{"doi":"10.1111/myc.13296","title":"Species distribution, azole resistance and related molecular mechanisms in invasive <i>Candida parapsilosis</i> complex isolates: Increase in fluconazole resistance in 21 years","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p><jats:italic>Candida parapsilosis</jats:italic> complex consists of three species, the prevalence and geographical distribution of which might vary. Increasing rates of fluconazole resistance among <jats:italic>C. parapsilosis</jats:italic> complex were reported from various centres.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>Aim of this study was to identify invasive <jats:italic>C. parapsilosis</jats:italic> complex strains up to species level, explore rates and molecular mechanisms of azole resistance and analyse temporal changes at a single centre.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Isolates from blood cultures from 1997 to 2017 were included. Species were identified using RFLP of the <jats:italic>SADH</jats:italic> gene and confirmed with <jats:italic>ITS</jats:italic> sequencing when needed. In vitro susceptibility to fluconazole, voriconazole and posaconazole was tested and evaluated using EUCAST guidelines. Sequences of <jats:italic>ERG11</jats:italic> and <jats:italic>MRR1</jats:italic> genes were analysed for fluconazole non‐susceptible isolates.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 283 isolates from 181 patients were tested for azole susceptibility. All were <jats:italic>C. parapsilosis</jats:italic> sensu <jats:italic>stricto</jats:italic>, except one <jats:italic>C. orthopsilosis</jats:italic>. All three azoles were effective against 213 of the isolates from 135 patients, including one <jats:italic>C. orthopsilosis</jats:italic>. Fluconazole resistance was 13.3% (24/181 patients). While the first fluconazole‐resistant isolates were detected in 2004, increase was evident after 2011. In <jats:italic>ERG11</jats:italic>, Y132F mutation was the most common among fluconazole non‐susceptible isolates (71.7%), followed by G458S (10.9%) and D421N (4.3%). In MRR1, R405K (56.5%) and G927C (8.7%) were detected. However, association of these mutations to azole resistance is yet to be investigated.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Rising azole resistance rates in <jats:italic>C. parapsilosis</jats:italic> sensu <jats:italic>stricto</jats:italic> isolates particularly after 2011 were of concern. The well‐known Y132F mutation was the predominant mechanism of azole resistance while accompanied with other genetic mutations.</jats:p></jats:sec>","journal":"Mycoses","year":2021,"id":644090,"datarank":0.5416376868966337,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.0,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"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":1676207,"name":"Sevtap Arikan‐Akdagli","orcid":null,"position":1,"is_corresponding":false},{"id":1676208,"name":"Dolunay Gülmez","orcid":"0000-0001-9021-0439","position":2,"is_corresponding":false},{"id":1676206,"name":"Selay Demirci‐Duarte","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Species distribution, azole resistance and related molecular mechanisms in invasive <i>Candida parapsilosis</i> complex isolates: Increase in fluconazole resistance in 21 years","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p><jats:italic>Candida parapsilosis</jats:italic> complex consists of three species, the prevalence and geographical distribution of which might vary. Increasing rates of fluconazole resistance among <jats:italic>C. parapsilosis</jats:italic> complex were reported from various centres.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>Aim of this study was to identify invasive <jats:italic>C. parapsilosis</jats:italic> complex strains up to species level, explore rates and molecular mechanisms of azole resistance and analyse temporal changes at a single centre.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Isolates from blood cultures from 1997 to 2017 were included. Species were identified using RFLP of the <jats:italic>SADH</jats:italic> gene and confirmed with <jats:italic>ITS</jats:italic> sequencing when needed. In vitro susceptibility to fluconazole, voriconazole and posaconazole was tested and evaluated using EUCAST guidelines. Sequences of <jats:italic>ERG11</jats:italic> and <jats:italic>MRR1</jats:italic> genes were analysed for fluconazole non‐susceptible isolates.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 283 isolates from 181 patients were tested for azole susceptibility. All were <jats:italic>C. parapsilosis</jats:italic> sensu <jats:italic>stricto</jats:italic>, except one <jats:italic>C. orthopsilosis</jats:italic>. All three azoles were effective against 213 of the isolates from 135 patients, including one <jats:italic>C. orthopsilosis</jats:italic>. Fluconazole resistance was 13.3% (24/181 patients). While the first fluconazole‐resistant isolates were detected in 2004, increase was evident after 2011. In <jats:italic>ERG11</jats:italic>, Y132F mutation was the most common among fluconazole non‐susceptible isolates (71.7%), followed by G458S (10.9%) and D421N (4.3%). In MRR1, R405K (56.5%) and G927C (8.7%) were detected. However, association of these mutations to azole resistance is yet to be investigated.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Rising azole resistance rates in <jats:italic>C. parapsilosis</jats:italic> sensu <jats:italic>stricto</jats:italic> isolates particularly after 2011 were of concern. The well‐known Y132F mutation was the predominant mechanism of azole resistance while accompanied with other genetic mutations.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33934400","pmcid":null,"openalex_id":"https://openalex.org/W3157614724","authors":[],"funders":[{"funder_name":"Hacettepe University Scientific Research Projects Coordination Unit","grant_id":"TSA-2018-17112","title":null}],"total_grants":1,"fwci":1.7962,"citation_percentile":0.87776071,"influential_citations":0,"citation_trend":[{"year":2021,"count":3},{"year":2022,"count":9},{"year":2023,"count":9},{"year":2024,"count":8},{"year":2025,"count":7}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/myc.13296","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1111/myc.13296","host_type":"publisher"},{"url":"https://doi.org/10.1111/myc.13296","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33934400","host_type":"repository"}],"fields_of_study":["Antifungal resistance and susceptibility","Nail Diseases and Treatments","Fungal Infections and Studies","Amino Acid Substitution","Antifungal Agents","Candida parapsilosis","Candidemia","Candidiasis","Drug Resistance, Fungal","Fluconazole","Humans","Microbial Sensitivity Tests","Polymorphism, Single Nucleotide","Tertiary Care Centers","Time Factors","Turkey"],"mesh_terms":["Candida parapsilosis","Antifungal Agents","Candidiasis","Humans","Microbial Sensitivity Tests","Time Factors","Turkey","Fluconazole","Amino Acid Substitution","Polymorphism, Single Nucleotide","Drug Resistance, Fungal","Candidemia","Tertiary Care Centers"],"keywords":["Fluconazole","Posaconazole","Azole","Biology","Voriconazole","Microbiology","Candida parapsilosis","Drug resistance","Antifungal","epidemiology","Candidemia","Fluconazole Resistance","Erg11","Mrr1"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-08T22:46:37.790137Z","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":[]}