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  • Species distribution and susceptibility profile to fluconazole, voriconazole and MXP-4509 of 551 clinical yeast isolates from a Romanian multi-centre study.

Species distribution and susceptibility profile to fluconazole, voriconazole and MXP-4509 of 551 clinical yeast isolates from a Romanian multi-centre study.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology (2014-09-17)
B Minea, V Nastasa, R F Moraru, A Kolecka, M M Flonta, I Marincu, A Man, F Toma, M Lupse, B Doroftei, N Marangoci, M Pinteala, T Boekhout, M Mares
ABSTRACT

This is the first multi-centre study regarding yeast infections in Romania. The aim was to determine the aetiological spectrum and susceptibility pattern to fluconazole, voriconazole and the novel compound MXP-4509. The 551 isolates were identified using routine laboratory methods, matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and DNA sequence analysis. Susceptibility testing was performed using the European Committee for Antimicrobial Susceptibility Testing (EUCAST) method and breakpoints. The yeasts originated from superficial infections (SUP, 51.5 %), bloodstream infections (BSI, 31.6 %) and deep-seated infections (DEEP, 16.9 %), from patients of all ages. Nine genera and 30 species were identified. The 20 Candida species accounted for 94.6 % of all isolates. C. albicans was the overall leading pathogen (50.5 %). Lodderomyces elongisporus is reported for the first time as a fungaemia cause in Europe. C. glabrata and Saccharomyces cerevisiae, as well as the non-Candida spp. and non-albicans Candida spp. groups, showed decreased fluconazole susceptibility (<75 %). The overall fluconazole resistance was 10.2 %. C. krusei accounted for 27 of the 56 fluconazole-resistant isolates. The overall voriconazole resistance was 2.5 % and was due mainly to C. glabrata and C. tropicalis isolates. Fluconazole resistance rates for the three categories of infection were similar to the overall value; voriconazole resistance rates differed: 4 % for BSI, 3.2 % for DEEP and 1.4 % for SUP. The antifungal activity of MXP-4509 was superior to voriconazole against C. glabrata and many fluconazole-resistant isolates. There was a large percentage of non-albicans Candida isolates. A large part of the high fluconazole resistance was not acquired but intrinsic, resulting from the high percentage of C. krusei.

MATERIALS
Product Number
Brand
Product Description

Fluconazole for peak identification, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
α-Cyano-4-hydroxycinnamic acid, 99%
Supelco
α-Cyano-4-hydroxycinnamic acid, suitable for matrix substance for MALDI-MS, ≥99.0% (HPLC)
Sigma-Aldrich
α-Cyano-4-hydroxycinnamic acid, suitable for MALDI-TOF MS
Sigma-Aldrich
α-Cyano-4-hydroxycinnamic acid, 97%
Sigma-Aldrich
α-Cyano-4-hydroxycinnamic acid, ≥98% (TLC), powder
Sigma-Aldrich
α-Cyano-4-hydroxycinnamic acid, suitable for matrix substance for MALDI-MS, Ultra pure
Supelco
Fluconazole, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Fluconazole, ≥98% (HPLC), powder
Supelco
Voriconazole, VETRANAL®, analytical standard
USP
Fluconazole, United States Pharmacopeia (USP) Reference Standard
Fluconazole, European Pharmacopoeia (EP) Reference Standard
Voriconazole, European Pharmacopoeia (EP) Reference Standard