Low-versus conventional-dose trimethoprim-sulfamethoxazole for non-HIV PCP

Abstract

Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP); however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited. We aimed to evaluate the efficacy and safety of low-dose TMP-SMX after adjusting for patient background characteristics. In this multicentre retrospective cohort study, we included patients diagnosed with non-human immunodeficiency virus (HIV) PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low- (TMP equivalent <12.5 mg/kg) and conventional-dose groups (TMP equivalent 12.5-20 mg/kg/day). The primary endpoint was 30-day mortality, and the secondary endpoints were 180-day mortality, adverse events of grade 3 or greater per the Common Terminology Criteria for Adverse Events Version 5.0, and initial treatment completion rates. The background characteristics were adjusted using the overlap weighting method with propensity scores. Fifty-five patients in the low-dose and 81 in the conventional-dose groups were evaluated. There was no significant difference in 30-day mortality (7.6% vs. 14.9%, P = 0.215) or 180-day mortality (18.1% vs. 24.0%, P = 0.416) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (27.3% vs. 58.6%, P = 0.001). The initial treatment completion rates were 43.8% and 27.7% in the low-dose and conventional-dose groups, respectively. Low-dose TMP-SMX did not alter survival but reduced the incidence of adverse events in patients with non-HIV PCP, compared with conventional-dose TMP-SMX.