim-sulphamethoxazole is the ideal prophylactic drug for those who are able to tolerate it. Following review of the literature 2 schedules of tolerance induction were proposed for use in patients who have had previous reactions with this drug, including a rapid schedule and another slow schedule.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Drug Administration Schedule; Drug Eruptions; Female; Humans; Incidence; Injections, Intravenous; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Vomiting

At the age of four months, a boy with a normal history and family history, suddenly fell ill with a life-threatening pneumocystis carinii-pneumonia. Surprisingly, this opportunistic infection was not brought about by a T-cell deficiency. However, the patient's diagnosis turned out to be the rare "Hyper-IgM-syndrome", confirmed by: serum levels of IgM always at least normal whereas IgG, IgA and IgE were markedly decreased or absent; the development of neutropenia and occasional diarrhea. Generally, infections with pneumocystis carinii are rare in isolated deficiencies of immunoglobulines, but relatively frequent in primary "Hyper-IgM-syndrome" (approx. 12% of the cases described). The boy finally recovered after receiving Cotrimoxacol (20 mg/kg bw/d) in an intensive care unit. Now, at the age of nearly two his condition is almost good under regular substitution of IgG. Cotrimoxacol (4 mg/kg bw/d) is recommended to prevent further pneumocystis carinii infections and most of the pathogenes which frequently appear in neutropenias.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Follow-Up Studies; Humans; Hypergammaglobulinemia; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infant; Male; Neutropenia; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Bacterial Infections; Cohort Studies; Female; HIV Infections; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

An unusual acute hypotensive syndrome has been observed in association with administration of trimethoprim-sulfamethoxazole (TMP-SMZ) to patients with human immunodeficiency virus (HIV) infection. In the 11 cases that have been reported, the syndrome differs from classic anaphylaxis and resembles septic shock. Mediation by tumor necrosis factor (TNF) has been hypothesized, but the mechanism has not been characterized with cytokine assays, and no invasive hemodynamic measurements have been reported. We describe a case of recurrent hyperdynamic shock--without classic features of anaphylaxis, without detectable IgE antibodies against TMP or SMZ, and without detectable levels of TNF--involving an HIV-infected patient rechallenged with TMP-SMZ.

Topics: Adult; AIDS-Related Opportunistic Infections; Anaphylaxis; Complement System Proteins; Fever; Hemodynamics; Humans; Hypotension; Interleukin-6; Male; Pneumonia, Pneumocystis; Shock; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

