Rapid antifungal susceptibility testing by matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis.
Open accessAbstract
The widespread use of antifungal agents, which is likely to expand with their enhanced availability, has promoted the emergence of drug-resistant strains. Antifungal susceptibility testing (AFST) is now an essential procedure for guiding appropriate antifungal therapy. Recently, we developed a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based method that enables the detection of fungal isolates with reduced echinocandin susceptibility, relying on the proteome changes that are detectable after a 15-h exposure of fungal cells to serial drug concentrations. Here, we describe a simplified version of this approach that facilitates discrimination of the susceptible and resistant isolates of Candida albicans after a 3-h incubation in the presence of "breakpoint" level drug concentrations of the echinocandin caspofungin (CSF). Spectra at concentrations of 0 (null), 0.03 (intermediate), and 32 (maximal) μg/ml of CSF were used to create individual composite correlation index (CCI) matrices for 65 C. albicans isolates, including 13 fks1 mutants. Isolates are then classified as susceptible or resistant to CSF if the CCI values of spectra at 0.03 and 32 μg/ml are higher or lower, respectively, than the CCI values of spectra at 0.03 and 0 μg/ml. In this way, the drug resistance of C. albicans isolates to echinocandin antifungals can be quickly assessed. Furthermore, the isolate categorizations determined using MALDI-TOF MS-based AFST (ms-AFST) were consistent with the wild-type and mutant FKS1 genotypes and the AFST reference methodology. The ms-AFST approach may provide a rapid and reliable means of detecting emerging antifungal resistance and accelerating the initiation of appropriate antifungal treatment.
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The performance of commercial susceptibility tests for echinocandins is somewhat more variable.
“The updated antifungal susceptibility testing reference methods identify echinocandin resistant isolates reliably; while the performance of commercial tests is somewhat more variable.”
From Echinocandin resistance: an emerging clinical problem? (2014) · cites this paper as [49]
In one study evaluating the performance of the VITEK system for caspofungin susceptibility, a relatively high number (19.4%) of mutant isolates were mis-classified as susceptible.
“In one such study evaluating the performance the VITEK system for caspofungin susceptibility, a relatively high number (19.4%) of mutant isolate were mis-classified as susceptible (49).”
From Echinocandin resistance: an emerging clinical problem? (2014) · cites this paper as [49]
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- Authors
- Vella, A., De Carolis, E., Vaccaro, L., Posteraro, P., Perlin, D. S., Kostrzewa, M., Posteraro, B., & Sanguinetti, M.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- Institute of Microbiology, Università Cattolica del Sacro Cuore, Rome, Italy
- Clinical Laboratory, Ospedale San Carlo, Rome, Italy
- Rutgers New Jersey Medical School (US)
- Bruker (Germany) (DE)
- ORCID
- Venue
- Journal of Clinical Microbiology
- Publisher
- American Society for Microbiology
- Published
- 2013-09
- Volume
- 51
- Issue
- 9
- Pages
- 2964-2969
- ISSN
- 0095-1137 (ISSN-L)
- 1098-660X
- PMC
- PMC3754633
- OpenAlex
- W2111573375
- Cited by
- 124
- References
- 44
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 7 · 2021: 11 · 2020: 7 · 2019: 11 · 2018: 14 · 2017: 15 · 2016: 11 · 2015: 10 · 2014: 17 · 2013: 3
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Microbiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- National Institutes of Health
- U.S. Food and Drug Administration
- National Institute of Allergy and Infectious Diseases (AI069397, R01AI069397)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- antifungal susceptibility testing, Candida albicans, echinocandin resistance, caspofungin, MALDI-TOF mass spectrometry, proteomic profiling, antifungal resistance
- MeSH terms
- Caspofungin, Antifungal Agents, Candida albicans, Fungal Proteins, Humans, Microbial Sensitivity Tests, Time Factors, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Proteome, Echinocandins, Lipopeptides
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