{"doi":"10.1093/jac/dkad112","title":"Whole-genome sequencing confirms a persistent candidaemia clonal outbreak due to multidrug-resistant <i>Candida parapsilosis</i>","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.","journal":"Journal of Antimicrobial Chemotherapy","year":2023,"id":333235,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":460958,"name":"Süleyha Hilmioğlu Polat","orcid":"0000-0001-8850-2715","position":1,"is_corresponding":false},{"id":235821,"name":"Macit İlkit","orcid":"0000-0002-1174-4182","position":2,"is_corresponding":false},{"id":884924,"name":"Diego Fuentes","orcid":"0000-0002-9977-6786","position":3,"is_corresponding":false},{"id":621518,"name":"Lisa Lombardi","orcid":"0000-0002-2522-1278","position":4,"is_corresponding":false},{"id":1060490,"name":"Ulrike Binder","orcid":"0000-0002-2160-2903","position":5,"is_corresponding":false},{"id":1061069,"name":"Jakob Scheler","orcid":null,"position":6,"is_corresponding":false},{"id":460956,"name":"Ferry Hagen","orcid":"0000-0002-5622-1916","position":7,"is_corresponding":false},{"id":89098,"name":"Michael K. Mansour","orcid":"0000-0001-8892-8695","position":8,"is_corresponding":false},{"id":91979,"name":"Geraldine Butler","orcid":"0000-0002-1770-5301","position":9,"is_corresponding":false},{"id":235822,"name":"Cornelia Lass‐Flörl","orcid":"0000-0002-2946-7785","position":10,"is_corresponding":false},{"id":30341,"name":"Toni Gabaldón","orcid":"0000-0003-0019-1735","position":11,"is_corresponding":false},{"id":235816,"name":"Amir Arastehfar","orcid":"0000-0002-4361-4841","position":12,"is_corresponding":false},{"id":260363,"name":"Farnaz Daneshnia","orcid":"0000-0002-8782-2036","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-19T01:09:39.719497Z","pmid":"37100456","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}