trimethoprim--sulfamethoxazole-drug-combination and Pneumocystis-Infections

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

Topics: Acidosis; Aged; Anti-Infective Agents; Anuria; Arthritis, Rheumatoid; Coma; Emergencies; Humans; Hyperkalemia; Hypoglycemia; Kidney Failure, Chronic; Male; Myocardial Ischemia; Pneumocystis Infections; 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

Co-trimoxazole is a frequently prescribed antibiotic worldwide. It is composed of both trimethoprim and sulfamethoxazol (Sfx) and is used in the treatment and prophylaxis of urinary tract and Pneumocystis jirovecii infections. The Sfx component appears to be nephrotoxic at high doses or doses inappropriately adjusted for glomerular filtration rate (GFR). The trimethoprim component, even at recommended doses, inhibits tubular creatinine secretion, leading to a rapid but ultimately reversible increase in serum creatinine independent of any changes in GFR. This translates into a falsely low estimated GFR when creatinine-based equations are used. This review focuses on evidence of the differential effects of trimethoprim and Sfx on serum creatinine concentrations and GFR and their relevance to clinical practice, with particular attention to kidney transplantation.

Topics: Anti-Infective Agents, Urinary; Creatinine; Glomerular Filtration Rate; Humans; Kidney Transplantation; Pneumocystis carinii; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

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

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

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

Pneumocystis carinii (PC) otitis is a rare opportunistic infection of the acquired immunodeficiency syndrome (AIDS). Initially hearing loss and otalgia occur with thickening of the tympanic membrane and the bordering skin of the ear canal. Otorrhea, ear polyps, perforation of tympanic membrane, destruction of mastoidal bone, and participation of cranial nerves are observed. Diagnosis is established histologically. The treatment of the parasite is by trimethoprim-sulfamethoxazole combinations. The immunological situation seems to be better than in PC pneumonia. Due to the underlying immunological incompetence the infection can not be expected to limit itself. To prevent severe complications as sequestrating mastoiditis, early diagnosis and specific surgical and medical treatment are necessary.

Topics: Adult; AIDS-Related Opportunistic Infections; Combined Modality Therapy; Diagnosis, Differential; Ear, Middle; Humans; Male; Otitis; Otitis Media; Pneumocystis Infections; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Cyclosporine is a fungal metabolite and a powerful immunosuppressant. While response to intravenous steroids in severe ulcerative colitis is in excess of 60%, the remainder of patients are left with the options of curative panproctocolectomy or administration of intravenous rescue therapy with cyclosporine. There have been conflicting reports on the efficacy of intravenous cyclosporine in acute ulcerative colitis, and there are serious concerns about potential toxicity and opportunistic infections such as Pneumocystis carnii pneumonia. There are also concerns about early relapse and colectomy following cyclosporine rescue. To date there has been a paucity of data available to help guide the gastroenterologist in the use of cyclosporine and the maintenance of remission once achieved.. Between 1994 and 2001, a total of sixteen patients who had received intravenous cyclosporine for acute exacerbation of their known UC (seven females, nine males, mean age 33 years) whose records were available for analysis. All patients were refractory to intravenous methylprednisolone (60 mg/24 h). Patients who responded to cyclosporine were discharged on a regimen of oral cyclosporine, oral steroids oral azathioprine and 5-aminosalicylate.. Median disease duration was 5.4 years (range 0.9-25 years). All sixteen patients were initially treated with cyclosporine at a dose of 4 mg/kg/day. Nine patients were started on oral azathioprine (median dose 1.8 mg/kg). Seven patients underwent surgery (panproctocolectomy), although none had surgery after 6 months. Comparisons were made between patients with <7 days and >7 days intravenous steroid. Other parameters analysed were stool frequency at 3 days and CRP at 3 days. There were no significant differences between these groups. Median bowel frequency at day 3 was higher in patients who finally underwent surgery. At 3 years follow-up, 56% of the sixteen patients had avoided surgery by using azathioprine immunosuppression.. The initial response rate to intravenous cyclosporine was high (69%). Side effects were documented in the majority of patients, but none of the patients had to discontinue treatment on account of these. Azathioprine has a useful role in maintaining the remission achieved by i.v. cyclosporine for acute ulcerative colitis patients. More than half the patients will avoid colectomy long-term when using triple immunosuppressive therapy including azathioprine adding support for its relative safety and another role for its use.

Topics: Administration, Oral; Adult; Anti-Infective Agents; Azathioprine; Colitis, Ulcerative; Cyclosporine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Infusions, Intravenous; Injections, Intravenous; Male; Methylprednisolone; Pneumocystis Infections; Prednisolone; Salvage Therapy; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