To determine the effect of trimethoprimsulfamethoxazole (Tmp-Smx) on serum potassium concentration.. Retrospective cohort study.. An urban teaching hospital.. Fifty-one persons hospitalized for symptomatic infection with human immunodeficiency virus (HIV). Twenty-five patients who were taking high-dose Tmp-Smx (trimethoprim 20 mg/kg per day; sulfamethoxazole, 100 mg/kg per day) for Pneumocystis carinii pneumonia were the study group. Twenty-six patients who had not received the drug were the control group. Patients who received potassium supplements, those taking medications known to alter potassium homeostasis or renal function, or those with a serum creatinine level more than 186 mumol/L were excluded.. Serum potassium concentration in the study group was 4.1 +/- 0.1 mmol/L (mean +/- SE) and increased by 1.1 mmol/L (Cl, 0.8 to 1.5 mmol/L) (P < 0.0001) 9.8 +/- 0.5 days after starting Tmp-Smx therapy. Patients followed longitudinally showed a progressive increase in serum potassium levels during therapy and a progressive decline after discontinuing Tmp-Smx. Blood urea nitrogen and serum creatinine levels increased mildly from 4.3 +/- 0.5 mmol/L and 85 +/- 6 mumol/L to 6.4 +/- 0.7 mmol/L and 113 +/- 8 mumol/L, respectively. The serum potassium level in the control group was 4.3 +/- 0.1 mmol/L and remained unchanged during hospitalization.. High-dose Tmp-Smx therapy used for the treatment of P. carinii pneumonia in HIV-infected patients leads to an increase in the serum potassium concentration and may result in life-threatening hyperkalemia. Patients receiving high doses of Tmp-Smx require close monitoring of their serum potassium concentration, particularly 7 to 10 days after the start of therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Cohort Studies; Female; Humans; Hyperkalemia; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The outcomes of alternative strategies for the management of pulmonary complications in patients infected with the human immunodeficiency virus (HIV) and with suspected Pneumocystis carinii pneumonia were compared using a decision analysis model. A decision tree was constructed using baseline probabilities derived from published data and expert opinion. The case scenario analyzed was that of a patient not currently receiving anti-Pneumocystis prophylaxis who presents with moderate pulmonary symptoms and fulfills the Centers for Disease Control (CDC) criteria for presumptive P. carinii pneumonia. Two strategies were compared: (1) early bronchoscopy with appropriate therapy based on the results, and (2) empiric treatment for P. carinii (trimethoprim/sulfamethoxazole or pentamidine, and steroids) with delayed bronchoscopy in those not responding to 5 days of empiric therapy. The expected 1-month survival rate (with and without quality of life adjustment) was found to be essentially the same for the two strategies using the baseline probabilities, and the decision remained a toss-up within the clinically relevant range of published probabilities for P. carinii pneumonia in patients fulfilling the CDC criteria. Because early bronchoscopy does not offer any additional survival benefits and is associated with greater costs and disutility, empiric therapy would appear to be the superior management strategy in this scenario.

Topics: AIDS-Related Opportunistic Infections; Biopsy; Bronchi; Bronchoalveolar Lavage Fluid; Bronchoscopy; Decision Support Techniques; Decision Trees; HIV Seropositivity; Humans; Lung Diseases; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Prevalence; Probability; Quality of Life; Sensitivity and Specificity; Survival Rate; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Angiography; Choroiditis; Humans; Male; Pneumocystis Infections; Pneumonia, Pneumocystis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

A newly synthesized biguanide inhibitor of dihydrofolate reductase in Plasmodium species was evaluated for its anti-Pneumocystis carinii activity. The compound N-3-(2,4,5-trichlorophenoxypropyloxy)-N'-(1-methylethyl)imidoca rbonimidic diamide hydrochloride, designated PS-15, was administered prophylactically and therapeutically to immunosuppressed rats latently infected with P. carinii. Doses of 5 and 25 mg of PS-15 per kg of body weight per day given orally during 7 weeks of dexamethasone immunosuppression prevented P. carinii infection in all (100%) 19 rats given the drug, while 6 of 9 (67%) untreated control rats developed P. carinii pneumonitis. A single weekly dose of 50 mg of PS-15 per kg also prevented the infection in all 10 rats. P. carinii pneumonitis was established after 4 weeks of immunosuppression and was then treated orally for 3 weeks with 25, 5, and 1 mg of PS-15 per kg/day. Complete resolution of the infection occurred in all (100%) 10 rats given 25 mg of PS-15, 6 of 9 (67%) rats given 5 mg of PS-15, and 6 of 8 (75%) rats given 1.0 mg of PS-15 per kg per day and in all (100%) 9 rats treated with trimethoprim-sulfamethoxazole. PS-15 was well tolerated at all doses. Because drug studies in the P. carinii rat model have been highly predictable of the effects of drugs on the disease in humans, these experiments suggest that PS-15 may have promise as a drug for the treatment of P. carinii pneumonitis in humans.

Topics: AIDS-Related Opportunistic Infections; Animals; Antimalarials; Dose-Response Relationship, Drug; Folic Acid Antagonists; Imides; Immunosuppressive Agents; Lung; Male; Phenyl Ethers; Pneumocystis Infections; Pneumonia, Pneumocystis; Proguanil; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; Trimethoprim, Sulfamethoxazole Drug Combination

We have described an exogenously immunosuppressed, HIV-negative patient with a subacute presentation of Pneumocystis carinii pneumonia characterized by normal arterial oxygen tension and alveolar-arterial oxygen gradient and normal findings on serial chest radiographs. This case demonstrates that other studies in addition to chest radiograph and resting arterial blood gas measurement are necessary in all immunosuppressed patients with progressive respiratory symptoms, regardless of cause of immunosuppression, to exclude P carinii pneumonia from the differential diagnosis.

Topics: Adult; Female; Humans; Immunosuppression Therapy; Kidney Transplantation; Oxygen; Pancreas Transplantation; Pneumonia, Pneumocystis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

A group of clinical, immunologic, and virologic variables was examined to determine if any predicted the development of hypersensitivity to trimethoprim-sulfamethoxazole (TMP-SMZ) during treatment of Pneumocystis carinii pneumonia in patients with human immunodeficiency virus (HIV) infection. Hypersensitivity occurred in 39 (27%) of 143 patients, who had significantly higher total lymphocyte and CD4+ and CD8+ cell counts and CD4:CD8 ratios than did those who did not develop hypersensitivity. Regression analysis identified having a CD4:CD8 ratio > 0.10 (95% confidence interval [CI], 1.75-3.94; P = .02) and treatment for < 14 days (95% CI, 1.57-3.75; P = .04) as independently predictive of hypersensitivity. Use of corticosteroids tended to reduce the frequency of hypersensitivity (7% vs. 30%; P = .07). T lymphocytes may be important in the pathogenesis of these hypersensitivity reactions. As the frequency of hypersensitivity declines with disease progression, T lymphocytes could be effector cells in these reactions or their sensitivity to TMP-SMZ may decline with HIV disease progression.

Topics: Adrenal Cortex Hormones; Adult; Aged; AIDS-Related Opportunistic Infections; Antibodies, Viral; CD4-CD8 Ratio; Cytomegalovirus Infections; Drug Hypersensitivity; Humans; Immunoglobulins; Male; Middle Aged; Pneumonia, Pneumocystis; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

Seven cases of single lung transplantation are reported. The recipients were all below 60 years of age and severely disabled with end-stage lung disease. Transplantation was performed according to ABO blood group compatibility and negative lymphocytotoxic cross-match between donor and recipient irrespective of HLA mismatch. Recipients' diagnoses were sarcoidosis (3), alfa-1 antitrypsin deficiency (3), and idiopathic emphysema (1). Mean recipient age was 48 +/- 2.4 years (range 45-52). Donor age was 29.7 +/- 5.6 years (range 16-49). The immunosuppressive regimen included cyclosporin A, azathioprine, steroids and rabbit antithymocyte globulin. Excellent graft function was achieved. Six patients survived the postoperative period and are alive 4-18 months posttransplant. One patient died after the operation due to pneumonia with respiratory distress syndrome. Graft function was also monitored by transbronchial biopsy, and 57 biopsy procedures were performed without fatal complications. Acute cellular rejection was seen in 16 biopsy specimens from 5 recipients (grade 1 and 2 rejection in 14, grade 3 rejection in 2). Neither severe rejection with septal necrosis (grade 4) nor obliterative bronchiolitis was seen. The rejection rate was 0.03 episodes per patient/month. In contrast to other reports, episodes of cellular rejection occurred throughout the observation period, and were not mainly limited to the first 4 months posttransplant. Graft vascular occlusive disease or chronic vascular rejection was found in 6 biopsy specimens from one recipient. Five patients experienced 7 episodes of cytomegalovirus infection. The cytomegalovirus infection rate was 0.01 episodes per patient/month. The incidence of infection was significantly lower compared to previous studies of rejection in other lung graft combinations. Both infections and rejection episodes may contribute to the development of obliterative bronchiolitis. Almost one third of the specimens (30%) showed lymphocytic bronchitis without perivascular inflammation. The absence of perivascular infiltrates and exclusion of infectious agents leaves in question the aetiology of this inflammation. The lymphocytic bronchitis could be ischaemic, related to aspiration, or represent recurrent sarcoidosis, or, in fact, express bronchial rejection. All biopsy specimens regarded as rejection with cellular infiltrates in the lung parenchyma also showed a lymphocytic bronchitis. The impact of HLA mismatch on cellular and vascu

