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 g/ml and 0.06 g/ml, respectively. All the fluconazole-resistant Candida spp. were inhibited at a micafungin MIC that was <1 g/ml. Among the most common fluconazole-resistant Candida spp. tested in the collection, C. glabrata exhibited the lowest micafungin MICs (MIC 90 , <0.015 g/ml), followed by C. albicans (MIC 90 , 0.03 g/ml) and C. krusei (MIC 90 , 0.06 g/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 azoleresistant Candida.In the United States, Candida spp. are the fourth most common cause of nosocomial bloodstream infection (13,14). These infections result in increased mortality (5) and longer hospital stays (3, 18) with associated higher health care costs. Of special concern has been the emergence of non-Candida albicans species exhibiting resistance to the current spectrum of azoles (6,8,(12)(13)(14). Treatment of azole-resistant infections has remained a challenge for clinicians and has driven the need for alternative agents having novel mechanisms of action.The development of the echinocandin class of systemic antifungal agents has added to the limited number of drugs used against Candida spp. In contrast to the azoles, which inhibit ergosterol synthesis, echinocandins interrupt the synthesis of 1,3-␤-D glucan, an important component of the fungal cell wall (2). The echinocandins have been shown to exhibit in vitro activity against both Candida spp. and Aspergillus spp. (4,10,11,15,17,19).Micafungin is the most recently available echinocandin, currently FDA approved for use in esophageal candidiasis and for the prophylaxis of invasive fungal infections in hematopoietic stem cell transplant patients. The activity of micafungin against clinical isolates of azole-resistant Candida spp. is of interest. We examine...

Global Surveillance of In Vitro Activity of Micafungin against Candida : a Comparison with Caspofungin by CLSI-Recommended Methods

“…However, the MICs were read after 48 h of incubation rather than 24 h. Recently, we have tested a smaller collection of 315 fluconazole-resistant isolates of Candida spp. using the CLSI consensus conditions and found excellent activity for both micafungin and caspofungin (6). Although the echinocandins appear to have excellent activity against Candida spp., recent reports describing the development of resistance to caspofungin and micafungin during treatment of endocarditis (7) and to caspofungin during treatment of esophagitis (4) raise the specter of the emergence of echinocandin-resistant Candida species.…”

“…In the present study we have employed the optimal testing conditions described previously (6,9,14), to examine geographic trends in the activity of micafungin against an interna- 3 of Candida pelliculosa, and 1 each of Candida rugosa and Candida zeylanoides. All isolates were obtained from blood or other normally sterile sites and represented individual infectious episodes.…”

“…All isolates were obtained from blood or other normally sterile sites and represented individual infectious episodes. The isolates were collected at the individual study sites and were sent to the University of Iowa (Iowa City) for identification and susceptibility testing as described previously (6,(13)(14)(15)(16). The isolates were identified by standard methods (3) and stored as water suspensions until used in the study.…”

Expansion of a recent class of broad-spectrum antifungal agents: the echinocandins

“…In one study of 315 fluconazoleresistant isolates, the overall MIC90 was 0.06 mcg/mL; C. glabrata isolates were the most sensitive to micafungin, with an overall MIC90 of 0.015 mcg/mL for 110 isolates (22). A second study also found excellent activity against all species of Candida, although MICs for C. parapsilosis were among the highest, ranging from 0.5 to 2 mcg/mL (23).The third study found micafun- Table 1.…”

“…Three studies evaluated the in vitro activity of micafungin against 551 clinical Candida isolates (22,23,35). In one study of 315 fluconazoleresistant isolates, the overall MIC90 was 0.06 mcg/mL; C. glabrata isolates were the most sensitive to micafungin, with an overall MIC90 of 0.015 mcg/mL for 110 isolates (22).…”