One hundred and thirty-nine consecutive episodes of fever were evaluated in 55 patients with hematological disorders during persistent neutropenia. In 121 instances, patients were given trimethoprim-sulfamethoxazole + amikacin (TMP/SMZ + AMI) as an initial antibiotic regimen with clinical success in 51% (i.e. antibiotic treatment was not changed within the first 7 days). Imipenem/cilastatin (I/C) therapy was instituted in: (a) 22 episodes with clinical failure and fever of unknown origin during TMP/SMZ + AMI therapy and (b) 18 episodes with a second fever episode during initially successful TMP/SMZ + AMI therapy. The response rate for all 40 I/C treated episodes was 80%. One neutropenic patient in the whole series died from infectious complications within four weeks from institution of therapy. TMP/SMZ+AMI seems to be a safe and inexpensive "standard" antibiotic regimen in neutropenic patients. I/C appears to have good efficacy when used as secondary therapy after failure with TMP/SMZ+AMI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Bacterial Infections; Bone Marrow Transplantation; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Fever; Hematologic Diseases; Humans; Imipenem; Leukemia; Lymphoma; Male; Middle Aged; Neutropenia; Pneumocystis Infections; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Asthma; Child; Female; Humans; Lung; Male; Pneumocystis; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) remains a debilitating cause of death among HIV-infected patients. The combination trimethoprim/sulfamethoxazole (SXT) is the most effective anti-Pneumocystis treatment and prophylaxis. However, long-term use of this combination has raised alarms about the emergence of resistant organisms. This study was performed to investigate mutations in the dihydropteroate synthase (DHPS) gene and their clinical consequences in HIV-infected patients with PCP.. A total of 76 clinically suspected cases of PCP among HIV-seropositive adult patients from March 2014 to March 2017 were included. Clinical samples (bronchoalveolar lavage fluid and sputum) were investigated for the detection of Pneumocystis jirovecii using both microscopy and nested PCR. DHPS genotyping and mutational analyses were performed and the data were correlated with clinical characteristics.. This study suggests that the emergence of a mutant P. jirovecii genotype is probably associated with drug resistance and mortality. The data also suggest that DHPS mutational analyses should be performed in HIV-seropositive patients to avoid treatment failure and death due to PCP. However, the role of underlying disease severity and co-morbidities should not be underestimated.

Topics: Adult; Aged; Bronchoalveolar Lavage Fluid; Coinfection; Dihydropteroate Synthase; DNA Mutational Analysis; Drug Resistance, Fungal; Drug Resistance, Multiple, Bacterial; Female; Genotype; HIV Infections; Humans; India; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumocystis Infections; Polymerase Chain Reaction; Sputum; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Despite antiretroviral therapy and trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, Pneumocystis pneumonia remains an important serious opportunistic infection in HIV-infected persons. Pneumocystis (Pc) colonization in HIV-infected individuals and in HIV-uninfected smokers is associated with chronic obstructive pulmonary disease (COPD). We previously developed a nonhuman primate model of HIV infection and Pc colonization and demonstrated that Pc colonization correlated with COPD development. In the present study, we examined kinetics of COPD development in non-human primate and tested the effect of Pc burden reduction on pulmonary function by TMP-SMX treatment.. Cynomolgus macaques (n = 16) were infected with simian/human immunodeficiency virus (SHIV89.6P), and natural Pc colonization was examined by nested polymerase chain reaction of serial bronchoalveolar lavage fluid and anti-Pc serology.. Eleven of 16 monkeys became Pc colonized by 16 weeks post simian-human immunodeficiency virus (SHIV) infection. Pc colonization of SHIV-infected monkeys led to progressive declines in pulmonary function as early as 4 weeks after Pc detection. SHIV-infected and Pc-negative monkeys maintained normal lung function. At 25 weeks post-SHIV infection, TMP-SMX treatment was initiated in 7 Pc-positive (Pc+) (TMP: 20 mg/kg and SMX: 100 mg/kg, daily for 48 weeks) and 5 Pc-negative (Pc-) monkeys. Four SHIV+/Pc+ remained untreated for the duration of the experiment. Detection frequency of Pc in serial bronchoalveolar lavage fluid (P < 0.001), as well as plasma Pc antibody titers (P = 0.02) were significantly reduced in TMP-SMX-treated macaques compared with untreated.. Reduction of Pc colonization by TMP-SMX treatment did not improve pulmonary function, supporting the concept that Pc colonization results in early, permanent obstructive changes in the lungs of immunosuppressed macaques.

Topics: Animals; Anti-Infective Agents; Antibodies, Fungal; Bronchoalveolar Lavage Fluid; Lung Diseases, Obstructive; Macaca; Pneumocystis; Pneumocystis Infections; Polymerase Chain Reaction; Simian Acquired Immunodeficiency Syndrome; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Blood Glucose; Burkitt Lymphoma; CD4 Lymphocyte Count; Chromatography, High Pressure Liquid; Dapsone; Diabetes Mellitus, Type 2; Drug Interactions; Folic Acid Antagonists; Glycated Hemoglobin; HIV Infections; Humans; Male; Middle Aged; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia (PCP) is an important cause of morbidity and mortality in renal transplant recipients (RTRs). Chemoprophylaxis with trimethoprim/sulphamethoxazole is recommended during the early post-transplantation period, but the optimal duration has not been determined and a main drawback of chemoprophylaxis is the development of resistance of the commensal faecal flora. A cluster outbreak of PCP occurred in our outpatient Renal Transplant Unit. We aimed to investigate risk factors for PCP in RTRs to determine who should receive long-term chemoprophylaxis.. In a case-control study, we investigated common demographic variables and immunological parameters. Nine PCP cases diagnosed between August 2006 and April 2007 were matched with 18 control patients, who did not develop PCP, received their transplant in the same time-period and had a similar follow-up period with a comparable immunosuppressive drug regimen.. The median time from transplantation to PCP was 19 months. We observed no significant differences in gender, age, donor type or number of rejections. In PCP cases, the median lymphocyte count just before PCP diagnosis was 0.49 (0.26-0.68), which was significantly reduced compared to the control patients after a similar follow-up period (median 1.36, 0.59-3.04, P = 0.002). This lymphocytopaenia was chronic and existed in most patients already for many months. CD4(+) T-cell counts were also significantly reduced in the PCP cases. We found no difference in the Th1, Th2 and Th17 subsets between PCP cases and control patients.. Long-term prophylactic therapy for PCP may be indicated for RTR with persistent severe lymphocytopaenia.

