title: In vitro activity of a new oral glucan synthase inhibitor (MK-3118) tested against Aspergillus spp. by CLSI and EUCAST broth microdilution methods.
abstract: MK-3118, a glucan synthase inhibitor derived from enfumafungin, and comparator agents were tested against 71 Aspergillus spp., including itraconazole-resistant strains (MIC, ≥ 4 μg/ml), using CLSI and EUCAST reference broth microdilution methods. The CLSI 90% minimum effective concentration (MEC(90))/MIC(90) values (μg/ml) for MK-3118, amphotericin B, and caspofungin, respectively, were as follows: 0.12, 2, and 0.03 for Aspergillus flavus species complex (SC); 0.25, 2, and 0.06 for Aspergillus fumigatus SC; 0.12, 2, and 0.06 for Aspergillus terreus SC; and 0.06, 1, and 0.03 for Aspergillus niger SC. Essential agreement between the values found by CLSI and EUCAST (± 2 log(2) dilution steps) was 94.3%. MK-3118 was determined to be a potent agent regardless of the in vitro method applied, with excellent activity against contemporary wild-type and itraconazole-resistant strains of Aspergillus spp.
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA. michael-pfaller@jmilabs.com
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pfaller
authors.forename: Shawn A
authors.initials: SA
authors.lastname: Messer
authors.forename: Mary R
authors.initials: MR
authors.lastname: Motyl
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects*; D001231:Aspergillus flavus / Q000187:drug effects; D001232:Aspergillus fumigatus / Q000187:drug effects; D001234:Aspergillus niger / Q000187:drug effects; D000077336:Caspofungin; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D006027:Glycosides / Q000494:pharmacology*; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D006027:Glycosides; D055666:Lipopeptides; D014315:Triterpenes; D000666:Amphotericin B; C569338:ibrexafungerp; D005964:Glucosyltransferases; C040232:glucan synthase; D000077336:Caspofungin