Surveillance for Azole-Resistant Aspergillus fumigatus in a Centralized Diagnostic Mycology Service, London, United Kingdom, 1998-2017.

Alireza Abdolrasouli,Hugo Donaldson,Hyun Park,Timothy M Rawson,Darius Armstrong-James,Matthew C Fisher,Johanna L Rhodes,Luke S P Moore,Alison H Holmes,Michael A Petrou

doi:10.3389/fmicb.2018.02234

Abstract

Background/Objectives: Aspergillus fumigatus is the leading cause of invasive aspergillosis. Treatment is hindered by the emergence of resistance to triazole antimycotic agents. Here, we present the prevalence of triazole resistance among clinical isolates at a major centralized medical mycology laboratory in London, United Kingdom, in the period 1998–2017.Methods: A large number (n = 1469) of clinical A. fumigatus isolates from unselected clinical specimens were identified and their susceptibility against three triazoles, amphotericin B and three echinocandin agents was carried out. All isolates were identified phenotypically and antifungal susceptibility testing was carried out by using a standard broth microdilution method.Results: Retrospective surveillance (1998–2011) shows 5/1151 (0.43%) isolates were resistant to at least one of the clinically used triazole antifungal agents. Prospective surveillance (2015–2017) shows 7/356 (2.2%) isolates were resistant to at least one triazole antifungals demonstrating an increase in incidence of triazole-resistant A. fumigatus in our laboratory. Among five isolates collected from 2015 to 2017 and available for molecular testing, three harbored TR34/L98H alteration in the cyp51A gene that are associated with the acquisition of resistance in the non-patient environment.Conclusion: These data show that historically low prevalence of azole resistance may be increasing, warranting further surveillance of susceptible patients.

Highlights

Aspergillus fumigatus is a ubiquitous ascomycete mold and the primary etiologic agent of aspergillosis which varies in severity and clinical presentation
Prospective surveillance (2015–2017) shows 7/356 (2.2%) isolates were resistant to at least one triazole antifungals demonstrating an increase in incidence of triazole-resistant A. fumigatus in our laboratory
Among five isolates collected from 2015 to 2017 and available for molecular testing, three harbored TR34/L98H alteration in the cyp51A gene that are associated with the acquisition of resistance in the non-patient environment

Summary

Introduction

Aspergillus fumigatus is a ubiquitous ascomycete mold and the primary etiologic agent of aspergillosis which varies in severity and clinical presentation. These manifestations include a spectrum of conditions including colonization, allergic response in allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis, aspergilloma, and to the most severe form, invasive aspergillosis (Kosmidis and Denning, 2015). Triazoles have been the most widely used antifungal agents in prophylaxis and treatment of Aspergillus-related infections (Verweij et al, 2015). Since the late 2000s there has been a steady increase in the number of reported resistance to azole antifungals in A. fumigatus, causing a major clinical concern with subsequent treatment failure among some patients (Verweij et al, 2007; Chowdhary et al, 2013). The emergence and global spread of azole-resistant isolates led to a fundamental question as to whether first line clinical use of mold-active triazoles can be retained (Verweij et al, 2015)

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