Molecular mechanisms of acquired antifungal drug resistance in principal fungal pathogens and EUCAST guidance for their laboratory detection and clinical implications
Open accessAbstract
The increasing incidence and changing epidemiology of invasive fungal infections continue to present many challenges to their effective management. The repertoire of antifungal drugs available for treatment is still limited although there are new antifungals on the horizon. Successful treatment of invasive mycoses is dependent on a mix of pathogen-, host- and antifungal drug-related factors. Laboratories need to be adept at detection of fungal pathogens in clinical samples in order to effectively guide treatment by identifying isolates with acquired drug resistance. While there are international guidelines on how to conduct in vitro antifungal susceptibility testing, these are not performed as widely as for bacterial pathogens. Furthermore, fungi generally are recovered in cultures more slowly than bacteria, and often cannot be cultured in the laboratory. Therefore, non-culture-based methods, including molecular tests, to detect fungi in clinical specimens are increasingly important in patient management and are becoming more reliable as technology improves. Molecular methods can also be used for detection of target gene mutations or other mechanisms that predict antifungal drug resistance. This review addresses acquired antifungal drug resistance in the principal human fungal pathogens and describes known resistance mechanisms and what in-house and commercial tools are available for their detection. It is emphasized that this approach should be complementary to culture-based susceptibility testing, given the range of mutations, resistance mechanisms and target genes that may be present in clinical isolates, but may not be included in current molecular assays.
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Wiederhold, N. P., Grabinski, J. L., García‐Effrón, G., Perlin, D. S., & Lee, S. A. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00959-08 · Cited by 51 · see citing works
Visconti, E., Ortona, E., Mencarini, P., Margutti, P., Marinaci, S., Zolfo, M., Siracusano, A., & Tamburrini, E. (2001) · International Journal of Antimicrobial Agents · doi:10.1016/s0924-8579(01)00460-5 · Cited by 50 · see citing works
Sulfa Resistance and Dihydropteroate Synthase Mutants in RecurrentPneumocystis cariniiPneumonia
Nahimana, A., Rabodonirina, M., Helweg‐Larsen, J., Meneau, I., Francioli, P. B., Billé, J., & Hauser, P. M. (2003) · Emerging infectious diseases · doi:10.3201/eid0907.020753 · Cited by 50 · see citing works
Júnior, L. R. B., Gast, C. E., Bruzual, I., & Wong, B. (2015) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dku554 · Cited by 49 · see citing works
Compensatory expression of multidrug-resistance genes encoding ABC transporters in dermatophytes
Martins, M. P., Franceschini, A. C. C., Jacob, T. R., Rossi, A., & Martinez-Rossi, N. M. (2016) · Journal of Medical Microbiology · doi:10.1099/jmm.0.000268 · Cited by 49 · see citing works
The first report of terbinafine resistance Microsporum canis from a cat
Hsiao, Y., Chen, C., Han, H. S., et al. (2018) · Journal of Veterinary Medical Science · doi:10.1292/jvms.17-0680 · Cited by 49 · see citing works
Shankarnarayan, S. A., Shaw, D., Sharma, A., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-58187-0 · Cited by 48 · see citing works
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Molecular Detection of Azole-Resistant Aspergillus fumigatus in Clinical Samples
Buil, J. B., Zoll, J., Verweij, P. E., & Melchers, W. J. G. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00515 · Cited by 47 · see citing works
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Flagged first, then by citations
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Cited by
Sorted by citations
An update on current and novel molecular diagnostics for the diagnosis of invasive fungal infections
Jenks, J. D., White, P. L., Kidd, S. E., Goshia, T., Fraley, S. I., Hoenigl, M., & Thompson, G. R. (2023) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2023.2267977 · Cited by 61 · see citing works
Self-citationInsight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance
Su, Y., Li, Y., Yi, Q., Xu, Y., Sun, T., & Li, Y. (2025) · Journal of Fungi · doi:10.3390/jof11020143 · Cited by 18 · see citing works
“…spp., upregulation of the efflux transporter genes CDR1 , MDR1 and mutations in transcriptional factor TAC1B and in the genes ERG11 and ERG3 [82,84–87], which result in for example, primary sequence changes Y132F and R398I in C. parapsilosis lanosterol 14 α -demethylase [85], have been…”
Influential
- Authors
- Rogers, T. R., Verweij, P. E., Castanheira, M., Dannaoui, E., White, P. L., Arendrup, M. C., Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST), Arendrup, M. C., Arikan-Akdagli, S., Barchiesi, F., Buil, J., Castanheira, M., Chryssanthou, E., Friberg, N., Guinea, J., Hamal, P., Hilmarsdottir, I., Klimko, N., Kurzai, O., Lagrou, K., Lass-Flörl, C., Matos, T., Meletiadis, J., Moore, C., Muehlethaler, K., & Rogers, T. R.
- Affiliations
- Department of Clinical Microbiology, Trinity College Dublin, St James’s Hospital Campus , Dublin 8 , Ireland
- Radboud University Nijmegen (NL)
- JMI Laboratories, North Liberty , IA , USA
- Unité de parasitologie-mycologie, service de microbiologie, hôpital européen Georges-Pompidou, AP-HP , Paris , France
- University Hospital of Wales (GB)
- Unit of Mycology , Statens Serum Institut, Copenhagen , Denmark
- Statens Serum Institut (DK)
- Université Paris Cité (FR)
- ORCID
- Venue
- Journal of Antimicrobial Chemotherapy
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-06-15
- Volume
- 77
- Issue
- 8
- Pages
- 2053-2073
- ISSN
- 0305-7453 (ISSN-L)
- 1460-2091
- PMC
- PMC9333407
- OpenAlex
- W4282963864
- Cited by
- 82
- References
- 269
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 20 · 2023: 21 · 2022: 4
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Antimicrobial Chemotherapy (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
- Lirias (submittedVersion, cc-by-nc)
- HAL (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Pfizer
- Bayer
- GlaxoSmithKline
- Novartis
- Gilead Sciences
- Beth Israel Deaconess Medical Center
- University of Southern California
- Wayne State University
- Tufts Medical Center
- F. Hoffmann-La Roche
- Medpace
- Harvard University
- University of Texas Southwestern Medical Center
- University of North Texas
- Cidara Therapeutics
- GenePOC
- Medicines Company
- Melinta Therapeutics
- Amplyx
- Boston Pharmaceuticals
- Achaogen
- Entasis Therapeutics
- Albany College of Pharmacy and Health Sciences
- Nabriva Therapeutics
- Insmed
- National University of Singapore
- European Society of Clinical Microbiology and Infectious Diseases
- University of Queensland
- Meiji Seika Pharma
- North Bristol NHS Trust
- Astellas Pharma
- Shionogi
- Radboud Universitair Medisch Centrum
- Astellas Foundation for Research on Metabolic Disorders
- Basilea Pharmaceutica
- Pfizer Healthcare Ireland
- Wockhardt
- Idorsia Pharmaceuticals
- Dr. Falk Pharma
- TenNor Therapeutics
- Roivant Sciences
- National Institutes of Health
- U.S. Food and Drug Administration
- Allergan
- Medical Center, University of Rochester
- 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
- invasive fungal infections, antifungal susceptibility testing, EUCAST guidelines, resistance mechanisms, clinical isolates, antifungal agents
- MeSH terms
- Invasive Fungal Infections, Antifungal Agents, Fungi, Humans, Laboratories, Microbial Sensitivity Tests, Drug Resistance, Fungal
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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