Journal Article

Amphotericin B and Caspofungin Resistance in <i>Candida glabrata</i> Isolates Recovered from a Critically Ill Patient

Mikkel Krogh-Madsen, Maiken Cavling Arendrup, Lars Heslet and Jenny Dahl Knudsen

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 42, issue 7, pages 938-944
Published in print April 2006 | ISSN: 1058-4838
Published online April 2006 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/500939
Amphotericin B and Caspofungin Resistance in Candida glabrata Isolates Recovered from a Critically Ill Patient

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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 µg/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.

Journal Article.  3464 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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