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Amphotericin B and Caspofungin Resistance in Candida glabrata Isolates Recovered from a Critically Ill Patient
Abstract
BACKGROUND: Consecutive Candida glabrata isolates recovered from a patient in an intensive care unit were resistant to amphotericin B (minimum inhibitory concentration, up to 32 mu g/mL; determined by Etest [AB Biodisk]). Analyses at the national reference laboratory showed that some isolates were also resistant to azoles and caspofungin. In this study, 4 isolates were studied thoroughly using susceptibility assays and a mouse model and to determine clonality. METHODS: Different broth microdilution tests, Etests, and time-kill studies for antifungals were performed in different media. Three of the 4 isolates were examined in an in vivo experiment, in which mice were challenged intravenously with 1 of 3 isolates and treated daily with amphotericin B, caspofungin, or saline. For the clonality studies, arbitrarily primed polymerase chain reaction (PCR) was performed with the 4 isolates, 8 isolates obtained from nonrelated patients, and a reference strain. RESULTS: The murine model indicated that 1 isolate was resistant to amphotericin B, 1 had intermediate susceptibility, and 1 was fully susceptible. Two of the 3 isolates were resistant to caspofungin. Microdilution methods did not reliably differentiate between amphotericin B-susceptible and -resistant isolates. All assays identified caspofungin-susceptible and -resistant isolates. Arbitrarily primed PCR showed that the 4 isolates probably were of clonal origin. CONCLUSIONS: We have documented the emergence of amphotericin B-resistant and caspofungin-resistant C. glabrata isolates during treatment of a critically ill liver transplant recipient. Only the Etest predicted amphotericin B resistance in the isolates. We recommend that important fungal strains recovered from patients who are receiving antifungal therapy should be tested for susceptibility to the antifungal drug used, because resistance can be present initially or may occur during treatment.
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“Importantly, instances of cross-resistance towards amphortericin B and azoles or echinocandinds in Candida have also been reported [50,51,52,53].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [50]
In the citing paper
“However, reports of echinocandin resistance in patients with infections due to C. albicans, C. glabrata, C. tropicalis, and C. krusei are rising [111–116].”
From Candida Infections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents (2013) · cites this paper as [112]
In the citing paper
“Additionally, the latest cross-resistance between amphotericin B and azoles or caspofungin in Candida species are increasingly worrying [103,194,195,196,197].”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [194]
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Metadata
- Authors
- Krogh-Madsen, M., Arendrup, M. C., Heslet, L., & Knudsen, J. D.
- Affiliations
- Hvidovre Hospital (DK)
- Statens Serum Institut (DK)
- Corresponding author
- Knudsen, J. D.
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-04-01
- Volume
- 42
- Issue
- 7
- Pages
- 938-944
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- OpenAlex
- W2106522725
- Cited by
- 201
- References
- 21
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 11 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 14 · 2015: 9 · 2014: 15 · 2013: 6 · 2012: 20
- FWCI
- 13.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Fungal Plant Pathogen Control
- Life Sciences › Immunology and Microbiology › Microbiology › Yeasts and Rust Fungi Studies
- Keywords
- Candida glabrata, amphotericin B resistance, caspofungin resistance, antifungal resistance, critically ill patients, liver transplant recipients, clonality, E-test, antifungal susceptibility testing, time-kill assay, mouse model, azole resistance
- MeSH terms
- Caspofungin, Aged, Amphotericin B, Animals, Antifungal Agents, Candidiasis, Female, Humans, Microbial Sensitivity Tests, Peptides, Cyclic, Polymerase Chain Reaction, Critical Illness, Candida glabrata, Mice, Echinocandins, Lipopeptides
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