Susceptibility Testing of Fungi to Antifungal Drugs.

Maurizio Sanguinetti,Brunella Posteraro

doi:10.3390/jof4030110

Abstract

Susceptibility testing of fungi against antifungal drugs commonly used for therapy is a key component of the care of patients with invasive fungal infections. Antifungal susceptibility testing (AFST) has progressed in recent decades to finally become standardized and available as both Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference methods and in commercial manual/automated phenotypic methods. In clinical practice, the Sensititre YeastOne and Etest methods are widely used for AFST, particularly for sterile site isolates of Candida. Nevertheless, AFST is moving toward new phenotypic methods, such as matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), that are capable of providing rapid, and potentially more actionable, results for the treating clinician. Our objective is to summarize updated data on phenotypic methods for AFST of Candida and Aspergillus species and to assess their significance in view of opposing, but emerging, molecular genotypic methods.

Highlights

Especially those caused by the species Candida and Aspergillus, continue to rise in frequency [1] and, alarmingly, are associated with antifungal resistance [2], which makes the management of patients with such infections challenging [3,4]
Consistent with the role of triazoles in the treatment and/or prophylaxis of invasive aspergillosis [43], Clinical and Laboratory Standards Institute (CLSI)-based epidemiological cutoff values (ECVs) for itraconazole, posaconazole, voriconazole, and, lately, isavuconazole were established for Aspergillus species (A. fumigatus, A. flavus, A. terreus, A. niger, A. nidulans, and A. versicolor) to aid in the early identification of clinical isolates with acquired resistance mechanisms [44,45]
Calculating only for isolates of A. fumigatus, A. flavus, A. terreus, and A. niger, the essential agreement value was unchanged for voriconazole (100%), but increased for posaconazole (98.3%) and decreased for itraconazole (94.9%)

Summary

Introduction

Especially those caused by the species Candida and Aspergillus, continue to rise in frequency [1] and, alarmingly, are associated with antifungal resistance [2], which makes the management of patients with such infections challenging [3,4]. European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference methods currently in place [12,13,14,15], and expansion of commercial and automated methods for AFST [16] All of these achievements increased the likelihood that testing several organism–drug combinations (most notably Candida species and the azole antifungal agents) could usefully influence the selection of therapy, aiding clinicians in the management of difficult-to-treat fungal infections [17]. The objectives of this paper are to provide updates on new data from AFST studies and to discuss how AFST might improve outcomes of invasive fungal infections In view of their clinical importance, we will focus on AFST of Candida and Aspergillus species

Reference AFST Methods

Commercial AFST Methods

Nonconventional Phenotypic Assays for Testing Fungal Susceptibility

Conclusions

Findings

Methods