Enfumafungin Derivative MK-3118 Shows Increased In Vitro Potency against Clinical Echinocandin-Resistant Candida Species and Aspergillus Species Isolates

ABSTRACT MK-3118 is as an orally active new antifungal in the early stage of clinical development that inhibits the biosynthesis of β-(1,3)-glucan. We evaluated the in vitro activity of this compound against wild-type and echinocandin-resistant (ER) isolates containing mutations in the FKS gene(s) of Candida spp. and Aspergillus spp. MK-3118 demonstrated enhanced efficacy for most C. albicans and C. glabrata ER isolates relative to caspofungin, with decreased MICs and half-maximal inhibitory concentrations (IC50s).

[1]  Ronald N. Jones,et al.  Activity of MK-3118, a new oral glucan synthase inhibitor, tested against Candida spp. by two international methods (CLSI and EUCAST). , 2013, The Journal of antimicrobial chemotherapy.

[2]  Ronald N. Jones,et al.  In Vitro Activity of a New Oral Glucan Synthase Inhibitor (MK-3118) Tested against Aspergillus spp. by CLSI and EUCAST Broth Microdilution Methods , 2012, Antimicrobial Agents and Chemotherapy.

[3]  D. Perlin,et al.  Improved Detection of Candida sp. fks Hot Spot Mutants by Using the Method of the CLSI M27-A3 Document with the Addition of Bovine Serum Albumin , 2011, Antimicrobial Agents and Chemotherapy.

[4]  J. Cleary,et al.  Effect of Candida glabrata FKS1 and FKS2 Mutations on Echinocandin Sensitivity and Kinetics of 1,3-β-d-Glucan Synthase: Implication for the Existing Susceptibility Breakpoint , 2009, Antimicrobial Agents and Chemotherapy.

[5]  J. Sobel,et al.  Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  D. Perlin,et al.  Correlating Echinocandin MIC and Kinetic Inhibition of fks1 Mutant Glucan Synthases for Candida albicans: Implications for Interpretive Breakpoints , 2008, Antimicrobial Agents and Chemotherapy.

[7]  Clinical,et al.  Reference method for broth dilution antifungal susceptibility testing of filamentous fungi : Approved standard , 2008 .

[8]  Clinical,et al.  Reference method for broth dilution antifungal susceptibility testing of yeasts : Approved standard , 2008 .

[9]  J. Rex,et al.  Effects of Serum on In Vitro Susceptibility Testing of Echinocandins , 2007, Antimicrobial Agents and Chemotherapy.

[10]  D. Perlin,et al.  A Ser678Pro Substitution in Fks1p Confers Resistance to Echinocandin Drugs in Aspergillus fumigatus , 2007, Antimicrobial Agents and Chemotherapy.

[11]  D. Perlin.  Resistance to echinocandin-class antifungal drugs. , 2007, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[12]  D. Perlin,et al.  Serum Differentially Alters the Antifungal Properties of Echinocandin Drugs , 2007, Antimicrobial Agents and Chemotherapy.

[13]  D. Denning.  Echinocandin antifungal drugs , 2003, The Lancet.

[14]  R. Schwartz,et al.  Discovery of Novel Antifungal (1,3)-β-d-Glucan Synthase Inhibitors , 2000, Antimicrobial Agents and Chemotherapy.

[15]  H Kropp,et al.  Preliminary animal pharmacokinetics of the parenteral antifungal agent MK-0991 (L-743,872) , 1997, Antimicrobial agents and chemotherapy.

[16]  E. Bruck,et al.  National Committee for Clinical Laboratory Standards. , 1980, Pediatrics.

[17]  J. Enders,et al.  Infectious Diseases Society of America. , 1969, Antimicrobial agents and chemotherapy.