Targeted peri-operative prophylaxis in patients colonized with Carbapenem Resistant Enterobacterales undergoing Liver Transplantation: a multinational cohort study

Background: Targeted perioperative prophylaxis (T-PAP) has been proposed to mitigate the impact of Carbapenem-Resistant Enterobacterales (CRE) infections in patients colonized with CRE who are undergoing liver transplantation (LT). This study aims to investigate the impact of T-PAP versus standard perioperative prophylaxis (S-PAP) in preventing CRE infections. Methods: Observational, multinational cohort study of adults with CRE colonization at LT. The endpoints were CRE infection within 15 and 30 days after LT. Exposure was T-PAP defined as the use of agents with in vitro activity against the colonizing strain. T-PAP was differentiated into T-PAP with old drugs (T-PAPold) and T-PAP with novel drugs (T-PAPnew) according to the regimens used. T-PAPnew included patients exposed to new betalactam/betalactamse inhibitors (BL/BLIs) or cefiderocol. Treatment-effect models with augmented inverse probability weighting were employed to assess the average treatment effect (ATE) of T-PAPold and T-PAPnew versus S-PAP on CRE infection. Results: A total of 408 CRE pre-transplant carriers were included. T-PAPold was administered to 112 patients (27.5%), and T-PAPnew was administered to 28 patients (6.9%). Post-transplant CRE infection at 15 and 30 days occurred in 87 (21.4%) and 106 (26.0%) patients, respectively. The ATE of T-PAPnew at 15 and 30 days post-transplant was -0.146 (p=0.002) and -0.056 (p=0.320), respectively. The ATE of TPAPold at 15 and 30 days post-transplant was 0.003 (p=0.941) and -0.005 (p=0.897) respectively. Conclusions: The protective effect of T-PAPnew in preventing CRE infections is significant within the first 15 days, but its effectiveness decreases within the first month. [CRECOOLT Study Group]