trimethoprim--sulfamethoxazole-drug-combination and Immunologic-Deficiency-Syndromes

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

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

Patients with hypogammaglobulinemia are susceptible to recurrent bacterial, viral, fungal, and parasitic infections. The most common clinical manifestation includes recurrent severe infections caused by encapsulated bacteria, in which antibody opsonization is the primary defense mechanism. To our knowledge, this is the first case report of hypogammaglobulinemia in a Ugandan child in Sub-Saharan Africa. The case emphasizes the importance of including hypogammaglobulinemia in the differential diagnosis for children presenting with a history of recurrent infections.. To raise the index of clinical suspicion of hypogammaglobulinemia in an African child and allow for prompt recognition and management of hypogammaglobulinemia.

Topics: Agammaglobulinemia; Anti-Infective Agents; Antibiotic Prophylaxis; Child; Female; Humans; Immunologic Deficiency Syndromes; Male; Recurrence; Respiratory Tract Infections; Treatment Outcome; 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

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

Hypomorphic mutations in nuclear factor kappa B essential modulator (NEMO) cause X-linked ectodermal dysplasia with immunodeficiency (X-ED-ID). Clinical manifestations in boys with X-ED-ID apart from ectodermal dysplasia and immunodeficiency include osteopetrosis, lymphedema, and colitis. Further description of atypical findings in this disorder is needed. Treatment with allogeneic hematopoietic stem cell transplantation (HSCT) is in its infancy, and how or whether non-immune manifestations of defective NEMO function are impacted by HSCT is poorly described. We report an interesting case of a boy with NEMO mutation who had symptoms reminiscent of Omenn's syndrome and small intestinal villous atrophy with features reminiscent of tufting enteropathy. We describe his treatment course as well as reconstitution of immune function and correction of osteopetrosis post-HSCT, and review the cases of allogeneic HSCT reported to date in the literature.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antifungal Agents; Azithromycin; Cyclosporine; Ectodermal Dysplasia; Fluconazole; Hematopoietic Stem Cell Transplantation; Humans; I-kappa B Kinase; Immunoglobulins, Intravenous; Immunologic Deficiency Syndromes; Immunologic Factors; Immunosuppressive Agents; Infant; Male; Methylprednisolone; Transplantation, Homologous; Treatment Outcome; 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

A 56-year-old Chinese woman with previous disseminated mycobacterium avium complex infection and recurrent cervical abscesses from

Topics: Adult; Anti-Bacterial Agents; Autoantibodies; Drug Hypersensitivity Syndrome; Eosinophilia; Exanthema; Female; Humans; Immunologic Deficiency Syndromes; Interferon-gamma; Middle Aged; Mycobacterium Infections, Nontuberculous; Trimethoprim, Sulfamethoxazole Drug Combination

Good's syndrome (GS) is a rare, adult-onset combined B cell and T cell immunodeficiency with an associated thymoma. These patients have an increased risk of bacterial, fungal, viral and opportunistic infections. This report describes a 75-year-old female patient who presented with a full body rash and an anterior mediastinal mass. She underwent a biopsy of her rash and mass, which revealed erythema multiforme and WHO Type A thymoma, respectively. During her hospitalisation, she was also found to have oropharyngeal candidiasis, methicillin-susceptible

