*Purpose: Invasive fungal infection (IFI) after liver transplant (LTx) is associated with increased morbidity and mortality. Studies show that IFI prophylaxis improves outcomes but the prophylaxis regimen and patient selection criteria are not well established. The objective of this study was to evaluate the impact of our fungal prophylaxis protocol (FPP) on liver transplant outcomes.

*Methods: We performed a single center, retrospective study of adult LTx recipients between 7/1/09-6/30/17. We initiated our FPP on 9/1/16 in patients with one of the following criteria: liver re-transplantation, pre-transplant dialysis, pre-transplant hospitalization > 7 d, pre-transplant candidal colonization, MELD > 35, OR time > 10 h, biliary-enteric anastomosis, intraoperative transfusion requirement of ≥40 units cellular blood products, and return to OR within 30 d. Patients meeting criteria were given 400 mg of fluconazole on POD 1-14. For this analysis patients were divided into two groups; those screened for inclusion in our FPP between 9/1/2016-6/30/17 and a pre-implementation historical control group (7/1/2009-6/30/2013)

*Results: 189 patients met inclusion criteria; 50 in the FPP group, and 139 in the control group. Patient demographics were similar between groups with the exception of higher MELD, more donation after circulatory death (DCD) and live liver donors and increased thymoglobulin use in the FPP group. There were significantly fewer fungal infections in the FPP group at 1 year (12% vs 27%, p=0.03). IFI occurred in the first 3 months in approximately 70% of cases, both in the FPP and control groups (FPP: 67% (4/6) and control 75% (30/40)). IFI in the control group was due to Candida species in 95% of cases of which 30% were species with reduced fluconazole susceptibility. IFI in the FPP group was due to Candida species in all cases, and no isolates with expected reduced fluconazole susceptibility. Aspergillus did not account for any IFI between the groups. One-year patient and graft survival were similar between groups. In a multivariable model accounting for patient and donor age, donor type, MELD, and cold ischemic time, FPP was protective against fungal infection (HR 0.3, p=0.015); DCD and living donor status resulted in increased IFI risk (DCD HR 3.4 p=0.004, Living Donor: HR 7.9 p=0.03). FPP had no impact on graft survival (HR 0.4, p=0.14), but trended toward improved patient survival. (HR 0.18, p=0.06).

*Conclusions: A protocolized approach to IFI prophylaxis utilizing fluconazole after LTx was successful in significantly reducing IFI in a high risk population without a shift in yeast resistance patterns. Further streamlining of inclusion/exclusion and investigation of immunosuppressive augmentation is necessary.

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