Topics: Adult; alpha 1-Antitrypsin Deficiency; Biopsy, Needle; Bronchiolitis; Cytomegalovirus Infections; Emphysema; Female; Ganciclovir; Graft Rejection; Humans; Immunosuppression Therapy; Lung; Lung Diseases, Fungal; Lung Transplantation; Male; Middle Aged; Pneumonia, Pneumocystis; Respiratory Insufficiency; Sarcoidosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Inhalation; Aerosols; AIDS-Related Opportunistic Infections; Child, Preschool; Dapsone; Drug Administration Schedule; Humans; Injections, Intravenous; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Time Factors; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Dapsone; Humans; Pneumonia, Pneumocystis; Research Design; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Drug Hypersensitivity; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Alanine Transaminase; Aspartate Aminotransferases; Bilirubin; Cholestasis; Giant Cells; Hepatitis, Viral, Human; Hepatomegaly; HIV Infections; HIV Seropositivity; Humans; Infant; Liver; Pentamidine; Pneumonia, Pneumocystis; Splenomegaly; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Antifungal Agents; Atovaquone; Clinical Trials as Topic; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Atypical pulmonary manifestations of Pneumocystis carinii infection and fair numbers of extrapulmonary and disseminated infections have lately been documented in patients with human immunodeficiency virus infection treated prophylactically with inhalative pentamidine. We report the case of a 32-year-old homosexual patient who was assessed for complaints of night sweats, weight loss, and progressive malaise. The patient denied any respiratory tract symptoms such as cough, sputum production, pleuritic chest pain, or shortness of breath. Chest X-ray revealed two large round noncavitating lesions in the lower lobe of the right lung. Pneumocystomas were diagnosed by fine-needle aspiration. A 3-week course of intravenous high-dose cotrimoxazole resulted in amelioration of symptoms but no change in the radiographic appearance of the pulmonary lesions. Four months later the patient is alive and stable and is being treated with pentamidine inhalation of 300 mg per 2 weeks and two tablets of pyrimethamine sulfadoxine per week.

Topics: Administration, Inhalation; Adult; AIDS-Related Opportunistic Infections; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aerosols; AIDS-Related Opportunistic Infections; Humans; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the negative predictive value of bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia (PCP) during prophylaxis with aerosolized pentamidine. On the basis of the assumption that undiagnosed and untreated PCP would progress and become clinically apparent, for 3 months we prospectively followed 34 consecutive cases in which BAL had not detected PCP. All patients were immunodeficient, had a symptomatic human immunodeficiency virus infection, and were evaluated for possible PCP during prophylaxis with aerosolized pentamidine. No transbronchial biopsies were performed. In 32 of 34 cases, a diagnosis of PCP could be excluded because of other definite diagnoses or improvement during the follow-up. Despite negative results of an examination of their BAL fluid, two patients received empirical treatment that was active against PCP; these patients were regarded as possibly having undiagnosed PCP. Thus, the negative predictive value of BAL alone was at least 94% (32 of 34 cases) in excluding a diagnosis of PCP during prophylaxis with aerosolized pentamidine.

Topics: Administration, Intranasal; Adult; Aerosols; AIDS-Related Opportunistic Infections; Bronchoalveolar Lavage Fluid; Dapsone; Female; Follow-Up Studies; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Predictive Value of Tests; Prospective Studies; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Therapy; Humans; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination