Post-orthotopic liver transplantation (OLT) infections, especially multidrug resistant organisms (MDRO), are implicated in poorer outcomes, fueling efforts to elucidate risk factors for hospital acquired infections. However, few studies address effects of pre-OLT antibiotics or post-OLT immunosuppression (IS) on ICU infections (non-MDRO and MDRO). We hypothesized that excess non-prophylactic pre-OLT antibiotics and poor IS titration worsened morbidity and graft survival in OLT.

A single-center retrospective review of liver and combined liver-kidney transplants (127 males, 60 females) was conducted (2013-2015). Data abstracted from the registry included patient demographics, lab data, antibiotic data (including infectious data on transfer), culture data, and IS levels. Patients were stratified by pre-OLT MELD (Model for End-Stage Liver Disease) scores using Cochran-Mantel-Haenszel testing. Outcomes were hospital (HLOS) and ICU lengths of stay (LOS) and graft survival. Infections were defined by Centers for Disease Control guidelines. Therapeutic cutoffs for tacrolimus troughs were 5-20 ng/ml and 100-350 ng/ml for cyclosporine. Data was analyzed by Chi-Square and unpaired Student's t-test with p<0.05 denoting statistical significance. Kaplan-Meier survival curves with log-rank tests and hazard ratios were reported for 1-year mortality.

There was no significant heterogeneity between MELD stratified groups ([Chi]²_MH=0.32, p<0.57). Pre-OLT risk factors for infections included outside hospital transfer ([Chi]²=7.83, p=0.005, non-MDRO; [Chi]²=5.24, p=0.022, MDRO), excess antibiotic use ([Chi]²=8.8, p=0.003, non-MDRO; [Chi]²=6.42, p=0.011, MDRO), and non-therapeutic IS levels after 7 days ([Chi]²=8.66, p=0.003, non-MDRO; [Chi]²=16, p<0.001, MDRO). Excess antibiotics increased mean HLOS (43±24.1 vs 25.8±28.5d, p<0.001) and ICU LOS (23.7±16.4 vs 11.2±14.8d, p<0.001), and worsened one-year mortality (22.6 vs 8.8%), hazard ratio 0.41, 95% CI [0.18, 0.94].

These data suggest excess antibiotics pre-OLT and poor IS titration post-OLT increase development of ICU infections, lengthen HLOS and ICU LOS and worsen 1-year mortality and survival. Targeted efforts should be made to restrict pre-OLT antibiotics in the ICU.

CITATION INFORMATION: Yee J, Clark D, Hogen R, Dhanireddy K, Biswas S, Cobb J, Matsushima K, Grabo D, Strumwasser A. Antibiotic Conservatorship in Orthotopic Liver Transplantation. Am J Transplant. 2017;17 (suppl 3).

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