A novel approach to reducing hepatotoxicity related to fungal prophylaxis in pediatric lung transplant recipients

Abstract

BackgroundPediatric lung transplant patients are at risk for developing invasive fungal infections post‐transplant. No consensus exists on optimal antifungal regimens and voriconazole, a common first‐line agent, has been shown to cause hepatotoxicity. We describe a single‐center experience utilizing a novel antifungal regimen of intravenous micafungin and nebulized amphotericin B immediately post‐transplant with conversion to an azole at the time of hospital discharge and compare it to a historical cohort of patients who received voriconazole monotherapy throughout their immediate post‐operative course.MethodsThis is a retrospective review of patients in the age 0–18 who received a lung transplant from June 2016–May 2021. Data points collected included: demographic data, transplant date and discharge date, Aspergillus colonization, type of lung transplant, hospitalization and level of care information, induction and antifungal medication regimen; AST, ALT, GGT, bilirubin, and direct bilirubin at various timepoints; and respiratory and blood culture results. The two patient groups were compared by assessment of changes in LFTs and culture results.ResultsForty‐two patients were included in the analysis, with 24 patients receiving micafungin and nebulized amphotericin and 18 patients receiving voriconazole. All patients in both groups experienced a post‐operative elevation in at least one transaminase or bilirubin. More patients in the micafungin/amphotericin group had resolution of all abnormal LFTs by 1 month post‐transplant (p = .036). Additionally, patients in the micafungin/amphotericin group experienced faster normalization of their LFTs compared with the voriconazole group (p < .001). Ten patients in the micafungin/amphotericin group and five patients in the voriconazole group were found to have fungal growth on culture post‐transplant, but this difference was not found to be statistically significant (p = .507).ConclusionsAn antifungal regimen of micafungin and nebulized amphotericin B liposomal may be useful at decreasing the duration of elevated liver enzymes in pediatric patients in the immediate post‐lung transplant period when compared with voriconazole monotherapy. Larger prospective studies looking at antifungal regimens in pediatric patients post‐lung transplant are warranted.