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Breakthrough candidemia due to multidrug-resistant Candida glabrata during prophylaxis with a low dose of micafungin.

ABSTRACT: We identified a case of breakthrough candidemia in a 25-year-old patient receiving micafungin prophylaxis (50 mg/day). Five Candida glabrata isolates were obtained from blood cultures and were classified as multidrug-resistant isolates, since all of them exhibited high MICs for echinocandin and azole drugs. A mutation (S663F) in hot spot 1 of the FKS2 gene was found in all five isolates. This mutation yielded a 1,3-?-D-glucan synthase enzyme with highly reduced sensitivities to echinocandin drugs.

SUBMITTER: Bizerra FC

PROVIDER: S-EPMC4023795 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Breakthrough candidemia due to multidrug-resistant Candida glabrata during prophylaxis with a low dose of micafungin.

Bizerra Fernando César FC Jimenez-Ortigosa Cristina C Souza Ana Carolina R AC Breda Giovanni Luis GL Queiroz-Telles Flávio F Perlin David S DS Colombo Arnaldo L AL

Antimicrobial agents and chemotherapy 20140127 4

We identified a case of breakthrough candidemia in a 25-year-old patient receiving micafungin prophylaxis (50 mg/day). Five Candida glabrata isolates were obtained from blood cultures and were classified as multidrug-resistant isolates, since all of them exhibited high MICs for echinocandin and azole drugs. A mutation (S663F) in hot spot 1 of the FKS2 gene was found in all five isolates. This mutation yielded a 1,3-β-D-glucan synthase enzyme with highly reduced sensitivities to echinocandin drug ...[more]

PMID: 24468776

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Project description:BACKGROUND: Candida glabrata has emerged as an important human pathogen associated with systemic and mucosal infections. Here, we describe isolation of two cholesterol-dependent Candida glabrata strains from a candidemia patient which failed to grow on the media devoid of a cholesterol source. METHODS: Both the isolates were recovered from BACTEC Plus Aerobic/F blood culture bottles of a candidemic patient. Since these isolates failed to grow on Sabouraud dextrose agar, Mueller-Hinton agar and RPMI 1640 agar media, their definitive identification required PCR sequencing of the internally transcribed spacer (ITS)1 and ITS2 regions of rDNA and the D1/D2 region sequences within 26S rRNA gene. The cholesterol auxotrophy was determined by their ability to grow on media containing a cholesterol source. The minimum inhibitory concentrations (MICs) to antifungal agents were determined by Etest. RESULTS: The identity of the isolates was confirmed by sequencing of the ITS1 and ITS2 regions of rDNA and the D1/D2 region sequences within 26S rRNA gene and also by matrix-assisted laser desorption and ionization-time-of-flight mass spectrometry with 99.9% confidence value. Both the isolates showed good growth only when media were supplemented with cholesterol, oxbile or blood. Additionally, these isolates were resistant to amphotericin B (MIC ?32 ?g/ml), fluconazole (MIC ?256 ?g/ml), voriconazole (MIC ?32 ?g/ml), itraconazole (MIC ?32 ?g/ml), and posaconazole (MIC ?32 ?g/ml), but susceptible to caspofungin (MIC range 0.064 to 0.19 ?g/ml). CONCLUSION: This appears to be the first report on isolation of cholesterol-dependent strains of C. glabrata from a candidemia patient exhibiting resistance to azoles and amphotericin B. Further, the report demonstrates that induction of cholesterol/sterol auxotrophy is associated with resistance to antifungal drugs targeting ergosterol biosynthesis. These observations may have therapeutic implications for the treatment of infections caused by such C. glabrata strains.

Dataset Information

Breakthrough candidemia due to multidrug-resistant Candida glabrata during prophylaxis with a low dose of micafungin.

Publications

Breakthrough candidemia due to multidrug-resistant Candida glabrata during prophylaxis with a low dose of micafungin.

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