145 - the Efficacy and Safety of Low Dose Trimethoprim-sulfamethoxazole for the Treatment of Pneumocystis Pneumonia: A Systematic Review and Meta-analysis

Background: 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 15-20 mg/kg/day of the trimethoprim component. This high-dose regimen is associated with severe adverse reactions that result in patient harm or treatment discontinuation. Studies have suggested similar mortality and an improved adverse effect profile using lower dose ( < 15 mg/kg/day) SMX-TMP. Our objective of this meta-analysis was to evaluate the safety and efficacy of lower dose SMX-TMP for PJP pneumonia.

Methods: We conducted a systematic review and meta-analysis according to PRISMA guidelines. Pubmed and Embase databases were searched from inception to January 15, 2020, for studies in English evaluating low-dose SMX-TMP ( < 15 mg/kg/day) compared with conventional dosing for the treatment of PJP. Additionally, conference proceedings were reviewed to address potential publication bias. Outcomes evaluated in our meta-analysis include survival and adverse reactions. We performed a sensitivity analysis using E-values to determine the robustness of our results.

Results: After excluding studies that did not meet our inclusion criteria, four studies were analyzed for adverse reaction rates and three for mortality rates. 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). Sensitivity analyses using E-Values reflect a confounder with RR 2.2 or greater could explain away the estimate on adverse events leading to no difference while mortality would require RR 5.6 to reflect worse outcomes with low dose.Mortality Forest Plot
Adverse Effects Forest Plot


Conclusion: This meta-analysis shows a significant decrease in adverse reactions and similar mortality rates with lower-dose SMX-TMP compared with conventional dosing. A low-dose SMX-TMP regimen in the treatment of PJP should be considered a viable option with the potential to decrease treatment discontinuation and reduce harm.