{"doi":"10.1128/aac.00238-18","title":"Understanding Echinocandin Resistance in the Emerging Pathogen Candida auris","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Candida auris</jats:named-content>\n            has simultaneously emerged on five continents as a fungal pathogen causing nosocomial outbreaks. The challenges in the treatment of\n            <jats:named-content content-type=\"genus-species\">C. auris</jats:named-content>\n            infections are the variable antifungal susceptibility profiles among clinical isolates and the development of resistance to single or multiple classes of available antifungal drugs. Here, the\n            <jats:italic>in vitro</jats:italic>\n            susceptibility to echinocandin antifungal drugs was determined and\n            <jats:italic>FKS1</jats:italic>\n            sequencing was performed on 106\n            <jats:named-content content-type=\"genus-species\">C. auris</jats:named-content>\n            clinical isolates. Four isolates were identified to be resistant to all tested echinocandins (MIC ≥ 4 mg/liter) and harbored an S639F mutation in\n            <jats:italic>FKS1</jats:italic>\n            hot spot region 1. All remaining isolates were\n            <jats:italic>FKS1</jats:italic>\n            wild type (WT) and echinocandin susceptible, with micafungin being the most potent echinocandin (MIC\n            <jats:sub>50</jats:sub>\n            = 0.125 mg/liter). Antifungal susceptibility testing with caspofungin was challenging due to the fact that all\n            <jats:italic>FKS1</jats:italic>\n            WT isolates exhibited an Eagle effect (also known as the paradoxical growth effect), which occurred at various intensities. To assess whether the Eagle effect resulted in pharmacodynamic resistance, 8 representative isolates were evaluated for their\n            <jats:italic>in vivo</jats:italic>\n            drug response in a murine model of invasive candidiasis. All isolates were susceptible to caspofungin at a human therapeutic dose, except for those harboring the S639F mutation. The data suggest that only isolates carrying mutations in\n            <jats:italic>FKS1</jats:italic>\n            are echinocandin resistant and that routine\n            <jats:italic>in vitro</jats:italic>\n            testing of\n            <jats:named-content content-type=\"genus-species\">C. auris</jats:named-content>\n            isolates for susceptibility to caspofungin by the broth microdilution method should be viewed cautiously or avoided.\n          </jats:p>","journal":"Antimicrobial Agents and Chemotherapy","year":2018,"id":593912,"datarank":0.8306001400527806,"base_score":5.537334267018537,"endowment":5.537334267018537,"self_citation_contribution":0.8306001400527806,"citation_network_contribution":0.0,"self_endowment_contribution":0.8306001400527806,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":253,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":571211,"name":"Annie Lee","orcid":"0000-0003-3726-6024","position":1,"is_corresponding":false},{"id":277904,"name":"Steven Park","orcid":"0000-0001-5674-6408","position":2,"is_corresponding":false},{"id":1520119,"name":"Indira Berrio","orcid":null,"position":3,"is_corresponding":false},{"id":355933,"name":"Anuradha Chowdhary","orcid":"0000-0002-2028-7462","position":4,"is_corresponding":false},{"id":832294,"name":"Yanan Zhao","orcid":"0000-0002-6634-2949","position":5,"is_corresponding":false},{"id":336885,"name":"David S. Perlin","orcid":"0000-0002-1268-5524","position":6,"is_corresponding":false},{"id":808269,"name":"Milena Kordalewska","orcid":"0000-0001-8479-0721","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Understanding Echinocandin Resistance in the Emerging Pathogen Candida auris","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Candida auris</jats:named-content>\n            has simultaneously emerged on five continents as a fungal pathogen causing nosocomial outbreaks. The challenges in the treatment of\n            <jats:named-content content-type=\"genus-species\">C. auris</jats:named-content>\n            infections are the variable antifungal susceptibility profiles among clinical isolates and the development of resistance to single or multiple classes of available antifungal drugs. Here, the\n            <jats:italic>in vitro</jats:italic>\n            susceptibility to echinocandin antifungal drugs was determined and\n            <jats:italic>FKS1</jats:italic>\n            sequencing was performed on 106\n            <jats:named-content content-type=\"genus-species\">C. auris</jats:named-content>\n            clinical isolates. Four isolates were identified to be resistant to all tested echinocandins (MIC ≥ 4 mg/liter) and harbored an S639F mutation in\n            <jats:italic>FKS1</jats:italic>\n            hot spot region 1. All remaining isolates were\n            <jats:italic>FKS1</jats:italic>\n            wild type (WT) and echinocandin susceptible, with micafungin being the most potent echinocandin (MIC\n            <jats:sub>50</jats:sub>\n            = 0.125 mg/liter). Antifungal susceptibility testing with caspofungin was challenging due to the fact that all\n            <jats:italic>FKS1</jats:italic>\n            WT isolates exhibited an Eagle effect (also known as the paradoxical growth effect), which occurred at various intensities. To assess whether the Eagle effect resulted in pharmacodynamic resistance, 8 representative isolates were evaluated for their\n            <jats:italic>in vivo</jats:italic>\n            drug response in a murine model of invasive candidiasis. All isolates were susceptible to caspofungin at a human therapeutic dose, except for those harboring the S639F mutation. The data suggest that only isolates carrying mutations in\n            <jats:italic>FKS1</jats:italic>\n            are echinocandin resistant and that routine\n            <jats:italic>in vitro</jats:italic>\n            testing of\n            <jats:named-content content-type=\"genus-species\">C. auris</jats:named-content>\n            isolates for susceptibility to caspofungin by the broth microdilution method should be viewed cautiously or avoided.\n          </jats:p>","is_dataset_classified":null,"base_score":5.537334267018537,"endowment":5.537334267018537,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29632013","pmcid":"PMC5971591","openalex_id":"https://openalex.org/W2795884050","authors":[],"funders":[{"funder_name":"HHS | National Institutes of Health","grant_id":"AI109025","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI109025","title":null},{"funder_name":"Astellas Pharma US","grant_id":"","title":null}],"total_grants":3,"fwci":16.958,"citation_percentile":0.99592224,"influential_citations":0,"citation_trend":[{"year":2018,"count":10},{"year":2019,"count":26},{"year":2020,"count":40},{"year":2021,"count":43},{"year":2022,"count":32},{"year":2023,"count":30},{"year":2024,"count":26},{"year":2025,"count":25},{"year":2026,"count":20}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://aac.asm.org/content/aac/62/6/e00238-18.full.pdf","host_type":"journal"},{"url":"https://aac.asm.org/content/aac/62/6/e00238-18.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/AAC.00238-18","host_type":"publisher"},{"url":"https://doi.org/10.1128/aac.00238-18","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29632013","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5971591","host_type":"repository"}],"fields_of_study":["Antifungal resistance and susceptibility","Fungal Infections and Studies","Respiratory and Cough-Related Research"],"mesh_terms":["Animals","Antifungal Agents","Candida","Candidiasis","Cross Infection","Female","Glucosyltransferases","Humans","Mice, Inbred BALB C","Microbial Sensitivity Tests","Drug Resistance, Fungal","Mice","Echinocandins","Candidiasis, Invasive"],"keywords":["Candida auris","Echinocandin","Fungal pathogen","Echinocandins","Microbiology","Pathogen","Biology","Drug resistance","Antifungal","Medicine","Fluconazole","Caspofungin","Candida","Susceptibility","Micafungin","Antifungal Susceptibility Testing","Anidulafungin","Antifungal Resistance"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"refseq"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T12:46:42.206193Z","pmid":null,"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":[]}