Topics: Adult; Aged; Anti-Infective Agents; Case-Control Studies; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Lymphocyte Count; Lymphopenia; Male; Middle Aged; Pneumocystis carinii; Pneumocystis Infections; Prognosis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia (PCP) is a serious complication in patients receiving chemotherapy or hematopoietic stem cell transplantation. Current recommendations for trimethoprim-sulfamethoxazole (TMP-SMZ) dosing as PCP prophylaxis in immunocompromised patients are based on either daily dosing or dosing three consecutive days per week. We report our experience of prophylaxis with TMP-SMZ twice daily on two non-consecutive days per week in 145 immunocompromised children with hematologic disorders, cancer, or metabolic disorders following chemotherapy or hematopoietic stem cell transplantation. There were no breakthrough cases of PCP. We therefore conclude our prophylaxis regimen is effective against PCP in immunocompromised children.

Topics: Antineoplastic Agents; Child; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Pneumocystis Infections; Premedication; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antifungal Agents; Atovaquone; Female; HIV; HIV Infections; Humans; Immunohistochemistry; Pentamidine; Pneumocystis carinii; Pneumocystis Infections; Polymerase Chain Reaction; Spleen; Splenic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ transplantation. An elevated serum lactate dehydrogenase (LDH) is a marker of PTLD activity. We report the case of a 58-year-old female renal transplant patient with a prior history of extranodal PTLD, which developed 19 years after a second transplant. She was successfully treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) and maintained subsequently on sirolimus and prednisone. She presented 3 years later with fever, dyspnea, cough, lung infiltrates and elevated serum LDH concerning for recurrence of PTLD. Bronchoscopy revealed Pneumocystis carinii (jiroveci) pneumonia. The patient was treated with trimethoprim-sulfamethoxazole, but developed nausea and was converted to dapsone. The patient was readmitted 4 weeks later with increasing dyspnea and hypoxemia and found to have a methemoglobin level of 16%. Dapsone was discontinued with resolution of all symptoms. We discuss the diagnostic and clinical challenges in this complex case.

Topics: Anti-Infective Agents; Biomarkers; Dapsone; Female; Humans; Kidney Transplantation; L-Lactate Dehydrogenase; Lymphoproliferative Disorders; Middle Aged; Pneumocystis Infections; Postoperative Complications; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

AIDS-associated otic pneumocystosis is rare. Of 14 cases documented mainly as case reports up to now, only 1 has been reported in the surgical pathology literature. We report 6 males, mean age of 32.3 years, with external auditory canal masses and otorrhea. Two biopsies contained a predominance of granulation tissue with a mixed inflammatory cell infiltrate and elusive foci of foamy exudate. In contrast, 4 biopsies demonstrated conspicuous angiocentric mantles of stippled, foamy exudate. Fibrin was noted in intravascular, perivascular, and intervascular locations. One biopsy demonstrated bordering of the foamy exudate by a palisaded granulomatous reaction, with adjacent discrete giant cell-containing granulomas. Special stains confirmed trophozoites and cysts within the foamy exudate. Review of 2 initial "nondiagnostic" biopsies confirmed granulation tissue and necrotic debris in which Pneumocystis jiroveci was identified in focal foamy exudate. After the diagnosis of otic pneumocystosis, all patients were initiated on trimethoprim-sulfamethoxazole. One patient also had dapsone. Two patients succumbed to pulmonary tuberculosis and 2 were lost to follow-up. One patient with pneumocystis pneumonia did not return for follow-up after 6 weeks. One patient experienced complete resolution of the mass on medical therapy, and is disease free for 4 years. Heightened recognition of the characteristic foamy exudate in an unconventional location remains the gold standard in the timely diagnosis of this eminently treatable disease. In all patients, otic pneumocystosis served as the sentinel of underlying HIV infection and AIDS.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dapsone; Drug Therapy, Combination; Fatal Outcome; Humans; Immunocompromised Host; Male; Otitis Media; Pneumocystis Infections; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Most drugs used for prevention and treatment of Pneumocystis jirovecii pneumonia target enzymes involved in the biosynthesis of folic acid, i.e., dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR). Emergence of P. jirovecii drug resistance has been suggested by the association between failure of prophylaxis with sulfa drugs and mutations in DHPS. However, data on the occurrence of mutations in DHFR, the target of trimethoprim and pyrimethamine, are scarce. We examined polymorphisms in P. jirovecii DHFR from 33 patients diagnosed with P. jirovecii pneumonia who were receiving prophylaxis with a DHFR inhibitor (n = 15), prophylaxis without a DHFR inhibitor (n = 11), or no prophylaxis (n = 7). Compared to the wild-type sequence present in GenBank, 19 DHFR nucleotide substitution sites were found in 18 patients with 3 synonymous and 16 nonsynonymous mutations. Of 16 amino acid changes, 6 were located in positions conserved among distant organisms, and five of these six positions are probably involved in the putative active sites of the enzyme. Patients with failure of prophylaxis, including a DHFR inhibitor, were more likely to harbor nonsynonymous DHFR mutations than those who did not receive such prophylaxis (9 of 15 patients versus 2 of 18; P = 0.008). Analysis of the rate of nonsynonymous versus synonymous mutations was consistent with selection of amino acid substitutions in patients with failure of prophylaxis including a DHFR inhibitor. The results suggest that P. jirovecii populations may evolve under selective pressure from DHFR inhibitors, in particular pyrimethamine, and that DHFR mutations may contribute to P. jirovecii drug resistance.

