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

Pediatr Transplant. 2024 May;28(3):e14740. doi: 10.1111/petr.14740.

Abstract

Background: Pediatric 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.

Methods: This 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.

Results: Forty-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).

Conclusions: An 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.

Keywords: amphotericin B; fungal prophylaxis; hepatotoxicity; lung transplant; micafungin; pediatric; voriconazole.

MeSH terms

  • Adolescent
  • Amphotericin B / therapeutic use
  • Antifungal Agents* / therapeutic use
  • Bilirubin
  • Chemical and Drug Induced Liver Injury*
  • Child
  • Child, Preschool
  • Humans
  • Infant
  • Infant, Newborn
  • Lung
  • Micafungin / therapeutic use
  • Prospective Studies
  • Transplant Recipients
  • Voriconazole / therapeutic use

Substances

  • Antifungal Agents
  • Amphotericin B
  • Voriconazole
  • Micafungin
  • Bilirubin