trimethoprim--sulfamethoxazole-drug-combination and Bone-Marrow-Diseases

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

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

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Bone Marrow Diseases; Diarrhea; Duodenal Diseases; Edema; Enteral Nutrition; Humans; Hypotension; Leg; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acetamides; Aged, 80 and over; Anesthesia; Anti-Bacterial Agents; Bacteremia; Bone Marrow Diseases; Comorbidity; Contraindications; Daptomycin; Drug Administration Schedule; Drug Therapy, Combination; Gentamicins; Hip Prosthesis; Humans; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Systemic Inflammatory Response Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Pancytopenia, although mainly reported in adults, has also been described in children with brucellosis. However, bone marrow hypoplasia is a rare feature of the infection. An 11-year-old boy was admitted with fever, vomiting, and abdominal pain of 10 days' duration. On physical examination, pallor and high fever were detected in the absence of lymphadenopathy and hepatosplenomegaly. His hemoglobin was 8.6 g/dL, white blood cell count 1,100/mm(3), neutrophil count 500/mm(3), platelets 56,000/mm(3), and reticulocytes 0.1%. Hypocellular bone marrow was found by aspiration, and bone marrow biopsy revealed hypocellularity. The agglutination titer was greater than 1/640. Trimethoprim/sulfamethoxazole was prescribed. His fever subsided and pancytopenia subsequently improved. Pancytopenia associated with brucellosis is attributed to hypersplenism, hemophagocytosis, and granulomatous lesions of the bone marrow, which is usually hypercellular. Bone marrow hypoplasia is rarely reported and should be kept in mind in the etiology of aplastic anemia in a country where brucellosis is frequently encountered.

Topics: Agglutination Tests; Anti-Bacterial Agents; Blood Cell Count; Bone Marrow; Bone Marrow Diseases; Brucella; Brucellosis; Child; Humans; Male; Pancytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

A 61-year-old patient with rheumatoid arthritis receiving treatment with methotrexate developed bone marrow hypoplasia after treatment with trimethoprim-sulfamethoxazole. The bone marrow recovered after stopping methotrexate.

Topics: Arthritis, Rheumatoid; Bone Marrow Diseases; Drug Combinations; Drug Interactions; Female; Humans; Methotrexate; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination