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. 2020 Sep 21;64(10):e01001-20.
doi: 10.1128/AAC.01001-20. Print 2020 Sep 21.

First Report of Candidemia Clonal Outbreak Caused by Emerging Fluconazole-Resistant Candida parapsilosis Isolates Harboring Y132F and/or Y132F+K143R in Turkey

Amir Arastehfar #  1 , Farnaz Daneshnia #  2 , Suleyha Hilmioğlu-Polat  3 , Wenjie Fang  4   5 , Melike Yaşar  3 , Furkan Polat  3 , Dilek Yeşim Metin  3 , Petra Rigole  6 , Tom Coenye  6 , Macit Ilkit  7 , Weihua Pan  8   5 , Wanqing Liao  4   5 , Ferry Hagen  2   9 , Markus Kostrzewa  10 , David S Perlin  1 , Cornelia Lass-Flörl  11 , Teun Boekhout  2   12
Affiliations

First Report of Candidemia Clonal Outbreak Caused by Emerging Fluconazole-Resistant Candida parapsilosis Isolates Harboring Y132F and/or Y132F+K143R in Turkey

Amir Arastehfar et al. Antimicrob Agents Chemother. .

Abstract

Clonal outbreaks of fluconazole-resistant (FLZR) Candida parapsilosis isolates have been reported in several countries. Despite its being the second leading cause of candidemia, the azole resistance mechanisms and the clonal expansion of FLZR C. parapsilosis blood isolates have not been reported in Turkey. In this study, we consecutively collected C. parapsilosis blood isolates (n = 225) from the fifth largest hospital in Turkey (2007 to 2019), assessed their azole susceptibility pattern using CLSI M27-A3/S4, and sequenced ERG11 for all and MRR1, TAC1, and UPC2 for a selected number of C. parapsilosis isolates. The typing resolution of two widely used techniques, amplified fragment length polymorphism typing (AFLP) and microsatellite typing (MST), and the biofilm production of FLZR isolates with and without Y132F were compared. Approximately 27% of isolates were FLZR (60/225), among which 90% (54/60) harbored known mutations in Erg11, including Y132F (24/60) and Y132F+K143R (19/60). Several mutations specific to FLZR isolates were found in MRR1, TAC1, and UPC2 AFLP grouped isolates into two clusters, while MST revealed several clusters. The majority of Y132F/Y132F+K143R isolates grouped in clonal clusters, which significantly expanded throughout 2007 to 2019 in neonatal wards. Candida parapsilosis isolates carrying Y132F were associated with significantly higher mortality and less biofilm production than other FLZR isolates. Collectively, we documented the first outbreak of FLZR C. parapsilosis blood isolates in Turkey. The MRR1, TAC1, and UPC2 mutations exclusively found in FLZR isolates establishes a basis for future studies, which will potentially broaden our knowledge of FLZR mechanisms in C. parapsilosis MST should be a preferred method for clonal analysis of C. parapsilosis isolates in outbreak scenarios.

Keywords: Candida; Candida parapsilosis; drug resistance mechanisms; fluconazole.

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Figures

FIG 1
FIG 1
Frequency of mutations in ERG11 responsible for resistance and azole use for prophylaxis or treatment in 2007 to 2019.
FIG 2
FIG 2
Minimum spanning tree obtained by MST of 91 isolates with azole resistance (A) and all study isolates (B). Isolates carrying Y132F and Y132F+K143R formed distinct clusters. SDD, susceptible (dose dependent).
See this image and copyright information in PMC

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