title: Caspofungin Etest endpoint for Aspergillus isolates shows poor agreement with the reference minimum effective concentration.
abstract: The Clinical and Laboratory Standards Institute (CLSI) M38-A2 reference broth microdilution (BMD) method for the antifungal susceptibility testing of filamentous fungi now includes guidelines for testing echinocandin activity using the minimum effective concentration (MEC) as the endpoint measurement. In this study, we compared the caspofungin Etest MIC on RPMI agar and Mueller-Hinton agar (supplemented with glucose and methylene blue [MGM]) to the BMD MEC for 345 clinical Aspergillus isolates, including A. flavus, A. fumigatus, A. nidulans, A. niger, and A. terreus. The essential agreement (+/-1 log(2) dilution) of the Etest on MGM and RPMI agar with the reference BMD MEC was 18 and 26%, respectively. The geometric mean values for BMD MEC and MGM Etest were 0.137 and 0.024 microg/ml, respectively, and the geometric mean values for BMD and RPMI agar were 0.128 and 0.031 microg/ml, respectively. Comparatively, 91% of paired MGM and RPMI Etest results were within 2 log(2) dilutions of each other and consistently produced clearly defined endpoints. In conclusion, the caspofungin Etest MIC, like the BMD MEC, is a reproducible endpoint but is markedly lower than the reference BMD. In anticipation of susceptibility breakpoint assignments, optimization studies will be required to improve the concordance of these two assays so that the potential for underreporting echinocandin resistance in Aspergillus is mitigated.
authors.affiliation: Division of Medical Microbiology, Department of Laboratory Medicine and Pathology, University of Alberta Hospital, Walter C. Mackenzie Centre 2B3.13, 8440 112 St., Edmonton, Alberta T6G 2J2, Canada. jeff.fuller@albertahealthservices.ca
authors.forename: Jeff
authors.initials: J
authors.lastname: Fuller
authors.forename: Adam
authors.initials: A
authors.lastname: Schofield
authors.forename: Safeer
authors.initials: S
authors.lastname: Jiwa
authors.forename: Crystal
authors.initials: C
authors.lastname: Sand
authors.forename: Brad
authors.initials: B
authors.lastname: Jansen
authors.forename: Robert
authors.initials: R
authors.lastname: Rennie
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology*; D001230:Aspergillus / Q000187:drug effects* / Q000302:isolation & purification; D000077336:Caspofungin; D003470:Culture Media / Q000737:chemistry; D054714:Echinocandins / Q000494:pharmacology*; D006801:Humans; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: D000935:Antifungal Agents; D003470:Culture Media; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin