Amphotericin B and Caspofungin Resistance in Candida glabrata Isolates Recovered from a Critically Ill Patient

• Published in: Clinical infectious diseases Vol. 42; no. 7; pp. 938 - 944
• Main Authors: Krogh-Madsen, Mikkel, Arendrup, Maiken Cavling, Heslet, Lars, Knudsen, Jenny Dahl
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-04-2006; University of Chicago Press; Oxford University Press
• Subjects: Aged; Amphotericin B - pharmacology; Animal models; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - pharmacology; Antifungals; Antimicrobials; Antiparasitic agents; Articles and Commentaries; Biological and medical sciences; Body fluids; Candida glabrata; Candida glabrata - drug effects; Candida glabrata - genetics; Candida glabrata - isolation & purification; Candidiasis - drug therapy; Clinical outcomes; Critical care; Critical Illness; Drug resistance; Echinocandins; Female; Genetic diversity; Hospitals; Humans; Infections; Infectious diseases; Intensive care units; Lipopeptides; Liver; Medical sciences; Mice; Microbial Sensitivity Tests; Patients; Peptides, Cyclic - pharmacology; Pharmacology. Drug treatments; Polymerase Chain Reaction; Testing; Human; Critically ill; Candida glabrata; Echinocandine derivatives; Fungi; Infection; Resistance; Antiprotozoal agent; Antibiotic; Antifungal agent; Amphotericin B; Polyenic compound; Caspofungin; Parasiticide; Fungi Imperfecti; Thallophyta
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/500939

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.