Amphotericin B and caspofungin resistance in Candida glabrata isolates recovered from a critically ill patient

Krogh-Madsen, M.; Arendrup, M. C.; Heslet, L.; Knudsen, J. D.

doi:10.1086/500939

Cited by 201Antifungal resistance and susceptibilityFungal Plant Pathogen ControlYeasts and Rust Fungi Studies

Amphotericin B and caspofungin resistance in Candida glabrata isolates recovered from a critically ill patient

Krogh-Madsen, M., Arendrup, M. C., Heslet, L., Knudsen, J. D.·2006·Clinical Infectious Diseases

DOI 10.1086/500939

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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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Cross-resistance towards amphotericin B and azoles or echinocandins in Candida has been reported.
“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]
Reports of echinocandin resistance in patients with infections due to C. albicans, C. glabrata, C. tropicalis, and C. krusei are rising.
“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 CandidaInfections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents (2013) · cites this paper as [112]
The latest cross-resistance between amphotericin B and azoles or caspofungin in Candida species is increasingly worrying.
“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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Amphotericin B and caspofungin resistance in Candida glabrata isolates recovered from a critically ill patient. Clin Infect Dis. 2006; 42(7): 938944
Krogh-madsen, M., Arendrup, M. C., Heslet, L., & Knudsen, J. D. (2016)
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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.
ORCID: Arendrup, M. C.
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
DOI: 10.1086/500939
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 › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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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Amphotericin B and caspofungin resistance in Candida glabrata isolates recovered from a critically ill patient

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