Invasive Mold Infections (IMI) among Liver Transplant Recipients (LTR): Is It Time to Reconsider the Risk Factors that Determine Antifungal Prophylaxis?

Abstract

Background IMI have high mortality among LTR. Prevention is critical. Data supporting guideline-recommended three-tiered approach to antifungal prophylaxis based on risk for IMI are lacking.Methods Retrospective study of 534 adult LTR at the Cleveland Clinic (CCF) August 2010–December 2014. We analyzed the association between IMI and risk factors: retransplantation, hemodialysis, reoperation, and fulminant hepatic failure. Model of end-stage liver disease (MELD) was evaluated as novel risk factor. We compared the incidence of IMI among three subgroups: no antifungal prophylaxis, prophylaxis against yeast alone, and prophylaxis against yeast and mold.ResultsMean age was 56 ± 11 years. 68% were male (n = 364). The most common underlying diseases were hepatitis C virus (32%), hepatocellular carcinoma (28%), alcoholic cirrhosis (19%), and nonalcoholic steatohepatitis (19%). The overall incidence of IMI was 0.9% (n = 5). The incidence of IMI among LTR with (n = 128) and without (n = 406) risk factors was 0.78 and 0.98%, respectively (see Figure). Table 1 details the risk factors and outcomes by subgroups. Only one patient with IMI had a risk factor for mold (reoperation). The other four had none. Incidence of IMI among LTR who did not receive antifungal prophylaxis was 1 and 0% in those who received yeast or mold prophylaxis. There was no association between MELD and IMI.Table 1.Risk factors and outcomes of 534 adult LTR at CCF, 2010–2014. No prophylaxis N = 410 (%) Prophylaxis against Candida N = 91 (%) Prophylaxis against mold N = 33 (%) Risk factorsRe-transplantation3 (0.7)8 (9)7 (21)Reoperation after transplant35 (9)24 (26)11 (33)Renal replacement therapy28 (7)26 (29)14 (42)Fulminant hepatic failure4 (1)2 (2)0 (0)Mean MELD (±SD)23 (6)29 (7)32 (8)MELD >22179 (44)73 (80)28 (85)MELD >2951 (12)38 (42)20 (61)OutcomesAny invasive fungal infection21 (5)4 (4)1 (3)Invasive mold5 (1)0 (0)0 (0)One-year all-cause mortality34 (8)12 (13)5 (15)Conclusion Risk factors and MELD did not predict IMI. Because risks are used to recommend mold-active prophylaxis, antifungal agent overuse may be a concern. Additional studies are needed to reconsider risk factors so that transplant providers may target antifungal agents appropriately, practice antifungal stewardship and improve outcomes.Disclosures All authors: No reported disclosures.