Antibiotic Exposure and Risk of Allograft Rejection and Survival After Liver Transplant: An Observational Cohort Study From a Tertiary Referral Centre.

Abstract

Introduction: Our goal is to understand whether there is an association between Abx exposure-and the inferred downstream damage to the intestinal microbiome-and the key patient outcomes of overall survival and rejection following liver transplant.

Methods: We conducted a retrospective cohort study of 462 liver transplant recipients treated at a multistate liver transplant (LTx) service during a 7-year period. The association between antibiotic exposure and outcome was tested across models that addressed antibiotic spectrum, duration, and timing relative to transplant. Cox proportional hazard regression was used to evaluate the relationship between antibiotics with survival and rejection.

Results: The observed 1-year survival in this cohort was 95% (95% CI: 93%, 97%), and 20.8% of patients (96/462) experienced rejection at 1 year. In multivariable analyses, exposure to anaerobe-targeting antibiotics for longer than 14 days pretransplant (p = 0.055) or posttransplant (p = 0.040) was significantly associated with reduced 1-year survival. In multivariable analyses, exposure to any anaerobe-targeting Abx posttransplant was significantly associated with an increased risk of rejection (p = 0.001).

Conclusions: Exposure to anaerobic spectrum antibiotics either before or after LTx was associated with poor outcomes during the first year posttransplant and provides an impetus to further characterize the relationship between antibiotic use, microbiota disruption, and cellular immunity in liver transplantation.