Activity of MK-3118, a new oral glucan synthase inhibitor, tested against Candida spp. by two international methods (CLSI and EUCAST)

• Published in: Journal of antimicrobial chemotherapy Vol. 68; no. 4; pp. 858 - 863
• Main Authors: Pfaller, Michael A, Messer, Shawn A, Motyl, Mary R, Jones, Ronald N, Castanheira, Mariana
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01-04-2013
• Subjects: Antifungal agents; Antifungal Agents - pharmacology; Bacteria; Bone mineral density; Candida - drug effects; Candida - isolation & purification; Candida albicans; Candida glabrata; Candida krusei; Candida parapsilosis; Candida tropicalis; Candidiasis - microbiology; Caspofungin; Clinical isolates; Comparative analysis; Drug resistance; glucans; Glucosyltransferases - antagonists & inhibitors; Glycosides - pharmacology; Humans; Language; Microbial Sensitivity Tests; Minimum inhibitory concentration; Mutation; Spectrophotometry; Time Factors; Triterpenes - pharmacology
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dks466

To evaluate the activity of the orally bioavailable enfumafungin derivative MK-3118 and comparator antifungal agents tested against a collection of 113 clinical isolates of Candida spp. using CLSI and EUCAST broth microdilution (BMD) methods.
Candida spp. isolates (n=113) were tested by CLSI and EUCAST methods. The collection contained 29 Candida albicans, 29 Candida glabrata, 21 Candida tropicalis, 15 Candida parapsilosis and 19 Candida krusei, including azole- and echinocandin-resistant isolates. CLSI and EUCAST MIC endpoints of 50% and 100% inhibition were determined using visual reading at 24 and 48 h of incubation and spectrophotometric reading at 24 h of incubation, respectively.
MK-3118 CLSI MIC results ranged from 0.06 to 16 mg/L depending on species, duration of incubation and endpoint criteria (EC) used. Comparison of CLSI and EUCAST following 24 h of incubation and either 50% or 100% inhibition revealed an essential agreement (EA; ± 2 doubling dilutions) of 99.1% using the 50% inhibition EC and 93.2% using the 100% inhibition EC. MK-3118 (24 h of incubation and 50% EC) was active against all the species tested and displayed similar potency to caspofungin (using CLSI BMD) against C. albicans (MIC90, 1 and 2 mg/L, respectively), C. tropicalis (1 and 1 mg/L, respectively), C. parapsilosis (0.5 and 0.5 mg/L, respectively) and C. krusei (2 and 1 mg/L, respectively), but was 8-fold more potent than caspofungin against C. glabrata strains (MIC90, 2 and 16 mg/L, respectively). MK-3118 was active against fluconazole-resistant strains as well as caspofungin-resistant strains with documented fks mutations.
MK-3118 was documented to have potent in vitro activity against Candida spp. when tested by both CLSI and EUCAST BMD methods, with the highest overall EA (99.1%) obtained when MK-3118 MIC results were read after 24 h of incubation using a partial inhibition EC (50%).