Genetically related micafungin-resistant Candida parapsilosis blood isolates harbouring novel mutation R658G in hotspot 1 of Fks1p: a new challenge?. (11th November 2020)

• Record Type: Journal Article
• Authors: Arastehfar, Amir; Daneshnia, Farnaz; Hilmioglu-Polat, Süleyha; Ilkit, Macit; Yasar, Melike; Polat, Furkan; Metin, Dilek Yeşim; Dokumcu, Ülküm Zafer; Pan, Weihua; Hagen, Ferry; Boekhout, Teun; Perlin, David S; Lass-Flörl, Cornelia
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 76:Number 2(2021)
• Page Start: 418
• Page End: 422
• Publication Date: 2020-11-11
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkaa419
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: Echinocandin resistance rarely occurs in clinical Candida parapsilosis isolates and the underlying mechanism is unknown. Objectives: To determine the prevalence of echinocandin resistance and the underlying mechanism for a large collection of C. parapsilosis blood isolates and to determine whether the echinocandin-resistant isolates were clonally related. Methods: C. parapsilosis blood isolates ( n = 213) were subjected to antifungal susceptibility testing (CLSI M27), for micafungin, anidulafungin, amphotericin B and, if appropriate, caspofungin. Hotspot (HS) 1 and HS2 of FKS1 were sequenced for all isolates ( n = 213) and microsatellite typing was performed for echinocandin-resistant isolates. Results: All isolates were susceptible to amphotericin B and two isolates were intermediate to anidulafungin (MIC = 4 mg/L), while micafungin resistance was noted in four isolates (MIC >8 mg/L); three of which were also fluconazole resistant and therefore were MDR. Interestingly, micafungin-resistant isolates, but not those intermediate to anidulafungin, carried novel mutation R658G in HS1 of Fks1p; three of which also harboured Y132F+K143R in Erg11. The first isolate (MICR1) was recovered in November 2017 from a patient admitted to paediatric gastroenterology who showed therapeutic failure under caspofungin treatment. MICR2–MICR4 were collected during 2018–19 and were recovered from three echinocandin-naive paediatric-surgery patients; the isolates shared the same genotype. Conclusions: Herein, for the first time (to the best of our knowledge), we identified micafungin-resistant C. parapsilosis blood isolates harbouring a novel mutation in HS1 of FKS1, which was likely attributable to in vitro micafungin resistance and in vivo caspofungin therapeutic failure. The acquisition of micafungin-resistant C. parapsilosis isolates in echinocandin-naive patients likely implicates clonal expansion, as supported by the close genetic relatedness of MICR2–MICR4.