Acquired resistance to echinocandins in Candida albicans: case report and review

• Published in: Journal of antimicrobial chemotherapy Vol. 59; no. 6; pp. 1076 - 1083
• Main Authors: Baixench, Marie-Thérèse, Aoun, Naji, Desnos-Ollivier, Marie, Garcia-Hermoso, Dea, Bretagne, Stéphane, Ramires, Sandrine, Piketty, Christophe, Dannaoui, Eric
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.06.2007; Oxford Publishing Limited (England); Oxford University Press (OUP)
• Subjects: 1-3-β-d-glucan synthase; Adult; Amino Acid Sequence; Amino Acid Substitution; Amphotericin B - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal Agents - pharmacology; Antifungal Agents - therapeutic use; Biological and medical sciences; Candida albicans; Candida albicans - drug effects; Candidiasis - drug therapy; Candidiasis - microbiology; Case studies; caspofungin; Drug resistance; Drug Resistance, Fungal - physiology; Drug therapy; Echinocandins; Etest; Fluconazole - pharmacology; Fungi; Genetics; Genotype; HIV Infections - complications; HIV-1; Humans; Life Sciences; Lipopeptides; Lipoproteins - pharmacology; Lipoproteins - therapeutic use; Male; Medical sciences; micafungin; Microbial Sensitivity Tests; Microbiology; Molecular Sequence Data; Mutation; Peptides, Cyclic - pharmacology; Peptides, Cyclic - therapeutic use; Pharmacology. Drug treatments; Pyrimidines - therapeutic use; Test methods; Treatment Failure; Triazoles - therapeutic use; Voriconazole; 1-3-β; glucan synthase; Etest; caspofungin; micafungin; Candida albicans; Yeast; Enzyme; Acquired; Transferases; Glycosyltransferases; Enzyme inhibitor; 1,3-β-Glucan synthase; 1-3-p-D-glucan synthase; Review; Synthase; Micafungin; Echinocandine derivatives; Fungi; Case study; Glucan; Resistance; Antifungal agent; Caspofungin; Hexosyltransferases; Fungi Imperfecti; Bibliographic review; Thallophyta; 1-3-Beta-D-Glucan synthase
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkm095

Objectives A patient with Candida albicans thrush and oesophagitis was treated with high doses of caspofungin but treatment eventually failed. Four C. albicans isolates were serially recovered before and after caspofungin treatment. A microbiological study was performed to characterize these four isolates. Methods In vitro antifungal susceptibility testing was performed by the EUCAST reference method in RPMI and AM3 and by Etest®. Molecular typing of the four isolates was done by sizing three polymorphic microsatellite markers. To look for specific mutations, sequencing of a region of the gene encoding the 1-3-β-d-glucan synthase was performed for the four isolates. Results In vitro antifungal susceptibility testing showed an increase in both caspofungin and micafungin MICs for the two isolates recovered after caspofungin treatment failure. The best discrimination between the pre-treatment and post-treatment isolates was obtained with Etest®. Molecular typing of the four isolates showed that the post-treatment isolates with reduced susceptibility were identical to a susceptible pre-treatment isolate, suggesting the acquisition of caspofungin resistance. Sequencing of the gene encoding the 1-3-β-d-glucan synthase showed a mutation responsible for an amino acid change at Phe-641 that could confer reduced susceptibility to both echinocandins. Conclusions Our results indicate that is it useful to perform in vitro susceptibility testing in the cases of clinical failure during caspofungin therapy.