Vol.58 No.1 January 2010

Antifungal susceptibility testing of micafungin according to CLSI M27-A3 against clinical isolates of Candida species

Fumiaki Ikeda¹⁾, Makoto Suzuki¹⁾, Miyuki Hasegawa¹⁾, Takeshi Saika¹⁾ and Intetsu Kobayashi²⁾

¹⁾Chemotherapy Division, Mitsubishi Chemical Medience Corp., 3-30-1 Shimura, Itabashi-ku, Tokyo, Japan
²⁾School of Nursing Faculty of Medicine, Toho University

Abstract

The Clinical and Laboratory Standards Institute (CLSI) has developed methods for testing the activity of echinocandins including caspofungin, micafungin and anidulafungin against yeasts (M27-A3 and M27-S3). M27-S3 provides interpretative breakpoint MICs of≥2 μg/mL for echinocandins against Candida species.
Micafungin MICs have been conventionally defined as the lowest drug concentration preventing visible growth after 48 h incubation (MIC-0). M27-A3 defined MICs as the lowest drug concentration significantly reducing growth (≥50% inhibition) after 24 h incubation (MIC-2).
We determined micafungin MIC-0 and MIC-2 by broth microdilution methods according to M27-A3 against a total of 848 clinical Candida isolates, including 265 Candida albicans, 136 Candida tropicalis, 100 Candida glabrata, 137 Candida parapsilosis, 103 Candida krusei, and 107 Candida guilliermondii from cases of suspected fungal infection visiting medical facilities in Japan between 2002 and 2008.
No significant difference in MIC₅₀ and MIC₉₀ values was determined as MIC-0 and MIC-2 against isolates of C. albicans, C. tropicalis, C. glabrata, C. parapsilosis, and C. krusei. In contrasts MIC₅₀ and MIC₉₀ against isolates of C. guilliermondii determined by MIC-0 were 4-8 times higher than determined as MIC-2. MIC-0 values against 4 isolates of C. albicans and C. tropicalis were markedly higher than MIC-2 values against the same isolates. Paradoxical growth of these isolates occurred at concentrations above MIC-2 values for micafungin after 48 h incubation.
Based on MIC-2 data, isolates were classified as 'susceptible' and 31 of 828 isolates (3.7%) as 'nonsusceptible' based on MIC-0 data, with 23 of 107 C. guilliermondii isolates (21%) designated nonsusceptible based on MIC-0 data.
Micafungin breakpoint MIC will therefore be additionally studied for isolates identified during postmarket micafungin surveillance.

Key word

Candida spp, micafungin, antifungal activity, CLSI

Received

October 13, 2009

Accepted

December 8, 2009

Jpn. J. Chemother. 58 (1): 1-6, 2010