Association of fungal infection and increased mortality in liver transplant recipients

Abstract

Background: Invasive fungal infection is associated with increased morbidity and mortality following orthotopic liver transplantation (OLTx). Understanding the risk factors associated with fungal infection may facilitate identification of high-risk patients and guide appropriate initiation of antifungal therapy.

Objectives: The aim of this study was to determine the incidence of fungal infections, identify the most common fungal pathogens, and determine the risk factors associated with fungal infections and mortality in OLTx recipients.

Methods: Medical records from 96 consecutive OLTx in 90 American veterans (88 males, 2 females; mean age 48 years, range 32 to 67) performed from January 1994 to December 1997 were retrospectively reviewed for fungal infection in the first 120 days after transplantation. Infection was defined by positive cultures from either blood, urine (<105 CFU/mL), cerebrospinal or peritoneal fluid, and/or deep tissue specimens. Superficial fungal infection and asymptomatic colonization were excluded from study. All patients received cyclosporine, azathioprine, and prednisone as maintenance immunosuppressive therapy. Fungal prophylaxis consisted of oral clotrimazole (10 mg) troches, five times per day during the study period.

Results: Thirty-five patients (38%) had documented infection with one or more fungal pathogens, including Candida albicans (25 of 35; 71%), C torulopsis (7 of 35; 20%), C tropicalis (2 of 35; 6%), non-C albicans (2 of 35; 6%), Aspergillus fumigatus (4 of 35; 11%), and Cryptococcus neoformans (1 of 35; 3%). The crude survival for cases with or without fungal infection was 68% and 87%, respectively (P <0.0001). The median intensive care unit stay and overall duration of hospitalization were significantly longer for patients with fungal infection (P <0.01). The mean time interval from transplantation to the development of fungal infection was 15 days (range 4 to 77) with a mean survival time from fungal infection to death of 21 days (range 3 to 64). Fungal infections occurred significantly more often in patients with renal insufficiency (serum creatinine >2.5 mg/dL), biliary/vascular complications, and retransplantation.

Conclusions: Fungal infections were associated with increased morbidity and mortality following OLTx, with Candida albicans being the most common pathogen. Treatment strategies involving antifungal prophylaxis for high-risk patients and earlier initiation of antifungal therapy in cases of presumed infection are warranted.