Topics: Aged; Anti-Bacterial Agents; Cardiac Rehabilitation; Erythema Multiforme; Fatal Outcome; Female; Fluid Therapy; Humans; Immunocompromised Host; Immunologic Deficiency Syndromes; Pneumonia; Shock, Septic; Staphylococcal Infections; Thymoma; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Biopsy, Needle; Drug Therapy, Combination; Follow-Up Studies; Humans; Immunocompromised Host; Immunologic Deficiency Syndromes; Lung Neoplasms; Magnetic Resonance Imaging; Male; Meropenem; Middle Aged; Myasthenia Gravis; Nocardia; Nocardia Infections; Opportunistic Infections; Radiography, Thoracic; Risk Assessment; Severity of Illness Index; Syndrome; Thienamycins; Thymoma; Thymus Neoplasms; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Immunodeficiency can occur both in patients undergoing radiation therapy, as well as in patients who have had thymectomies. However, few studies have examined the immune recovery of a patient following both procedures. We aim to emphasize the need for assessment and consistent monitoring of patients with thymoma prior to and after combined treatment of thymectomy and radiation, both of which are likely to result in an increased risk for immunodeficiency.. We describe the longitudinal progress of a 59-year-old Asian male who underwent thymectomy followed by radiation therapy and subsequently presented with generalized urticaria. Revelation of a low absolute lymphocyte count (615 cells/mcL) on initial evaluation prompted further analysis of his immunoglobulin levels and antigen response to a polysaccharide pneumococcal vaccine (PneumoVax-23). Although his immunoglobulin levels were unremarkable, he failed to respond to 11 of 12 serotypes of the pneumococcal vaccine. As a result, he was placed on Bactrim® (trimethoprim-sulfamethoxazole) prophylaxis to prevent opportunistic infections, and his CD4+ and CD8+ counts were monitored over the course of 8 years. His lymphocyte counts 87 months after thymectomy and 85 months after radiation therapy were as follows: absolute lymphocyte count 956 cells/mcL, absolute CD3+/CD4+ 164/mm3 (16%) and absolute CD3+/CD8+ 257/mm3 (25%). The patient was able to discontinue Bactrim® (trimethoprim-sulfamethoxazole) prophylaxis after 9 years of treatment.. The lymphocytopenia, low CD4+ count, and failed response to pneumococcal vaccination that presented in our patient are consistent with immunodeficiency. After radiation alone, a recovery of T-lymphocytes is usually observed after approximately 3 weeks. Over the course of 8 years, he has still not made a full recovery according to laboratory markers, which seem to have stabilized at chronically low levels. To prevent serious complications, we suggest that patients who have undergone both thymectomy and radiation therapy be monitored for immunodeficiency. This case report informs the practices of allergists, oncologists, and neurologists in the continuing care of patients with thymoma.

Topics: Anti-Infective Agents; Humans; Immunoglobulins; Immunologic Deficiency Syndromes; Lymphocyte Count; Male; Middle Aged; Thymectomy; Thymoma; Thymus Neoplasms; Trimethoprim, Sulfamethoxazole Drug Combination

Inherited interleukin-1-receptor-associated kinase-4 (IRAK-4) deficiency is a recently described immunodeficiency associated with pyogenic bacterial infections and a poor inflammatory response. Shigella sonnei is generally associated with outbreaks of rectocolitis in developed countries, but systemic illnesses have occasionally been reported. An underlying primary immunodeficiency has not been found in such cases before now.. We report the clinical and immunological features of a patient with IRAK-4 deficiency who has a history of systemic shigellosis in addition to other infections.. The patient has a history of Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa infections during childhood and an episode of S. sonnei septicemia and meningitis at 10 years of age. This patient's history contrasted with that of other individuals infected concurrently by the same organism. Of note, these episodes were not accompanied by acute phase responses in our patient. Subsequently, the patient has had more episodes of staphylococcal disease, but no systemic illnesses. The patient is now 30 years old and has been doing well since prophylactic antibiotic treatment was stopped 4 years ago.. To our knowledge, this is the first report of a case of systemic shigellosis in a person with a primary immunodeficiency, expanding the spectrum of infections associated with IRAK-4 deficiency. Thus, immunity mediated by IRAK-4 seems to be crucial for both the containment of and the inflammatory response to S. sonnei infection in the intestinal mucosa. IRAK-4 deficiency and related disorders should be considered in patients with systemic shigellosis.

Topics: Anti-Bacterial Agents; Child; Dysentery, Bacillary; Female; Gene Expression Regulation; Humans; Immunologic Deficiency Syndromes; Interleukin-1 Receptor-Associated Kinases; Interleukin-10; Interleukin-6; Intracellular Signaling Peptides and Proteins; Meningitis, Bacterial; Protein Serine-Threonine Kinases; Shigella sonnei; 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

Hyperinsulinemic hypoglycemia associated with trimethoprim-sulfamethoxazole (TMP-SMX) has generally been reported in adults who had renal impairment or in patients with AIDS using high dose TMP-SMX. We present a 5 month-old infant with immunodeficiency due to major histocompatibility complex class II expression defect, developing hypoglycemic convulsion on the third day of high dose TMP-SMX administration. High insulin and C-peptide levels were documented at the time of hypoglycemia. To overcome hypoglycemia while TMP-SMX tapered off, diazoxide was administered which resolved hypoglycemia in 2 months.

