The effectiveness and safety of low dose trimethoprim-sulfamethoxazole for the treatment of pneumocystis pneumonia: A systematic review and meta-analysis.

Abstract

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection causing significant morbidity and mortality in immunocompromised patients. The conventional treatment of PJP is sulfamethoxazole-trimethoprim (SMX-TMP) dosed at 15-20mg/kg/day of the trimethoprim component. Several studies have suggested similar mortality outcomes and an improved adverse effect profile using a lower dose (<15mg/kg/day) SMX-TMP regimen. Our objective of this meta-analysis was to evaluate the safety and efficacy of lower dose SMX-TMP for PJP pneumonia. We conducted a systematic review and meta-analysis of the existing literature according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MEDLINE and Embase databases were searched from inception to January 15, 2020, for studies in English evaluating low-dose SMX-TMP (<15mg/kg/day) compared to conventional dosing for the treatment of PJP. Outcomes evaluated in our meta-analysis include survival and adverse reactions. After excluding studies that did not meet our inclusion criteria, four studies were analyzed for adverse reactions and three for mortality. Overall, there was no significant difference in mortality between low-dose and conventional-dose SMX-TMP groups (relative risk [RR]: 0.55, 95% confidence interval [CI], 0.18-1.70). There was a significant decrease in the rate of adverse reactions for the low-dose group compared with the conventional-dose group (RR: 0.70, 95% CI, 0.53-0.91). This meta-analysis shows a significant decrease in adverse reactions and similar mortality rates with lower-dose SMX-TMP compared to conventional dosing. A low-dose SMX-TMP regimen in the treatment of PJP should be considered a viable option as it could potentially decrease treatment discontinuation rates and reduce patient harm.