Activities of micafungin against 315 invasive clinical isolates of fluconazole-resistant Candida spp

Abstract

Micafungin is a new echinocandin exhibiting broad-spectrum activity against Candida spp. The activity of the echinocandins against Candida species known to express intrinsic or acquired resistance to fluconazole is of interest. We determined the MICs of micafungin and caspofungin against 315 invasive clinical (bloodstream and other sterile-site) isolates of fluconazole-resistant Candida species obtained from geographically diverse medical centers between 2001 and 2004. MICs were determined using broth microdilution according to the CLSI reference method M27-A2. RPMI 1640 was used as the test medium, and we used the MIC endpoint of prominent growth reduction at 24 h. Among the 315 fluconazole-resistant Candida isolates, 146 (46%) were C. krusei, 110 (35%) were C. glabrata, 41 (13%) were C. albicans, and 18 (6%) were less frequently isolated species. Micafungin had good in vitro activity against all fluconazole-resistant Candida spp. tested; the MICs at which 50% (MIC(50)) and 90% (MIC(90)) of isolates were inhibited were 0.03 microg/ml and 0.06 microg/ml, respectively. All the fluconazole-resistant Candida spp. were inhibited at a micafungin MIC that was </=1 microg/ml. Among the most common fluconazole-resistant Candida spp. tested in the collection, C. glabrata exhibited the lowest micafungin MICs (MIC(90), </=0.015 microg/ml), followed by C. albicans (MIC(90), 0.03 microg/ml) and C. krusei (MIC(90), 0.06 microg/ml). The new echinocandin micafungin has excellent in vitro activity against 315 invasive clinical isolates of fluconazole-resistant Candida, which represents the largest collection to date of fluconazole-resistant Candida isolates tested against micafungin. Micafungin may prove useful in the treatment of infections due to azole-resistant Candida.