title: Echinocandin and triazole antifungal susceptibility profiles for clinical opportunistic yeast and mold isolates collected from 2010 to 2011: application of new CLSI clinical breakpoints and epidemiological cutoff values for characterization of geographic and temporal trends of antifungal resistance.
abstract: The SENTRY Antimicrobial Surveillance Program monitors global susceptibility and resistance rates of newer and established antifungal agents. We report the echinocandin and triazole antifungal susceptibility patterns for 3,418 contemporary clinical isolates of yeasts and molds. The isolates were obtained from 98 laboratories in 34 countries during 2010 and 2011. Yeasts not presumptively identified by CHROMagar, the trehalose test, or growth at 42°C and all molds were sequence identified using internal transcribed spacer (ITS) and 28S (yeasts) or ITS, translation elongation factor (TEF), and 28S (molds) genes. Susceptibility testing was performed against 7 antifungals (anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole, and voriconazole) using CLSI methods. Rates of resistance to all agents were determined using the new CLSI clinical breakpoints and epidemiological cutoff value criteria, as appropriate. Sequencing of fks hot spots was performed for echinocandin non-wild-type (WT) strains. Isolates included 3,107 from 21 Candida spp., 146 from 9 Aspergillus spp., 84 from Cryptococcus neoformans, 40 from 23 other mold species, and 41 from 9 other yeast species. Among Candida spp., resistance to the echinocandins was low (0.0 to 1.7%). Candida albicans and Candida glabrata that were resistant to anidulafungin, caspofungin, or micafungin were shown to have fks mutations. Resistance to fluconazole was low among the isolates of C. albicans (0.4%), Candida tropicalis (1.3%), and Candida parapsilosis (2.1%); however, 8.8% of C. glabrata isolates were resistant to fluconazole. Among echinocandin-resistant C. glabrata isolates from 2011, 38% were fluconazole resistant. Voriconazole was active against all Candida spp. except C. glabrata (10.5% non-WT), whereas posaconazole showed decreased activity against C. albicans (4.4%) and Candida krusei (15.2% non-WT). All agents except for the echinocandins were active against C. neoformans, and the triazoles were active against other yeasts (MIC90, 2 μg/ml). The echinocandins and triazoles were active against Aspergillus spp. (MIC90/minimum effective concentration [MEC90] range, 0.015 to 2 μg/ml), but the echinocandins were not active against other molds (MEC90 range, 4 to >16 μg/ml). Overall, echinocandin and triazole resistance rates were low; however, the fluconazole and echinocandin coresistance among C. glabrata strains warrants continued close surveillance.
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA. mike-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: Leah N
authors.initials: LN
authors.lastname: Woosley
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D054714:Echinocandins / Q000494:pharmacology*; D005658:Fungi / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D014943:Global Health; D006801:Humans; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000382:microbiology*; D014230:Triazoles / Q000494:pharmacology*; D015003:Yeasts / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D014230:Triazoles