A targeted fungal prophylaxis protocol with static dosed fluconazole significantly reduces invasive fungal infection after liver transplantation

摘要

Abstract Background Invasive fungal infection (IFI) after liver transplant (LTx) is associated with extensive morbidity and mortality. Targeted prophylaxis reduces risk, but qualifying criteria, drug of choice and regimen are unclear and compliance is inconsistent. Objective Assess the impact of a risk factor‐based fungal prophylaxis protocol (FPP) after LTx on fungal infection rates, fungal epidemiology, and transplant outcomes. Methods Observational cohort study of adult LTx recipients between July 1, 2009, and June 30, 2017. Patients in the FPP group were given a set dose of 400?mg fluconazole without renal adjustment on POD 1‐14 via pharmacist delegation protocol. Results One hundred and eighty‐nine patients met inclusion criteria; 50 in the FPP and 139 in the pre‐implementation comparator group. Of those who would be considered high‐risk, 22.3% received antifungal prophylaxis prior to FPP implementation vs 92% after implementation ( P ??.0001). There were significantly fewer fungal infections in the FPP group at 1?year (12.5% vs 26.6%, P ?=?.03). IFI in the pre‐implementation control group was due to Candida species in 95% of cases; 30% were species with reduced fluconazole susceptibility. IFI in the FPP group was due to Candida species in all cases, and no isolates had 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 ?=?.015). FPP did not significantly impact graft survival (HR 0.4, P ?=?.14), but trended toward improved patient survival. (HR 0.18, P ?=?.06). Conclusion Implementation of a targeted FPP utilizing static dosing of fluconazole 400?mg?×?14?days to those that meet high‐risk criteria significantly reduces invasive fungal infection after liver transplant. Use of this protocol did not adversely affect fungal epidemiology and may have a positive impact on allograft and patient survival. Future large prospective studies are needed to better evaluate survival impact.