Abstract
BackgroundPneumocystis 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.MethodsA 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.ResultsOf 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).ConclusionsTMP-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.
Highlights
Pneumocystis jirovecii was originally believed to be a protozoan
The efficacy analysis results indicated that the Pneumocystis pneumonia (PCP) incidence was lower in the TMP-SMZ group than in the control group (OR = 0.27, 95% confidence interval (CI) (0.10, 0.77), p = 0.01); the rate of drug discontinuation was higher in the TMP-SMZ group than in the control group
PCP has a significant impact on the mortality of immunocompromised patients, especially those with acquired immune deficiency syndrome (AIDS)
Summary
Pneumocystis jirovecii was originally believed to be a protozoan. Stringer later discovered that it is an atypical fungus taxonomically located between Ascomycota and Basidiomycota that is resistant to most antifungal drugs [1]. The incidence of PCP and PCP-related mortality in HIV-positive patients have gradually decreased due to increasingly mature diagnostic technology, enabling an early diagnosis; refined intensive care management; and active prevention and treatment measures [3] Compared to those in HIV-positive patients, the early clinical symptoms of PCP in HIV-negative immunocompromised patients are not obvious, and delayed diagnosis may eventually lead to death due to sudden respiratory failure. 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 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.
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