Efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of pneumocystis pneumonia in human immunodeficiency virus-negative immunodeficient patients: A systematic review and meta-analysis

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Fig 1. Flow diagram of studies included in the meta-analysis.

PRISMA flow diagram showing the number of articles identified and evaluated during the review.

Fig 2. Forest plot of the incidence rate of PCP incidence.

The vertical line indicates no difference between the groups. ORs are represented by diamonds, and 95% CIs are depicted by horizontal lines. Squares indicate point estimates, and the size of each square indicates the weight of the given study in the meta-analysis. M-H, Mantel-Haenszel random-effects model.

Fig 3. Forest plot of the rate of drug discontinuation.

The vertical line indicates no difference between the groups. ORs are represented by diamonds, and 95% CIs are depicted by horizontal lines. Squares indicate point estimates, and the size of each square indicates the weight of the given study in the meta-analysis. M-H, Mantel-Haenszel random-effects model.

Fig 4. Forest plot of the rate of mortality.

The vertical line indicates no difference between the groups. ORs are represented by diamonds, and 95% CIs are depicted by horizontal lines. Squares indicate point estimates, and the size of each square indicates the weight of the given study in the meta-analysis. M-H, Mantel-Haenszel fixed-effects model.

Fig 5. Forest plot of the rate of AEs.

The vertical line indicates no difference between the groups. ORs are represented by diamonds, and 95% CIs are depicted by horizontal lines. Squares indicate point estimates, and the size of each square indicates the weight of the given study in the meta-analysis. M-H, Mantel-Haenszel random- effects model.