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Clin Infect Dis. 2015 Dec 1;61 Suppl 6:S612-7. doi: 10.1093/cid/civ791.

Echinocandin Resistance in Candida.

Author information

1
Public Health Research Institute, New Jersey Medical School-Rutgers Biomedical and Health Sciences, Newark.

Abstract

Invasive fungal infections are an important infection concern for patients with underlying immunosuppression. Antifungal therapy is a critical component of patient care, but therapeutic choices are limited due to few drug classes. Antifungal resistance, especially among Candida species, aggravates the problem. The echinocandin drugs (micafungin, anidulafungin, and caspofungin) are the preferred choice to treat a range of candidiasis. They target the fungal-specific enzyme glucan synthase, which is responsible for the biosynthesis of a major cell wall polymer. Therapeutic failure involves acquisition of resistance, although it is a rare event among most Candida species. However, in some settings, higher-level resistance has been reported among Candida glabrata, which is also frequently resistant to azole drugs, resulting in difficult-to-treat multidrug-resistant strains. The mechanism of echinocandin resistance involves amino acid changes in "hot spot" regions of FKS-encoded subunits of glucan synthase, which decreases the sensitivity of enzyme to drug, resulting in higher minimum inhibitory concentration values. The cellular processes promoting the formation of resistant FKS strains involve complex stress response pathways that yield a variety of adaptive compensatory genetic responses. Standardized broth microdilution techniques can be used to distinguish FKS mutant strains from wild type, but testing C. glabrata with caspofungin should be approached cautiously. Finally, clinical factors that promote echinocandin resistance include prophylaxis, host reservoirs including biofilms in the gastrointestinal tract, and intra-abdominal infections. An understanding of clinical and molecular factors that promote echinocandin resistance is critical to develop better diagnostic tools and therapeutic strategies to overcome resistance.

KEYWORDS:

Candida; FKS; caspofungin; echinocandin; micafungin

PMID:
26567278
PMCID:
PMC4643482
DOI:
10.1093/cid/civ791
[Indexed for MEDLINE]
Free PMC Article

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