Topics: Adult; Amino Acid Sequence; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Cloning, Molecular; DNA, Fungal; Drug Resistance, Fungal; Evolution, Molecular; Female; Folic Acid Antagonists; HIV Infections; Humans; Male; Middle Aged; Molecular Sequence Data; Mutation; Plasmids; Pneumocystis; Pneumocystis Infections; Pyrimethamine; Reverse Transcriptase Polymerase Chain Reaction; Tetrahydrofolate Dehydrogenase; Trimethoprim, Sulfamethoxazole Drug Combination

Isolates of Pneumocystis jiroveci from sulfa-exposed and nonexposed patients from London, United Kingdom, and Harare, Zimbabwe, were genotyped. At the dihydropteroate synthase (DHPS) locus, there was evidence of selection pressure from sulfa drug exposure, and reversal of DHPS genotype ratios occurred when selection pressure was absent or was removed.

Topics: Genotype; HIV Infections; HIV-1; Humans; London; Mycoses; Pneumocystis; Pneumocystis Infections; Reverse Transcriptase Polymerase Chain Reaction; RNA, Ribosomal; RNA, Viral; Trimethoprim, Sulfamethoxazole Drug Combination; United Kingdom; Zimbabwe

Children with acute lymphoblastic leukaemia (ALL) are treated with intensive chemotherapy, which results in profound immunosuppression. Treatment with trimethoprim/sulphamethoxazole (TMP-SMX) is therefore used in some departments as prophylaxis against infections with both bacteria and Pneumocystis carinii. The use of TMP/SMX for prophylaxis during the induction therapy is not uniform in the four departments of paediatric oncology in Denmark. This gave us the opportunity to describe the effect of TMP/SMX on bacterial infections in children with ALL during the induction therapy.. Between 1 January 1992 and 31 December 1997, 210 children were diagnosed with ALL in Denmark. From a retrospective review of the medical charts, the number of children with fever (> 38 degrees C), the number of febrile days, days of antibiotic treatment, and the number of positive blood cultures were registered for each febrile episode.. One hundred and fourteen children received TMP/SMX prophylaxis (10-30 mg/SMX/kg/day) and 76 did not. Children who received TMP/SMX prophylaxis had significantly fewer episodes of fever (66/114 (58%) vs. 60/76 (79%), p < 0.01) and significantly fewer children who received the prophylaxis had positive blood cultures before the start of antibiotic treatment compared with children who did not receive prophylaxis (23/114 (20%) vs 37/76 (49%), p < 0.001)). Nineteen different species were isolated from the blood stream before the start of antibiotic treatment. In the non-prophylaxis group there were a preponderance of isolates with Staph. aureus, Str. pneumoniae, E. coli, and P. aeruginosa. There was no difference in the mortality between the two groups (p = 0.44). There were no cases of P. carinii pneumonia in the period of induction therapy.. TMP/SMX prophylaxis during induction therapy for childhood ALL seems to reduce the risk of bacteraemias and febrile illness.

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Bacteremia; Child; Child, Preschool; Denmark; Drug Therapy, Combination; Female; Humans; Immunocompromised Host; Infant; Male; Opportunistic Infections; Pneumocystis Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

A review was undertaken of the clinical features and results of diagnostic tests in non-HIV infected patients who developed granulomatous Pneumocystis carinii pneumonia (PCP).. A retrospective review was performed of the charts and radiographs of patients with a granulomatous reaction to P carinii identified from computerised pathology records at Memorial Sloan Kettering Cancer Center, a university affiliated tertiary care hospital.. Three cases were identified; the incidence of granulomatous PCP was 3%. All patients had risk factors for PCP and had received high dose corticosteroids which had been stopped. Two patients had received chemotherapy. Presentation was insidious with only mild symptoms; only one patient had fever. Chest radiographs showed a reticulonodular pattern. Bronchoscopy was negative for PCP in all cases and open lung biopsy was necessary.. A granulomatous pathological reaction to PCP occurs rarely in patients with malignancy. In these cases the clinical presentation may be atypical and bronchoscopy can be non-diagnostic.

