*Purpose: There is a paucity of data defining the optimal agent and timing of peri-operative antimicrobial prophylaxis in orthotopic liver transplantation (OLT). The purpose of this study was to evaluate the effects of a short duration, narrower spectrum peri-operative antibiotic prophylaxis regimen on multi-drug resistant (MDR) surgical site infection (SSI) rates.

*Methods: This was a single-center, retrospective cohort study comparing 24-hours of ampicillin-sulbactam (post-cohort) to 5-7 days of vancomycin with either cefepime and metronidazole or piperacillin-tazobactam (pre-cohort). The primary outcome was incidence of MDR SSIs. Patients were excluded if there were MDR organism(s) present pre-operatively. Secondary outcomes included rates of surgical site, nosocomial, and fungal infections, as well as hospital and intensive care unit (ICU) length of stay (LOS), antibiotic-free days, and in-hospital, all-cause mortality.

*Results: Baseline characteristics were balanced with the exception of Model for End-Stage Liver Disease (MELD-Na) score (31 vs 20, p = 0.005). There was no difference in MDR SSI between groups. Furthermore, there was no difference in any post-operative infection rates including overall rates of SSI (Table 1) or in-hospital mortality. When evaluated by MELD-Na score, there was still no statistically significant difference between groups. There were significantly more antibiotic-free days in the post-cohort (13.4 vs 18.3 days, p = 0.003). Additionally, there was a significantly shorter ICU and hospital LOS in the post-cohort (20.2 vs 9.3 days, p = 0.009 and 29.7 vs 15.3 days, p = 0.005).

*Conclusions: A peri-operative antibiotic prophylaxis regimen in OLTs consisting of 24-hours of ampicillin-sulbactam compared to a 5-7 day broader antibiotic regimen was not associated with any difference in rates of post-operative infections. It was however, associated with significantly more antibiotic-free days. Also, although this regimen was associated with a significantly shorter ICU and hospital LOS, this was likely confounded by the differences in disease severity between the groups.

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