Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy.

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Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_2355233CE663
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy.
Périodique
Antimicrobial Agents and Chemotherapy
Auteur(s)
Asner S.A., Giulieri S., Diezi M., Marchetti O., Sanglard D.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
59
Numéro
12
Pages
7715-7722
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins. A few missense mutations in the C. lusitaniae FKS1 hot spot 1 (HS1) have been reported. We report here the rapid emergence of antifungal resistance in C. lusitaniae isolated during therapy with amphotericin B (AMB), caspofungin (CAS), and azoles for treatment of persistent candidemia in an immunocompromised child with severe enterocolitis and visceral adenoviral disease. As documented from restriction fragment length polymorphism (RFLP) and random amplified polymorphic DNA (RAPD) analysis, the five C. lusitaniae isolates examined were related to each other. From antifungal susceptibility and molecular analyses, 5 different profiles (P) were obtained. These profiles included the following: profile 1 (P1) (CAS MIC [μg/ml], 0.5; fluconazole [FLC] MIC, 0.25), determined while the patient was being treated with liposomal AMB for 3 months; P2 (FLC MIC [μg/ml], 0.25; CAS MIC, 4), while the patient was being treated with CAS for 2 weeks; P3 (CAS MIC [μg/ml], 0.5; FLC MIC, 32), while the patient was being treated with azoles and CAS initially followed by azoles alone for a week; P4 (CAS MIC [μg/ml], 8; FLC MIC, 8), while the patient was being treated with both drugs for 3 weeks; and P5 (AMB MIC [μg/ml], 0.125; CAS MIC, 8), while the patient was being treated with AMB and FLC for 2 weeks. CAS resistance was associated with resistance not only to micafungin and anidulafungin but also to AMB. Analysis of CAS resistance revealed 3 novel FKS1 mutations in CAS-resistant isolates (S638Y in P2; S631Y in P4; S638P in P5). While S638Y and -P are within HS1, S631Y is in close proximity to this domain but was confirmed to confer candin resistance using a site-directed mutagenesis approach. FLC resistance could be linked with overexpression of major facilitator gene 7 (MFS7) in C. lusitaniae P2 and P4 and was associated with resistance to 5-flurocytosine. This clinical report describes resistance of C. lusitaniae to all common antifungals. While candins or azole resistance followed monotherapy, multidrug antifungal resistance emerged during combined therapy.
Mots-clé
Amino Acid Sequence, Antifungal Agents/therapeutic use, Candida/drug effects, Candidiasis/drug therapy, Candidiasis/microbiology, DNA, Fungal/genetics, Drug Monitoring, Drug Resistance, Multiple, Fungal/genetics, Female, Humans, Immunocompromised Host, Infant, Leukemia, Myeloid, Acute/complications, Leukemia, Myeloid, Acute/drug therapy, Mannans/metabolism, Microbial Sensitivity Tests, Molecular Sequence Data, Mutation/genetics, Polymorphism, Restriction Fragment Length, beta-Glucans/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/09/2016 20:43
Dernière modification de la notice
22/01/2020 8:08
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