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Published on: February 14, 2018
Biliary diffusion and antifungal activity of caspofungin and fluconazole in liver transplant recipients: A pilot
Cécile Garnaud1, Thibaut Gelé2, Elodie Gautier-Veyret3
1Univ. Grenoble Alpes, CNRS, UMR 5525, CHU Grenoble Alpes, VetAgroSup, Grenoble INP, TIMC, 38000, Grenoble, France.
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.
Insights
Caspofungin and fluconazole reach the bile in liver transplant patients, but their effectiveness against intra-abdominal candidiasis requires further investigation. Yeast was detected in some patients receiving caspofungin, questioning its efficacy.
Area of Science:
- Transplantation Medicine
- Infectious Diseases
- Pharmacokinetics
Background:
- Invasive candidiasis, particularly intra-abdominal candidiasis (IAC), is a frequent complication post-liver transplantation.
- Antifungal agents like echinocandins and fluconazole are standard for preventing and treating these infections.
- Limited data exist on antifungal drug diffusion into abdominal sites in liver transplant recipients.
Purpose of the Study:
- To assess the biliary penetration and concentration of caspofungin (CAS) and fluconazole (FCZ) in liver transplant recipients.
- To compare achieved biliary concentrations with minimum inhibitory concentrations (MICs) for common IAC pathogens.
Main Methods:
- A pilot study involving liver transplant recipients treated with caspofungin or fluconazole.
- Quantification of caspofungin and fluconazole concentrations in plasma and bile samples.
- Utilized a validated liquid chromatography-mass spectrometry method for drug level determination.
Main Results:
- Biliary concentrations of CAS ranged from 1.6 to 4.4 mg/L (median 1.9 mg/L) and FCZ from 6.4 to 33.4 mg/L (median 17.7 mg/L).
- Achieved concentrations for both antifungals exceeded MICs for prevalent IAC yeast species.
- Yeast was detected in bile from 3 out of 5 patients treated with caspofungin, despite adequate biliary concentrations.
Conclusions:
- Caspofungin and fluconazole demonstrate biliary diffusion in liver transplant recipients.
- The clinical significance of these concentrations in preventing or treating IAC remains uncertain, especially for caspofungin.
- Further research is needed to confirm the therapeutic efficacy of these antifungals at the site of infection.
