期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 54, 期 1, 页码 426-439出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01256-09
关键词
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资金
- Astellas Pharma
- Merck Co. Inc
- Pfizer Aps
- NIH [AI069397]
- Gilead
- Merch Sharp Dohme
- Schering Plough
- Myconostica
- Gilead Sciences
- Soria Melguizo SA
- European Union
- Spanish Agency for International Cooperation
- Spanish Ministry of Culture and Education
- Spanish Health Research Fund
- Instituto de Salud Carlos III
- Ramon Areces Foundation
- Mutua Madrilena Foundation
- ALBAN program
- Mutua Madrilen a Foundation
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI069397] Funding Source: NIH RePORTER
This study compared nine susceptibility testing methods and 12 endpoints for anidulafungin, caspofungin, and micafungin with the same collection of blinded FKS hot spot mutant (n = 29) and wild-type isolates (n = 94). The susceptibility tests included EUCAST Edef 7.1, agar dilution, Etest, and disk diffusion with RPMI-1640 plus 2% glucose (2G) and IsoSensitest-2G media and CLSI M27A-3. Microdilution plates were read after 24 and 48 h. The following test parameters were evaluated: fks hot spot mutants overlapping the wild-type distribution, distance between the two populations, number of very major errors (VMEs; fks mutants misclassified as susceptible), and major errors (MEs; wild-type isolates classified as resistant) using a wild-type-upper-limit value (WT-UL) (two twofold-dilutions higher than the MIC50) as the susceptibility breakpoint. The methods with the lowest number of errors (given as VMEs/MEs) across the three echinocandins were CLSI (12%/1%), agar dilution with RPMI-2G medium (14%/0%), and Etest with RPMI-2G medium (8%/3%). The fewest errors overall were observed for anidulafungin (4%/1% for EUCAST, 4%/3% for CLSI, and 3%/9% for Etest with RPMI-2G). For micafungin, VME rates of 10 to 71% were observed. For caspofungin, agar dilution with either medium was superior (VMEs/MEs of 0%/1%), while CLSI, EUCAST with IsoSensitest-2G medium, and Etest were less optimal (VMEs of 7%, 10%, and 10%, respectively). Applying the CLSI breakpoint (S <= 2 mu g/ml) for CLSI results, 89.2% fks hot spot mutants were classified as anidulafungin susceptible, 60.7% as caspofungin susceptible, and 92.9% as micafungin susceptible. In conclusion, no test was perfect, but anidulafungin susceptibility testing using the WT-UL to define susceptibility reliably identified fks hot spot mutants.
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