Topics: Blood Glucose; C-Peptide; Diazoxide; Drug Administration Schedule; Female; Gene Expression; Genes, MHC Class II; Glucose; Histocompatibility Antigens Class II; Hospitalization; Humans; Hyperinsulinism; Hypoglycemia; Immunologic Deficiency Syndromes; Infant; Infusions, Intravenous; Pneumonia; Seizures; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Humans; Immunologic Deficiency Syndromes; Infant; Male; Pneumocystis; Pneumonia, Pneumocystis; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

We describe three patients with Pneumocystis carinii pneumonia as the initial presentation of severe combined immunodeficiency disease. The pneumonia in the first patient was treated successfully with trimethoprim/sulphamethoxazole (Tmp/Smz). The second patient died despite therapy with Tmp/Smz and pentamidine. The third patient failed to respond to therapy with Tmp/Smz and pentamidine. He was subsequently treated with trimetrexate and leucovorin. Treatment with the new folic acid antagonist trimetrexate resulted in complete recovery. The case histories of these children serve to illustrate the clinical symptoms and new therapeutic modalities of P. carinii pneumonia in patients with immunodeficiency disease.

Topics: Humans; Immunologic Deficiency Syndromes; Infant; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antifungal Agents; Drug Combinations; Glucuronates; Humans; Immunologic Deficiency Syndromes; Infant; Infusions, Intravenous; Leucovorin; Male; Pentamidine; Pneumonia, Pneumocystis; Quinazolines; Respiratory Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Topics: Animals; Antibodies, Monoclonal; Immunologic Deficiency Syndromes; Mice; Mice, Mutant Strains; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

From 1982 to 1987, 22 patients with proven Pneumocystis carinii pneumonia were diagnosed at Wellington Hospital. Patients comprised 15 males and 7 females aged 15-76 years and included seven with AIDS, eight with haematological malignancy and seven with renal disease. Two distinct clinical prodromes occurred. In renal patients a classic fulminating pneumonitis developed over 24 to 72 hours. In patients with AIDS a more indolent illness occurred lasting 3 or more weeks and was characterised by fever, dry cough and breathlessness. Haematology patients showed no specific duration of prodrome. At the time of diagnosis all had an abnormal chest radiograph and the arterial PO2 was reduced in all but one case. An invasive diagnostic procedure was performed in all except one case where the diagnosis was made at post mortem. Two patients required a second procedure to establish the diagnosis. Procedures performed included bronchoalveolar lavage [14], open lung biopsy [7] and transbronchial lung biopsy [2]. All patients were treated with high dose cotrimoxazole and 18 survived to leave hospital. A review of the approach to the diagnosis and treatment of Pneumocystis carinii pneumonia is presented.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Drug Combinations; Female; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Kidney Diseases; Leukemia; Male; Middle Aged; Pneumonia, Pneumocystis; Prognosis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Drug Combinations; Drug Hypersensitivity; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Immunologic Deficiency Syndromes; Neoplasms; Reagins; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Clinical features of 49 episodes of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome were compared with those of 39 episodes in patients with other immunosuppressive diseases. At presentation patients with the syndrome were found to have a longer median duration of symptoms (28 days versus 5 days, p = 0.0001), lower mean respiratory rate (23.4 versus 30, p = 0.005), and higher median room air arterial oxygen tension (69 mm Hg versus 52 mm Hg, p = 0.0002). The survival rate from 1979 to 1983 was similar for the two groups (57% and 50% respectively). Patients with the syndrome had a higher incidence of adverse reactions to trimethoprim-sulfamethoxazole (22 of 34 versus 2 of 17, p = 0.0007). Survivors with the syndrome at initial presentation had a significantly lower respiratory rate, and higher room air arterial oxygen tension, lymphocyte count, and serum albumin level compared to nonsurvivors. Pneumocystis carinii pneumonia presents as a more insidious disease process in patients with the syndrome, and drug therapy in these patients is complicated by frequent adverse reactions.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Child; Drug Combinations; Drug Eruptions; Drug Hypersensitivity; Female; Humans; Immunologic Deficiency Syndromes; Leukocyte Count; Leukopenia; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Respiration; Retrospective Studies; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Drug Combinations; Humans; Hypoglycemia; Immunologic Deficiency Syndromes; Male; Pentamidine; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination