Anidulafungin and Micafungin MIC Breakpoints Are Superior to That of Caspofungin for Identifying FKS Mutant Candida glabrata Strains and Echinocandin Resistance

Shields, Ryan K.; Nguyen, M. Hong; Press, Ellen G.; Updike, Cassaundra L.; Clancy, Cornelius J.

doi:10.1128/aac.01451-13

Cited by 58Antifungal resistance and susceptibilityFungal Plant Pathogen ControlFungal and yeast genetics research

Anidulafungin and Micafungin MIC Breakpoints Are Superior to That of Caspofungin for Identifying FKS Mutant Candida glabrata Strains and Echinocandin Resistance

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Shields, Ryan K., Nguyen, M. Hong, Press, Ellen G., Updike, Cassaundra L., Clancy, Cornelius J.·2013·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.01451-13PMC PMC3837909

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Abstract

By CLSI interpretive criteria, anidulafungin and micafungin MICs determined by various methods were sensitive (60 to 70%) and highly specific (94 to 100%) for identifying FKS mutations among 120 Candida glabrata isolates. Anidulafungin and micafungin breakpoints were more specific than CLSI's caspofungin breakpoint in identifying FKS mutant strains and patients with invasive candidiasis who were likely to fail echinocandin treatment (P ≤ 0.0001 for both). Echinocandin MICs were most useful clinically when interpreted in the context of prior echinocandin exposure.

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Echinocandin resistance predominantly emerges under specific drug selection pressure, as evidenced by its strong association with prior echinocandin exposure.
“Clinically, echinocandin resistance predominantly emerges under specific drug selection pressure, as evidenced by their strong association with prior echinocandin exposure [44, 45, 46].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in Candida Glabrata (2026) · cites this paper as [45]
Caspofungin has an inherently lower ability to identify FKS mutations compared to anidulafungin and micafungin, with a 90% sensitivity and 3% specialty.
“caspofungin held an inherit lower ability to identify FKS mutations compared to anidulafungin and micafungin, with a 90% sensitivity and 3% specialty [44, 45].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in Candida Glabrata (2026) · cites this paper as [45]
Caspofungin is unreliable for MIC determination due to high interlaboratory variability.
“Caspofungin has been found to be unreliable for MIC determination due to high interlaboratory variability [33,34,35,36].”
From Treatment of Invasive Candidiasis: A Narrative Review (2018) · cites this paper as [34]

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Self-citation

Caspofungin MICs Correlate with Treatment Outcomes among
Patients, C., Ida Glabrata Invasive, C., & Exposure, E. (2016)
Caspofungin MICs correlate with treatment outcomes among patients with Candida glabrata invasive candidiasis and prior echinocandin exposure.
Shields, R. K., Nguyen, M. H., Press, E. G., Updike, C. L., & Clancy, C. J. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00136-13 · Cited by 105 · see citing works
Self-citation
Optimizing Echinocandin Dosing and Susceptibility Breakpoint Determination via In Vivo Pharmacodynamic Evaluation against Candida glabrata with and without fks Mutations
Lepak, A. J., Castanheira, M., Diekema, D. J., Pfaller, M. A., & Andes, D. R. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01102-12 · Cited by 42 · see citing works
The Presence of an FKS Mutation Rather than MIC Is an Independent Risk Factor for Failure of Echinocandin Therapy among Patients with Invasive Candidiasis Due to Candida glabrata
Shields, R. K., Nguyen, M. H., Press, E. G., Kwa, A. L., Cheng, S., Du, C., & Clancy, C. J. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00027-12 · Cited by 171 · see citing works
Self-citation
Detection of fks gene Hot Spot Mutations in Candida glabrata by CLSI Broth Microdilution Testing of Anidulafungin, Caspofungin and Micafungin Using Epidemiological Cutoff Values
Pfaller, M. A., Woosley, L., Messer, S., Diekema, D. J., Jones, R. J., & Castanheira, M. (2013)

Authors: Shields, R. K., Nguyen, M. H., Press, E. G., Updike, C. L., & Clancy, C. J.
Affiliations: University of Pittsburgh (US)
ORCID: Shields, Ryan K.
Nguyen, M. Hong
Clancy, Cornelius J.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2013-12
Volume: 57
Issue: 12
Pages: 6361-6365
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.01451-13
PMC: PMC3837909
OpenAlex: W2150431004
Cited by: 56
References: 17
Citations by year: 2023: 4 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 8 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 11 · 2014: 8 · 2013: 1
FWCI: 6.05
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Astellas Pharma
National Institutes of Health (UL1TR000005, KL2TR000146)
National Center for Research Resources (KL2RR024154)
National Center for Advancing Translational Sciences
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: Candida glabrata, echinocandin resistance, anidulafungin, micafungin, caspofungin, MIC breakpoints, invasive candidiasis, antifungal susceptibility testing
MeSH terms: Caspofungin, Micafungin, Anidulafungin, Antifungal Agents, Candidiasis, Humans, Microbial Sensitivity Tests, Candida glabrata, Echinocandins, Lipopeptides

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Anidulafungin and Micafungin MIC Breakpoints Are Superior to That of Caspofungin for Identifying FKS Mutant Candida glabrata Strains and Echinocandin Resistance

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