Failure of voriconazole therapy due to acquired azole resistance in Aspergillus fumigatus in a kidney transplant recipient with chronic necrotizing aspergillosis

Am J Transplant. 2018 Sep;18(9):2352-2355. doi: 10.1111/ajt.14940. Epub 2018 Jul 12.

Abstract

Invasive aspergillosis (IA) affects the lungs and disseminates mostly in patients with neutropenia and/or patients who are receiving immunosuppressive and steroid therapies. Despite progress in the diagnosis of and therapy for IA, it is still characterized by a high mortality rate. Currently, voriconazole is considered as the standard therapy for IA. Over recent years, triazole-resistant Aspergillus fumigatus isolates have emerged in the environment due to the use of fungicidal agricultural products, with the risk of developing IA related to a resistant isolate. However, resistance may also develop in patients who are undergoing long-term triazole therapy, particularly in the setting of chronic forms of pulmonary aspergillosis. Herein we describe a kidney transplant recipient who failed to respond to voriconazole therapy due to acquired resistance secondary to the appearance of a de novo mutation (Y121F) in the cyp51A gene during chronic necrotizing pulmonary aspergillosis. The infecting isolate acquired voriconazole resistance in 8 months despite plasma concentrations within the recommended range of the drug, necessitating lobectomy in association with a new antifungal strategy consisting of liposomal amphotericin and caspofungin with a good outcome over 36 months.

Keywords: antibiotic: antifungal; clinical research/practice; infection and infectious agents - fungal; infectious disease.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Amphotericin B / therapeutic use
  • Antifungal Agents / therapeutic use*
  • Aspergillus fumigatus / drug effects*
  • Caspofungin / therapeutic use
  • Cytochrome P-450 Enzyme System / genetics
  • Drug Resistance, Fungal / drug effects*
  • Fungal Proteins / genetics
  • Humans
  • Invasive Pulmonary Aspergillosis / drug therapy*
  • Invasive Pulmonary Aspergillosis / etiology
  • Invasive Pulmonary Aspergillosis / pathology
  • Kidney Transplantation / adverse effects*
  • Male
  • Mutation
  • Prognosis
  • Voriconazole / pharmacology*

Substances

  • Antifungal Agents
  • Fungal Proteins
  • liposomal amphotericin B
  • Amphotericin B
  • Cytochrome P-450 Enzyme System
  • cytochrome P-450 CYP51A, Aspergillus
  • Caspofungin
  • Voriconazole