Intermittent Versus Daily Trimethoprim/Sulfamethoxazole Regimens for Pneumocystis Pneumonia Prophylaxis: A Systematic Review and Meta-analysis

Background In immunocompromised individuals, trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis pneumonia (PCP) prophylaxis has adverse events, and the optimal dosage is unclear. The objective of this study was to assess efficacy and safety of intermittent versus daily TMP/SMX for PCP prophylaxis.Methods This systematic review included randomized controlled trials (RCTs) indexed in the Cochrane Central Register of Controlled Trials, PubMed, Ichushi, or Embase databases, published from database inception to September 2023. The inclusion criteria were adults taking intermittent or daily TMP/SMX for PCP prophylaxis. Risk of bias was assessed using the Cochrane risk-of-bias tool. The primary outcomes were PCP incidence, PCP-related mortality, and adverse events requiring temporary or permanent TMP/SMX discontinuation.Results Four RCTs (N = 2808 patients) were included. PCP incidence did not differ significantly between the intermittent and daily regimen groups (risk ratio [RR], 1.17 [95% confidence interval {CI}, .89-1.53]; certainty: very low). There was no PCP-related mortality in the 3 RCTs reporting its outcome. Compared with the daily regimen group, the intermittent regimen group experienced significantly fewer adverse events requiring temporary or permanent TMP/SMX discontinuation (RR, 0.51 [95% CI, .42-.61]; certainty: low)Conclusions This systematic review and meta-analysis suggests that intermittent TMP/SMX regimens for PCP prophylaxis may be more tolerable than daily regimens and may have similar efficacy. Further RCTs are needed to apply this to current practice. Clinical Trials Registration. PROSPERO (CRD42022359102).Conclusions This systematic review and meta-analysis suggests that intermittent TMP/SMX regimens for PCP prophylaxis may be more tolerable than daily regimens and may have similar efficacy. Further RCTs are needed to apply this to current practice. Clinical Trials Registration. PROSPERO (CRD42022359102). This systematic review and meta-analysis compared intermittent and daily trimethoprim/sulfamethoxazole regimens for Pneumocystis pneumonia prophylaxis.Our study suggests that intermittent administration may reduce adverse events; however, additional randomized controlled trials are needed to apply this to current practice.