Mutant Prevention Concentration and Mutant Selection Window of Micafungin and Anidulafungin in Clinical Candida glabrata Isolates

• Published in: Antimicrobial agents and chemotherapy Vol. 62; no. 3
• Main Authors: Bordallo-Cardona, María Ángeles, Marcos-Zambrano, Laura Judith, Sánchez-Carrillo, Carlos, de la Pedrosa, Elia Gómez G, Cantón, Rafael, Bouza, Emilio, Escribano, Pilar, Guinea, Jesús
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.03.2018
• Subjects: Anidulafungin; Anidulafungin - pharmacology; Antifungal Agents; Antifungal Agents - pharmacology; Candida glabrata; Candida glabrata - drug effects; Candida glabrata - genetics; Drug Resistance, Fungal - genetics; Echinocandins - pharmacology; Humans; Micafungin; Micafungin - pharmacology; Mutation - genetics; Susceptibility; MSW; echinocandins; MPC; FKS mutation; Candida glabrata; Galleria mellonella
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.01982-17

We report the mutant prevention concentration (MPC) and mutant selection window (MSW) for micafungin and anidulafungin administered to treat We also determine the mutation frequency. We studied 20 echinocandin-susceptible, fluconazole-intermediate, and wild-type isolates. Adjusted inocula were stroked directly onto Sabouraud agar plates containing different concentrations of micafungin or anidulafungin and visually inspected daily for up to 5 days of incubation. Individual colonies growing on the plates containing echinocandins at 1 mg/liter were selected for antifungal susceptibility testing. The genes of the resulting individual phenotypically resistant colonies were sequenced, and the MPC, MSW, and mutation frequency were determined. Biofilm was quantified, and the growth kinetics and virulence ( model) of the resulting individual mutant colonies were studied. For micafungin and anidulafungin, we found similar results for the MPC (0.06 to 2 mg/liter and 0.25 to 2 mg/liter, respectively), MSW (0.015 to 2 mg/liter for both echinocandins), and mutation frequency (3.7 × 10 and 2.8 × 10 , respectively). A total of 12 isolates were able to grow at 1 mg/liter on echinocandin-containing plates, yielding a total of 32 phenotypically resistant colonies; however, mutations (ΔF658, S663P, W715L, and E655A) were observed only in 21 colonies. We did not find differences in biofilm formation, the kinetic parameters studied, or the median survival of larvae infected by wild-type isolates and the resulting individual mutant colonies. Echinocandin concentrations lower than 2 mg/liter can lead to selection of resistance mutations in isolates .