Topics: Adolescent; Adult; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Female; Glioblastoma; Granuloma; Hodgkin Disease; Humans; Male; Middle Aged; Pneumocystis Infections; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Children with acute lymphoblastic leukemia are treated with intensive chemotherapy resulting in profound immuno suppression. Therefore treatment with trimethoprim-sulfamethoxazole (TMP-SMX) may be used for prophylaxis against infections both with bacteria and Pneumocystis carinii in some departments. The use of TMP-SMX for prophylaxis during the induction therapy is not uniform in the four departments of pediatric oncology in Denmark. This gave us the opportunity to describe the effect of TMP/SMX on bacterial infections in children with ALL during the induction therapy.. Between January 1st 1992 and December 31st 1997, 210 children were diagnosed with ALL in Denmark. Based on a retrospective review of the medical charts the number of children with fever (>38 degrees C), the number of febrile days, days of antibiotic treatment and the number of positive blood cultures were registered for every febrile episode.. One hundred and fourteen children received TMP/SMX prophylaxis (10-30 mg/SMX/kg/day) and 76 did not. Children who received TMP/SMX prophylaxis had significantly fewer episodes of fever (66/114 (58%) v 60/76 (79%), p <0,01), and significantly fewer children who received TMP/SMX prophylaxis had positive blood cultures before start of antibiotic treatment compared with children who did not receive prophylaxis (23/114 (20%) vs 37/76 (49%), p<0.001)). Nineteen different species were isolated from the blood stream before start of antibiotic treatment. In the non-prophylaxis group there was a preponderance of isolates with Staph. aureus, Str. pneumoniae, E. coli and P. aeruginosa. There was no difference in the mortality between the two groups (p=0.44). There were no cases of P carinii pneumonia in the period of induction therapy.. TMP/SMX prophylaxis during induction therapy for childhood ALL seems to reduce the risk of bacteremias and febrile illness.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Child, Preschool; Female; Humans; Immunocompromised Host; Male; Opportunistic Infections; Pneumocystis Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

New analogues of the venerable antimalarial drug primaquine have been synthesized and bioassayed in vivo against Pneumocystis carinii, a life-threatening infection common among immunosuppressed patients. Two of these new compounds are significantly more active than primaquine itself, and provide new information for future drug design and development in this area.

Topics: Animals; Antifungal Agents; Dose-Response Relationship, Drug; Drug Design; Female; Humans; Molecular Structure; Pneumocystis; Pneumocystis Infections; Primaquine; Rats; Structure-Activity Relationship

Topics: Drug Hypersensitivity; Follow-Up Studies; HIV Infections; Humans; Immune Tolerance; Pneumocystis Infections; Therapeutic Equivalency; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

In the setting of organ transplantation, prior to prophylaxis, Pneumocystis carinii pneumonia (PCP) had been a common clinical problem, particularly in heart-lung and lung recipients who receive long-term immunosuppressive therapy to prevent allograft rejection. Continuous oral trimethoprim-sulfamethoxazole (TMP-SMX) has been highly effective in preventing PCP in these patients.. In this paper we report a case of recurrent Pneumocystis carinii infection in a chronic (> 15 years) heart-lung allograft recipient on long-term TMP-SMX prophylaxis. Twice, in 1995 and again in 1998, Pneumocystis carinii infection was diagnosed by bronchoalveolar lavage (BAL), in the same patient, despite continued oral TMP-SMX (960 mg TMP/4800 mg SMX per week) prophylaxis. The subject was not lymphopenic (his CD4 count was 569/mm3) and there was no associated deterioration in pulmonary function, nor evidence of hypoxemia.. This case demonstrates that asymptomatic Pneumocystis carinii lung infections may recur in chronic heart-lung transplant recipients who take standard oral PCP prophylaxis.

Topics: Administration, Oral; Anti-Bacterial Agents; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; CD4 Lymphocyte Count; Clindamycin; Forced Expiratory Volume; Heart-Lung Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Opportunistic Infections; Pneumocystis; Pneumocystis Infections; Pulmonary Gas Exchange; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination; Vital Capacity

The results of multicenter clinical trials may differ across participating clinical sites. We present a diagnostic approach for evaluating this diversity that emphasizes the relationship between the observed event rates and treatment effects. We use as an example a trial of sequential strategies of Pneumocystis prophylaxis in human immunodeficiency virus infection with 842 patients randomly allocated to start prophylaxis with trimethoprim/sulfamethoxazole, dapsone, or pentamidine. Prophylaxis failure rates varied significantly across the 30 clinical sites (0-30.3%, p = 0.002 by Fisher's exact test) with prominent variability in the pentamidine arm (0-63.6%). Starting with oral regimens was better than starting with pentamidine in sites with high rates of events, whereas the three strategies had more similar efficacy in other sites. Sites enrolling fewer patients had lower event rates and had more patients who withdrew prematurely or were lost to follow-up. In a hierarchical regression model adjusting for random measurement error in the observed event rates, starting with trimethoprim/sulfamethoxazole was predicted to be increasingly better than starting with aerosolized pentamidine as the risk of prophylaxis failure increased (p = 0.01), reducing the risk of failure by 47% when the failure rate of pentamidine was 30%, whereas the two regimens were predicted to be equivalent when the failure rate was 17%. Differences in event rates could reflect a combination of heterogeneity in diagnosis, administration of treatments, and disease risk in patients across sites. The evaluation of clinical site differences with a systematic approach focusing on event rates may give further insight in the interpretation of the results of multicenter trials beyond an average treatment effect.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Controlled Clinical Trials as Topic; Dapsone; Humans; Multicenter Studies as Topic; Pentamidine; Pneumocystis Infections; Probability; Proportional Hazards Models; Sample Size; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Brain; Child; Fatal Outcome; HIV Seropositivity; Humans; Male; Phenotype; Pneumocystis Infections; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

