Prophylaxis of Pneumocystis Pneumonia in Immunocompromised Non-HIV-Infected Patients: Systematic Review and Meta-analysis of Randomized Controlled Trials

• Published in: Mayo Clinic proceedings Vol. 82; no. 9; pp. 1052 - 1059
• Main Authors: Green, Hefziba, Paul, Mical, Vidal, Liat, Leibovici, Leonard
• Format: Journal Article
• Language: English
• Published: Rochester, MN Elsevier Inc 01.09.2007; Mayo Medical Ventures; Elsevier, Inc; Elsevier Limited
• Subjects: Anti-Infective Agents - administration & dosage; Anti-Infective Agents - therapeutic use; Antibiotic Prophylaxis; Biological and medical sciences; Care and treatment; General aspects; Humans; Immunocompromised Host; Internal Medicine; Medical sciences; Pneumocystis carinii; Pneumocystis carinii pneumonia; Pneumonia, Pneumocystis - mortality; Pneumonia, Pneumocystis - prevention & control; Prevention; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; Randomized Controlled Trials as Topic; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination - administration & dosage; Trimethoprim, Sulfamethoxazole Drug Combination - therapeutic use; United States; RR; CER; HIV; NNT; TMP-SMX; CI; MeSH; NNH; PCP; relative risk; medical subject headings; Pneumocystis pneumonia; control event rate; number needed to harm; trimethoprim-sulfamethoxazole; human immunodeficiency virus; confidence interval; number needed to treat; Immunopathology; Lung disease; Pneumonia; Respiratory disease; Systematic review; AIDS; Immune deficiency; Evidence-based medicine; Metaanalysis; Fungi; Infection; Prevention; Randomization; Viral disease; Randomised controlled trial; Clinical trial; Pneumocystis; Fungi Imperfecti; Bibliographic review; Thallophyta
• ISSN: 0025-6196; 1942-5546
• DOI: 10.4065/82.9.1052

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.