Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy

Details

Serval ID
serval:BIB_77343E221E9E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy
Journal
Antimicrobial Agents and Chemotherapy
Author(s)
Asner S, Giulieri , Diezi , Marchetti , Sanglard 
ISSN
0066-4804 (Print)
1098-6596 (Electronic)
ISSN-L
0066-4804
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
59
Number
12
Pages
7715-7722
Language
english
Notes
Publication types: Mechanisms of Resistance ; research-article Identifiant PubMed Central: PMC4649199
Abstract
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.
Keywords
Antifungal Agents/therapeutic use, Candida/drug effects, Candidiasis/drug therapy, Candidiasis/microbiology, DNA, Fungal/genetics, Drug Resistance, Multiple, Fungal/genetics, Leukemia, Myeloid, Acute/complications, Leukemia, Myeloid, Acute/drug therapy, Mannans/metabolism, Mutation/genetics, beta-Glucans/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
11/10/2016 15:30
Last modification date
20/08/2019 14:34
Usage data