Biliary diffusion and antifungal activity of caspofungin and fluconazole in liver transplant recipients: A pilot study

Abstract

Invasive candidiasis, including intra-abdominal candidiasis (IAC), is a common complication after liver transplantation. Antifungal drugs such as echinocandins and fluconazole (FCZ) are frequently used to prevent or treat such fungal infections. The diffusion of these antifungals within abdominal body sites has been rarely reported, in particular, in liver transplant recipients. This study aimed to evaluate the biliary diffusion of caspofungin (CAS) and FCZ. CAS and FCZ concentrations were determined in plasma and bile using a validated liquid chromatography-mass spectrometry method. Biliary concentrations of CAS (n = 5) and FCZ (n = 12) ranged from 1.6 to 4.4 and 6.4 to 33.4 mg/L, respectively, with respective medians of 1.9 and 17.7 mg/L. These values are higher than the MICs for yeast species frequently involved in IAC, suggesting that such antifungal exposure is sufficient to prevent/cure these infections. However, yeast was found in bile collected during CAS treatment from 3/5 patients, raising questions about the effective antifungal activity of this echinocandin at this anatomical site. Our pilot study shows that CAS and FCZ diffuse to the bile of liver transplant recipients. However, whether the observed antifungal concentrations are sufficiently high to prevent/cure IAC remains an unanswered question.

Keywords: Bile; Caspofungin; Diffusion; Fluconazole; Liver transplantation.