Efficacy and Safety of Low-Dose Trimethoprim-Sulfamethoxazole (TMP-SMZ) for the Prevention of Pneumocystis jirovecii pneumonia (PJP) in Non-HIV, Non-Transplant Immunosuppressed Patients: A Real-World Cohort Study.

Purpose: To evaluate the noninferiority and safety of low-dose trimethoprim-sulfamethoxazole (TMP-SMZ, 200/40 mg qd) with respect to conventional-dose TMP-SMZ in preventing Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV), non-transplant, immunosuppressed patients. Methods: This retrospective cohort study included patients who received PJP-preventing therapy at the First Affiliated Hospital of Zhejiang University School of Medicine from April 2021 to December 2023. The patients were divided into low-dose group (TMP-SMZ 200/40 mg qd, n=57) and conventional-dose group (400/80 mg qd, n=65). The primary endpoint was the 90-day incidence of PJP, and the secondary endpoints included all-cause mortality and adverse drug events (assessed on the basis of the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 and Kidney Disease: Improving Global Outcomes (KDIGO) criteria). Results: No patients in either group developed PJP within 90 days (risk difference (RD) = 0, 95% confidence interval (CI): -0.05 to 0.05). There was no statistically significant difference in the incidence of adverse reactions (ARs), such as hematologic toxicity (granulocytopenia: 5.26% vs 1.54%, p=0.339), liver injury, and kidney injury, between the low-dose group and the conventional-dose group. The median survival time was 193 days in the low-dose group vs 130 days in the conventional-dose group (p=0.312). Conclusion: In non-HIV, non-transplant, immunosuppressed patients, the efficacy of low-dose TMP-SMZ (200/40 mg/d) in the prevention of PJP was not inferior to that of conventional-dose TMP-SMZ, and the safety profiles of the two doses were equivalent.