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

In hospitals attended by patients with human immunodeficiency virus infection, adverse reactions are often observed to trimethoprim-sulfamethoxazole, particularly cutaneous reactions. Given the importance of this drug for prophylaxis we have attempted to establish a desensitization or tolerance protocol so that patients can continue the drug without repeated adverse reactions.. We studied 34 HIV patients with adverse cutaneous reactions to trimethoprim-sulfamethoxazole, slight to moderate in nature but not life-threatening. Skin tests (prick and intradermal) were done in an attempt to rule out a mechanism of hypersensitivity. Subsequently, trimethoprim-sulfamethoxazole was administered orally in increasing doses beginning with trimethoprim, 0.2 mg, and sulfamethoxazole, 1 mg. The same dose was repeated after 12 hours and then doubled every 24 hours until the therapeutic dose was achieved. If adverse reactions appeared we maintained the last dose administered and administered antihistamines until the reactions cleared or improved.. None of the patients had positive skin tests (immediate or delayed). Twenty- seven patients were satisfactorily desensitized. After a follow-up of 3 months, 25 patients were still incident-free on trimethoprim-sulfamethoxazole prophylaxis, and 19 returning for check-ups at 6 months could still tolerate the drug well.. Our data indicate that patients with adverse reactions to trimethoprim-sulfamethoxazole can continue prophylactic treatment after oral desensitization.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Desensitization, Immunologic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Hypersensitivity; Drug Tolerance; Female; Humans; Male; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; HIV; HIV Seropositivity; Humans; Male; Pneumocystis Infections; Rhabdomyolysis; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the efficacy and toxicity of very high doses of glucocorticoids in patients with congenital pure red cell aplasia (Diamond-Blackfan anemia) who did not respond to standard doses of prednisone.. We prospectively treated eight patients with transfusion-dependent Diamond-Blackfan anemia with high intravenous doses of methylprednisolone. All patients had previously not responded to one or more oral courses of prednisone in standard doses and were dependent on erythrocyte transfusions. Every patient initially received methylprednisolone at a dose of 30 mg/kg per day, followed by slow tapering for 4 weeks, but none responded. All patients then received a second treatment course starting at 100 mg of methylprednisolone per kilogram per day, again followed by slow tapering of the dosage.. Three patients had a complete response that has been sustained for 21+, 31+, and 41+ months, respectively. One patient had a partial response. Toxic effects included a rise in serum alanine aminotransferase activity in all patients, transient diabetes mellitus in one child, and three episodes of bacteremia in two patients with intravenous access devices.. We conclude that very high doses of methylprednisolone may induce sustained remission in some patients with transfusion-dependent Diamond-Blackfan anemia refractory to standard-dose prednisone therapy.

Topics: Adolescent; Age of Onset; Anemia, Refractory; Anti-Infective Agents; Child, Preschool; Clinical Protocols; Dose-Response Relationship, Drug; Fanconi Anemia; Glucocorticoids; Humans; Infant; Methylprednisolone; Pneumocystis; Pneumocystis Infections; Prednisone; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The use of semiquantitative PCR (SQPCR) to assess Pneumocystis carinii pneumonia (PCP) infection and its response to treatment was studied with rats. Groups of eight rats were immunosuppressed with steroids for 3 to 12 weeks. Untreated controls were maintained for the same periods. Three groups of rats were treated with pentamidine, three groups were treated with trimethoprim-sulfamethoxazole, and three groups of rats were tapered from steroids. At various times during suppression, rats from the different groups were sacrificed. At necropsy, lungs were lavaged to obtain bronchoalveolar fluids and then homogenized. Bronchoalveolar fluids and homogenates were assayed by cyst counting and SQPCR. An increase in the SQPCR signal was seen throughout immunosuppression, with a slow decrease upon the withdrawal of steroids and a faster decrease with drug treatment. SQPCR results with lung homogenates and bronchoalveolar fluids strongly correlated with each other and with cyst counts. These results warrant investigation of SQPCR for assessing treatment results of human P. carinii pneumonia infection.

Topics: Animals; Base Sequence; Bronchoalveolar Lavage Fluid; DNA, Fungal; Immunosuppression Therapy; Molecular Sequence Data; Pentamidine; Pneumocystis; Pneumocystis Infections; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; Trimethoprim, Sulfamethoxazole Drug Combination

Several drugs have been shown to have anti-Pneumocystis carinii activity in clinical trials. Because of the large number of patients required, no more than 3 drugs can be compared for efficacy in human studies. However, the experimental animal model for P. carinii pneumonitis is remarkably similar to the human disease and was used to compare 10 drugs for the relative potency against this infection. All drugs were compared at doses known to prevent the pneumonitis in > 80% of animals and at one-tenth of this dose. Drugs effective at the lowest dose were further tested at one-hundredth the original doses, and drugs ineffective were retested at 10 and 100 times the original dose. Trimethoprim-sulfamethoxazole was the most effective drug, with azithromycin-sulfamethoxazole and clarithromycin-sulfamethoxazole next most effective. Intravenous pentamidine and clindamycin-primaquine were the least effective. Atovaquone, sulfadoxine-pyrimethamine, erythromycin-sulfisoxazole, PS-15, and dapsone-trimethoprim had intermediate activity.

