Elsevier

Mayo Clinic Proceedings

Volume 82, Issue 9, September 2007, Pages 1052-1059
Mayo Clinic Proceedings

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

https://doi.org/10.4065/82.9.1052Get rights and content

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.

Section snippets

METHODS

We performed a systematic review and meta-analysis of randomized controlled trials that compared any antibiotic with a known effect against P jirovecii, given orally or intravenously, to no treatment, placebo, or antibiotics with no known effect against P jirovecii. We also included studies that compared different regimens of anti-PCP antibiotics, all administered as prophylaxis. Trial inclusion criteria mandated the assessment of PCP infection as an outcome. We included patients with cancer,

RESULTS

Twelve trials, all but 1 conducted from 1974 to 1997, were included (Table 1).16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 One trial that did not specify recruitment dates was published in 1999.26 The trials included adults and children with hematologic malignant tumors and adults who had received solid organ or bone marrow allografts. A total of 1245 patients were randomized, half of whom were children (610 patients in 5 studies). In all trials PCP infections were defined on the basis of

DISCUSSION

Trimethoprim-sulfamethoxazole prophylaxis was highly effective in preventing PCP infection in immunocompromised non-HIV-infected patients, lowering its incidence by 91% (95% CI, 68%-98%). This effect was seen in both children and adults who had hematologic malignant tumors or who had undergone solid organ transplants. Pneumocystis pneumonia-related mortality was reduced by 83% (95% CI, 6%-97%), whereas no significant differences were seen in all-cause mortality. Severe adverse events did not

CONCLUSIONS

Prophylaxis with TMP-SMX significantly reduced PCP infections and PCP-related mortality in immunocompromised non-HIV-infected patients at risk for PCP. Balanced against the risk for severe adverse events, PCP prophylaxis is warranted for adult patients with an expected risk for PCP of 3.5% or more throughout the period of immunodeficiency. Adverse events are infrequent among children, for whom prophylaxis may be considered at lower PCP incidence rates.

Acknowledgments

This article is based on a Cochrane Review; the systematic review has been published in The Cochrane Library issue 3 (www.thecochranelibrary.com). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and The Cochrane Library should be consulted for the most recent version of the review.41 We thank the Cochrane Gynaecological Cancer Group for their helpful review of the protocol for this review.

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    This article is based on a Cochrane Review published in The Cochrane Library 2007 (see end of article for more details).

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