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

  • Hefziba Green
    Affiliations
    Department of Internal Medicine, E Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel
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  • Mical Paul
    Correspondence
    Individual reprints of this article are not available. Address correspondence to Mical Paul, MD, Unit of Infectious Diseases, Rabin Medical Centre, Beilison Hospital, Petah-Tikva, 49100 Israel
    Affiliations
    Department of Internal Medicine, E Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
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  • Liat Vidal
    Affiliations
    Department of Internal Medicine, E Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
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  • Leonard Leibovici
    Affiliations
    Department of Internal Medicine, E Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
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      OBJECTIVE

      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.

      METHODS

      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.

      RESULTS

      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.

      CONCLUSIONS

      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.
      CER (control event rate), CI (confidence interval), HIV (human immunodeficiency virus), MeSH (medical subject headings), NNH (number needed to harm), NNT (number needed to treat), PCP (Pneumocystis pneumonia), RR (relative risk), TMP-SMX (trimethoprim-sulfamethoxazole)
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