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

Dakui Cao,1 Juanfen Mo,2 Haiqin Wang,1 Jianping Jiang,1 Mengqing Cao,1 Ziyi Zhu,1 Hua Zhou3 1Department of Respiratory and Critical Care Medicine, The Second Hospital of Jiaxing, Jiaxing, Zhejiang Province, 314000, People’s Republic of China; 2Central Laboratory, The Second Hospital of Jiaxing, Jiaxing, Zhejiang Province, 314000, People’s Republic of China; 3Department of Respiratory Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, People’s Republic of ChinaCorrespondence: Hua Zhou, Department of Respiratory Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, People’s Republic of China, Email [email protected]: 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.Keywords: trimethoprim-sulfamethoxazole, Pneumocystis jirovecii pneumonia, immunosuppression