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

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. K E Y W O R D Santifungals, fungal infections, hepatic, prophylaxis, transplantation

Fungal Infections in Liver Transplant Recipients

“…Overall, targeted Candida prophylaxis in high-risk recipients is safe and efficacious in decreasing post-transplant IC, and protocols to ensure its appropriate utilization can improve outcomes [ 101 ].…”

Risk Factors of Invasive Fungal Infection in Recipients After Liver Transplantation: A Systematic Review and Meta-Analysis

“…They were conducted in the USA ( 10 , 22 , 25 , 27 ), Australia ( 26 ), China ( 20 ), Japan ( 11 , 19 , 21 ), Korea ( 12 ), Italy ( 23 , 24 ), Spain ( 18 ), and France ( 7 ). A total of seven studies were cohort studies ( 10 , 12 , 18 , 19 , 23 , 25 , 26 ) and seven were case–control studies ( 7 , 11 , 20 – 22 , 24 , 27 ). All the included studies were evaluated as high quality after being assessed by the NOS.…”

The issue of the antifungal drug choice in prophylaxis of invasive fungal infection after liver transplant

“…We read with interest the study by Jorgenson et al 1 Although we do agree that a simplified prophylaxis protocol increases compliance and consequently reduces IFI, we still believe that an approach based on a diversification of risk factors for Candida or mold infection and local epidemiological data would better allow for a tailored prophylaxis using different antifungal drugs with or without anti-mold activity.…”