Impact of the Duration of Trimethoprim–Sulfamethoxazole Prophylaxis on the Incidence of Infection After Kidney Transplantation: A Target Trial Emulation Study Within the Swiss Transplant Cohort Study (STCS)—The QUID‐PRO‐QUO Study (QUIDney Transplantation and Duration of PROphylaxis With QUO‐Trimoxazole)

ABSTRACT Background Trimethoprim–sulfamethoxazole prophylaxis effectively prevents opportunistic and non‐opportunistic infections in kidney transplantation, but optimal duration remains uncertain. This study investigated whether extending TMP–SMX prophylaxis is associated with lower infection rates. Methods This target trial emulation using observational data from the Swiss Transplant Cohort Study compared short (< 7 months) versus long (≥ 7 months) TMP–SMX prophylaxis. The primary outcome was bacterial infection potentially susceptible to TMP–SMX up to 12‐months post‐transplant. Inverse probability weighting (IPW) adjusted for confounders including age, living donation, lymphocyte counts, use of antithymocyte globulin, acute rejection, CMV infection, and transplant center. All bacterial and opportunistic infections, kidney function, and patient and allograft survival were summarized descriptively. Results A total of 1700 KTRs fulfilled inclusion criteria; 1325 (78%) participants received a short prophylaxis and 375 (22%) received a long prophylaxis. Median TMP–SMX duration was 179 days in the short group and 280 days in the long group. At 12‐month post‐transplant, the primary outcome was observed in 120/1325 (9.1%) in the short group and 43/375 (11.5%) in the long group. IPW analysis estimated an adjusted risk difference of 2.11% (95% CI −0.47% to 5.27%). Center, rejection, and use of ATG were associated with longer TMP–SMX duration, but risk difference was similar before and after weighting. Urinary tract infection was the most common bacterial infection. Opportunistic and overall infection rates, kidney function, and patient and graft survival were similar among groups. Conclusions In this target trial emulation, no differences in bacterial infection rates at 12‐month post‐transplant was observed between short and long TMP–SMX prophylaxis.