Topics: Animals; Anti-Infective Agents; Atovaquone; Azithromycin; Clarithromycin; Clindamycin; Clinical Trials as Topic; Dapsone; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Therapy, Combination; Humans; Naphthoquinones; Pentamidine; Pneumocystis Infections; Proguanil; Pyrimethamine; Rats; Sulfadoxine; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Prophylactic efficacy of antimicrobial agents against pneumocystosis and toxoplasmosis was examined in a model of concurrent Pneumocystis carinii and Toxoplasma gondii infections in rats. Corticosteroid-treated rats naturally infected by P. carinii were challenged with the RH strain of T. gondii. Infection was assessed by counting P. carinii cysts in lung and by titration of T. gondii in tissues by tissue culture. Untreated rats died after challenge, with P. carinii infection in lungs and T. gondii infection in liver, spleen, lungs, and brain. In rats that received trimethoprim-sulfamethoxazole or pyrimethamine plus dapsone, T. gondii was eradicated and P. carinii pneumonia prevented. Roxithromycin, 200 or 400 mg/kg, provided significant protection against toxoplasmosis but had no efficacy against P. carinii. Atovaquone, 100 or 200 mg/kg, had only partial efficacy against pneumocystosis and toxoplasmosis. These results definitively confirm use of trimethoprim-sulfamethoxazole and pyrimethamine plus dapsone for prophylaxis against combined infection in immunocompromised hosts.

Topics: Animals; Antifungal Agents; Antiprotozoal Agents; Atovaquone; Brain; Dapsone; Drug Therapy, Combination; Liver; Lung; Male; Mice; Naphthoquinones; Pneumocystis; Pneumocystis Infections; Pyrimethamine; Rats; Rats, Wistar; Roxithromycin; Spleen; Toxoplasma; Toxoplasmosis, Animal; Trimethoprim, Sulfamethoxazole Drug Combination

A series of 2,4-diamino-5-methyl-6-(anilinomethyl)pyrido[2,3-d]pyrimidines 4-9 were synthesized as 5-deaza nonclassical antifolates containing trimethoxy, dichloro-, or trichlorophenyl substitutions and a N-H, N-CH3, or N-CHO at the 10-position. The compounds were evaluated as inhibitors of dihydrofolate reductases (DHFR) from Pneumocystis carinii (P. carinii), Toxoplasma gondii (T. gondii), rat liver (RL), and Lactobacillus casei (L. casei); as inhibitors of T. gondii and P. carinii cell growth in culture; and as antitumor agents. The compounds were prepared by modifications of procedures for classical 5-deaza folates. 2,4-Diamino-5-methyl-6-[(3',4',5'-trimethoxy-N- methylanilino)methyl]pyrido[2,3-d]pyrimidine (5a) exhibited high potency as well as selectivity (compared to RL DHFR) for P. carinii and T. gondii DHFR. Compound 5a is one of the most potent and selective nonclassical folate inhibitors of T. gondii DHFR known. The N-10 formyl analogue 2,4-diamino-5-methyl-6-[(N-formyl-3',4',5'-trimethoxyanilino) methyl]pyrido-[2,3-d]pyrimidine (6a) had decreased potency, but it maintained high selectivity for T. gondii DHFR. The corresponding chloro-substituted analogues maintained potency or had decreased potency; N-10 substitution did not increase potency or selectivity to the extent observed in the 3',4',5'-trimethoxy series. Partial reduction of the B ring to afford the dihydro analogue 2,4-diamino-5-methyl-6-[(N-formyl-3',4',5'-trimethoxyanilino) methyl]-5,8-dihydropyrido[2,3-d]pyrimidine (7), its 5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine analogue 8, and 2,4-diamino-5-methyl-6-[(3',4',5'-trimethoxyanilino)methyl]-5,6,7, 8- tetrahydropyrido[2,3-d]pyrimidine (9) resulted in a significant decrease in potency. In T. gondii cell culture inhibitory studies, 2,4-diamino-5-methyl-6-[(3',4',5'- trimethoxyanilino)methyl]pyrido[2,3-d]pyrimidine (4a), 5a, and 6a were less potent compared to their DHFR inhibitory potencies. Against P. carinii cells in culture, 4a and 5a at 10 micrograms/mL were as effective as the clinically used combination of trimethoprim/sulfamethoxazole (50/250 micrograms/mL). With the exception of the B ring reduced analogues 7-9, all of the compounds were significantly cytotoxic to leukemia CCRF-CEM cells in culture. The chloro-substituted analogues, in general, were more potent against a variety of other tumor cells in culture than the trimethoxy analogues. These results were corroborated by the preclinical tumor screening program at the Natio

Topics: Animals; Antineoplastic Agents; Disease Models, Animal; Folic Acid Antagonists; Fungal Proteins; Humans; Liver; Mice; Molecular Conformation; Neoplasms, Experimental; Oxidation-Reduction; Pneumocystis; Pneumocystis Infections; Protozoan Proteins; Pyrimidines; Rats; Structure-Activity Relationship; Toxoplasma

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Choroiditis; Eye Infections, Fungal; Humans; Male; Pentamidine; Pneumocystis Infections; Premedication; 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

