Introduction: Low-dose trimethoprim-sulfamethoxazole is a potentially effective treatment for pneumocystis pneumonia (PCP) with fewer adverse events; however, there is limited evidence available to substantiate this.

Objective: To evaluate the effectiveness and safety of low-dose trimethoprim-sulfamethoxazole in non-human immunodeficiency virus (non-HIV) PCP patients.

Methods: Patients diagnosed with non-HIV PCP and treated with trimethoprim-sulfamethoxazole at three institutions between June 2006 and March 2021 were classified into low-dose (trimethoprim, <12.5 mg/kg) and conventional-dose (trimethoprim, 12.5-20 mg/kg) groups. The primary endpoint was 30-day mortality, and secondary endpoints were 180-day mortality, adverse events of grade 3 or higher per the Common Terminology Criteria for Adverse Events v5.0. Patients? background characteristics were adjusted for by using the overlap weighting method with a propensity score.

Results: Fifty-one patients in the low-dose group and 81 in the conventional-dose group were evaluated. After adjustment for patients? background characteristics, there was no significant difference in 30-day mortality (7.6% vs. 15.7%, P = 0.181) and 180-day mortality (17.9% vs. 25.2%, P = 0.33) rates. The incidence of adverse events was significantly lower in the low-dose group (27.4% vs. 56.9%, P = 0.001).

Conclusions: Low-dose trimethoprim-sulfamethoxazole was associated with fewer adverse events and no difference in survival compared with conventional-dose in patients with non-HIV PCP.