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Antimicrob Agents Chemother. 2018 Feb 23;62(3). pii: e01982-17. doi: 10.1128/AAC.01982-17. Print 2018 Mar.

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

Author information

1
Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
2
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
3
Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Biomédica, Madrid, Spain.
4
Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain.
5
CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain.
6
Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
7
Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain jguineaortega@yahoo.es.
#
Contributed equally

Abstract

We report the mutant prevention concentration (MPC) and mutant selection window (MSW) for micafungin and anidulafungin administered to treat Candida glabrata We also determine the mutation frequency. We studied 20 echinocandin-susceptible, fluconazole-intermediate, and FKS wild-type C. glabrata 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 FKS 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 (Galleria mellonella model) of the resulting individual FKS 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 × 10-8 and 2.8 × 10-8, 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, FKS2 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 FKS2 mutant colonies. Echinocandin concentrations lower than 2 mg/liter can lead to selection of resistance mutations in C. glabrata isolates in vitro.

KEYWORDS:

Candida glabrata; FKS mutation; Galleria mellonella; MPC; MSW; echinocandins

PMID:
29311063
PMCID:
PMC5826129
DOI:
10.1128/AAC.01982-17
[Indexed for MEDLINE]
Free PMC Article

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