ArticleThe Journal of antimicrobial chemotherapy2023
Whole-genome sequencing confirms a persistent candidaemia clonal outbreak due to multidrug-resistant Candida parapsilosis.
Article in The Journal of antimicrobial chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Profound cell wall remodeling inMicrobiology spectrum · 2026Article
- Emerging antifungal resistance in Candida parapsilosis: the end of the innocence.npj antimicrobials and resistance · 2025Review
- Epidemiological Characteristics and Mortality Predictors of Candidemia Due toJournal of fungi (Basel, Switzerland) · 2025Article
- Recent Systemic Antifungal Exposure and Nonsusceptible Candida in Hospitalized Patients, South Africa, 2012-2017.Emerging infectious diseases · 2025Article
- Candidemia: An Update on Epidemiology, Risk Factors, Diagnosis, Susceptibility, and Treatment.Pathogens (Basel, Switzerland) · 2025Review
- Article
- Heterogeneity ofMicrobiology spectrum · 2025Article
- Genomics insights of candidiasis: mechanisms of pathogenicity and drug resistance.Frontiers in microbiology · 2025Review
- Emerging fluconazole-resistantFrontiers in microbiology · 2025Article
- Threats from theMicrobiology and molecular biology reviews : MMBR · 2024Review
- Evaluation of outbreak persistence caused by multidrug-resistant and echinocandin-resistantEmerging microbes & infections · 2024Article
- Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease.Clinical microbiology reviews · 2024Review
- Precise genome editing underlines the distinct contributions of mutations inAntimicrobial agents and chemotherapy · 2024Article
- Invasive candidiasis.Nature reviews. Disease primers · 2024Review
- Review
- First Canadian report of transmission of fluconazole-resistantJournal of clinical microbiology · 2024Article
- In Vitro Susceptibility Tests in the Context of Antifungal Resistance: Beyond Minimum Inhibitory Concentration inJournal of fungi (Basel, Switzerland) · 2023Review
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Authors and funding
13 authors.
Funding
Abstract
objectivesAlthough 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.
methodsWGS 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.
resultsFluconazole 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.
conclusionsOur 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.
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