Daily single-strength vs. thrice-weekly double-strength trimethoprim/sulfamethoxazole for Pneumocystis jirovecii prophylaxis in kidney transplant recipients: a non-inferiority randomized control trial

Background: Pneumocystis jirovecii pneumonia (PJP) is a significant concern in kidney transplant (KT) recipients, with trimethoprim/sulfamethoxazole (TMP/SMX) as the recommended prophylaxis. However, direct comparisons between daily single-strength (DSS) and thrice-weekly double-strength (TDS) regimens remain limited. This study evaluated the efficacy of DSS versus TDS TMP/SMX for PJP prevention within the first six months post-transplant, along with side effects, renal outcomes, and patient-reported ease of drug consumption. Methods: We conducted a pilot, single-center, open-label, block-randomized (1:1) non-inferiority trial at Ramathibodi Hospital between December 2022 and December 2023. Adult KT recipients were randomized to receive either TMP/SMX 80/400 mg daily (DSS group) or two SS tablets thrice weekly (TDS group). Patients were followed for six months to assess PJP occurrence, adverse effects, and ease of drug administration. Results: Sixty-five KT recipients were enrolled (DSS: 32, TDS: 33), with a median (IQR) age of 46 (15); 58% were male, 80% received deceased donor kidneys, 17% received anti-thymocyte globulin induction, and 95% were CMV-seropositive. No cases of PJP occurred in either group. The DSS group had a non-significant trend toward lower median (IQR) of white blood cell counts compared to the TDS group [6,235 (3,064) vs.7,052 (3,324) cells/mm³, p = 0.23], with no significant differences in hepatotoxicity or renal dysfunction. Drug convenience was reported in 96% of DSS and 100% of TDS recipients (p = 0.60). Conclusion: Both DSS and TDS TMP/SMX regimens showed comparable safety; however, non-inferiority could not be confirmed due to the absence of PJP in the early post-transplant period. Further studies with larger sample sizes are needed to validate the use of TDS as an alternative prophylactic strategy. (TCTR20220720010, 20 July 2022).