title: Breakpoints for antifungal agents: an update from EUCAST focussing on echinocandins against Candida spp. and triazoles against Aspergillus spp.
abstract: Candida and Aspergillus infections have emerged as significant pathogens in recent decades. During this same time, broad spectrum triazole and echinocandin antifungal agents have been developed and increasingly used. One consequence of widespread use is leading to the emergence of mutants with acquired resistance mutations. Therefore, accurate susceptibility testing and appropriate clinical breakpoints for the interpretation of susceptibility results have become increasingly important. Here we review the underlying methodology by which breakpoints have been selected by EUCAST (European Committee on Antimicrobial Susceptibility Testing). Five parameters are evaluated: dosing regimens used; EUCAST MIC distributions from multiple laboratories, species and compound specific epidemiological cut off values (upper MIC limits of wild type isolates or ECOFFs), pharmacokinetic/pharmacodynamic relationships and targets associated with outcome and finally clinical data by species and MIC when available. The general principles are reviewed followed by a detailed review of the individual aspects for Candida species and the three echinocandins and for Aspergillus and the three mould-active azoles. This review provides an update of the subcommittee on antifungal susceptibility testing (AFST) of the EUCAST methodology and summarises the current EUCAST breakpoints for Candida and Aspergillus. Recommendations about applicability of antifungal susceptibility testing in the routine setting are also included.
authors.affiliation: Unit of Mycology, Dept. Microbiology & Infection Control, Statens Serum Institut, Copenhagen, Denmark. Electronic address: maca@ssi.dk.
authors.forename: Maiken C
authors.initials: MC
authors.lastname: Arendrup
authors.affiliation: National Center for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Cuenca-Estrella
authors.affiliation: Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lass-Flörl
authors.affiliation: Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.
authors.forename: William W
authors.initials: WW
authors.lastname: Hope
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D002175:Candida / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D014230:Triazoles
keywords: Acquired resistance; Aspergillus; Azoles; Breakpoints; CLSI; Candida; EUCAST; Echinocandins; MIC; Susceptibility testing