The sesquiterpene bilobalide, extracted from Ginkgo biloba leaves, was tested in vitro and in vivo for the ability to inhibit Pneumocystis carinii growth. Bilobalide was inhibitory to trophozoites cultured on human embryonic lung fibroblasts (HEL 299) at approximately the same concentration as trimethoprim plus sulfamethoxazole (lowest effective concentration, 50 micrograms of bilobalide per ml versus 9/45 microgram of trimethoprim-sulfamethoxazole per ml), inducing microscopically detectable morphological changes in the cytoplasm of the parasite. In pharmacologically immunosuppressed Sprague-Dawley rats transtracheally infected with a suspension of about 5 x 10(6) P. carinii trophozoites per ml, the daily intraperitoneal administration of bilobalide (10 mg/kg of body weight for 8 days) lowered the number of organisms by approximately 2 logs (that is, about 99%). There was no apparent toxicity either in uninfected HEL 299 feeder cells or in infected and uninfected animals. These studies suggest that the sesquiterpene bilobalide might be useful for therapy of and prophylaxis against P. carinii infections in humans.

Topics: Acetone; Animals; Cells, Cultured; Cyclopentanes; Diterpenes; Female; Fibroblasts; Furans; Ginkgolides; Humans; Plant Extracts; Plants, Medicinal; Pneumocystis; Pneumocystis Infections; Rats; Rats, Sprague-Dawley; Trimethoprim, Sulfamethoxazole Drug Combination

This study was undertaken to determine whether patients infected with HIV and with prior hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) can be rechallenged successfully with TMP-SMX, what factors predict successful rechallenge, and whether hypersensitivity is due to TMP or to SMX.. A prospective, open study.. A tertiary referral hospital.. Thirty-one HIV-infected patients with a history of non-life-threatening hypersensitivity to TMP-SMX.. Patients received TMP (300 mg twice a week) for 2 weeks and, where no major reaction occurred, subsequently with TMP-SMX (160 and 800 mg per tablet, one tablet two times a day, twice a week). Patients who developed significant and persistent hypersensitivity ceased SMX and were subsequently challenged with TMP-dapsone (300 and 100 mg, respectively, twice a week).. That rechallenge is more likely to be successful in those with advanced HIV disease.. Five out of 31 (16%) patients developed hypersensitivity to TMP, and two ceased TMP as a result. Fifteen of the 26 (58%) patients who received subsequent TMP-SMX developed hypersensitivity, 12 of whom ceased TMP-SMX because of this reaction. Hypersensitivity to TMP-SMX was significantly less common in those with a CD4+ cell count < 20 x 10(6)/l than in those with a CD4+ cell count > 20 x 10(6)/l (31 versus 85%; P = 0.03). Hypersensitivity to TMP-dapsone occurred in two out of nine patients with hypersensitivity to TMP-SMX on rechallenge. One patient developed transient dyspnoea following a dose of SMX, but no other serious adverse drug reaction occurred.. Rechallenge with TMP-SMX appears safe in HIV-infected patients with a history of non-life-threatening hypersensitivity and is most likely to be successful in patients with a low CD4+ lymphocyte count. The data suggest a low rate cross-hypersensitivity between SMX and dapsone, at least at the doses used.

Topics: Adult; AIDS-Related Opportunistic Infections; Cross Reactions; Drug Eruptions; Drug Hypersensitivity; HIV Infections; Humans; Male; Pneumocystis Infections; Safety; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Cohort Studies; Heart Transplantation; Humans; Pneumocystis Infections; Time Factors; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

A transtracheally inoculated mouse model of Pneumocystis carinii has been developed using BALB/c mice. The advantage of this strain of mice include that they are widely available, inexpensive, and were not infected with Pneumocystis before inoculation. Inoculated mice that were not treated had a mean infectivity score of 4.1 compared with inoculated mice treated with the effective anti-Pneumocystis drug combination of trimethoprim plus sulfamethoxazole, which had a mean infectivity score of 0.1, an approximately 4 log difference. The inoculated BALB/c mouse provides a model to serve as a valuable addition to rat models currently used, providing a source of organisms from a different host for cross-species comparisons and for studies of drug efficacy for therapy and prophylaxis. The inoculated mouse is especially cost effective and allows testing of compounds in short supply.

Topics: Aminoquinolines; Animals; Antimalarials; Clindamycin; Dexamethasone; Disease Models, Animal; Drug Therapy, Combination; Immunosuppression Therapy; Mice; Mice, Inbred BALB C; Pneumocystis Infections; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Contraindications; Humans; Nursing, Practical; Opportunistic Infections; Pentamidine; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Extrapulmonary Pneumocystis carinii infections in AIDS are still rare although the number of cases is increasing. We present 2 cases of extrapulmonary pneumocystosis detected at our institution during an 8-month period. The first was a patient treated for P. carinii pneumonia (PCP) disseminated to liver, spleen and kidneys. The second patient had widely dissemination of P. carinii diagnosed at autopsy. Both patients had received aerosolised pentamidine (AP) for PCP prophylaxis. Totally we have treated patients with AP prophylaxis for 122 patient years and found a frequency of extrapulmonary spread of 1.6% compared to none in the 116 patient years on sulfamethoxazole-trimethoprim.

Topics: Acquired Immunodeficiency Syndrome; Aerosols; Humans; Kidney; Liver; Lung; Male; Middle Aged; Pentamidine; Pneumocystis; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination