Whole-genome sequencing confirms a persistent candidaemia clonal outbreak due to multidrug-resistant Candida parapsilosis

Farnaz Daneshnia, Süleyha Hilmioğlu-Polat, Macit Ilkit, Diego Fuentes, Lisa Lombardi, Ulrike Binder, Jakob Scheler, Ferry Hagen, Michael K Mansour, Geraldine Butler, Cornelia Lass-Flörl, Toni Gabaldon, Amir Arastehfar

Research output: Contribution to journal/periodicalArticleScientificpeer-review

1 Citation (Scopus)

Abstract

OBJECTIVES: Although perceived as a rare clinical entity, recent studies have noted the emergence of MDR C. parapsilosis (MDR-Cp) isolates from single patients (resistant to both azole and echinocandins). We previously reported a case series of MDR-Cp isolates carrying a novel FKS1R658G mutation. Herein, we identified an echinocandin-naive patient infected with MDR-Cp a few months after the previously described isolates. WGS and CRISPR-Cas9 editing were used to explore the origin of the new MDR-Cp isolates, and to determine if the novel mutation confers echinocandin resistance.

METHODS: WGS was applied to assess the clonality of these isolates and CRISPR-Cas9 editing and a Galleria mellonella model were used to examine whether FKS1R658G confers echinocandin resistance.

RESULTS: Fluconazole treatment failed, and the patient was successfully treated with liposomal amphotericin B (LAMB). WGS proved that all historical and novel MDR-Cp strains were clonal and distant from the fluconazole-resistant outbreak cluster in the same hospital. CRISPR-Cas9 editing and G. mellonella virulence assays confirmed that FKS1R658G confers echinocandin resistance in vitro and in vivo. Interestingly, the FKS1R658G mutant showed a very modest fitness cost compared with the parental WT strain, consistent with the persistence of the MDR-Cp cluster in our hospital.

CONCLUSIONS: Our study showcases the emergence of MDR-Cp isolates as a novel threat in clinical settings, which undermines the efficacy of the two most widely used antifungal drugs against candidiasis, leaving only LAMB as a last resort. Additionally, surveillance studies and WGS are warranted to effectively establish infection control and antifungal stewardship strategies.

Original languageEnglish
Pages (from-to)1488-1494
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume78
Issue number6
DOIs
Publication statusPublished - 01 Jun 2023

Keywords

  • Antifungal Agents/pharmacology
  • Candida parapsilosis/genetics
  • Fluconazole/pharmacology
  • Drug Resistance, Fungal
  • Echinocandins/pharmacology
  • Candidemia/drug therapy
  • Microbial Sensitivity Tests

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