{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T22:35:30Z","timestamp":1788474930775,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013238","name":"Siriraj Research Fund","doi-asserted-by":"publisher","award":["R016333035"],"award-info":[{"award-number":["R016333035"]}],"id":[{"id":"10.13039\/501100013238","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>In recent decades, an epidemiological shift has been observed from Candida infections to non-albicans species and resistance to azoles. We investigated the associated factors and molecular mechanisms of azole-resistant blood isolates of C. tropicalis. Full-length sequencing of the ERG11 gene and quantitative real-time RT-PCR for the ERG11, MDR1, and CDR1 genes were performed. Male sex (odds ratio, 0.38), leukemia (odds ratio 3.15), and recent administration of azole (odds ratio 10.56) were associated with isolates resistant to azole. ERG11 mutations were found in 83% of resistant isolates, with A395T as the most common mutation (53%). There were no statistically significant differences in the expression of the ERG11, MDR1, and CDR1 genes between the groups resistant and susceptible to azole. The prevalence of azole-resistant isolates was higher than the usage of antifungal drugs, suggesting the possibility of environmental transmission in the healthcare setting. The unknown mechanism of the other 17% of the resistant isolates remains to be further investigated.<\/jats:p>","DOI":"10.3390\/jof8100983","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T22:36:44Z","timestamp":1663713404000},"page":"983","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Risk Factors and Mechanisms of Azole Resistance of Candida tropicalis Blood Isolates in Thailand: A Retrospective Cohort Study"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2925-9644","authenticated-orcid":false,"given":"Teera","family":"Leepattarakit","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9078-0650","authenticated-orcid":false,"given":"Orawan","family":"Tulyaprawat","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5162-5498","authenticated-orcid":false,"given":"Popchai","family":"Ngamskulrungroj","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. (2017). Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision. J. Fungi, 3.","DOI":"10.3390\/jof3040057"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.1093\/ofid\/ofy358","article-title":"Twenty Years of the SENTRY Antifungal Surveillance Program: Results for Candida Species from 1997\u20132016","volume":"6","author":"Pfaller","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Boonsilp, S., Homkaew, A., Phumisantiphong, U., Nutalai, D., and Wongsuk, T. (2021). Species Distribution, Antifungal Susceptibility, and Molecular Epidemiology of Candida Species Causing Candidemia in a Tertiary Care Hospital in Bangkok, Thailand. J. Fungi, 7.","DOI":"10.3390\/jof7070577"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ngamchokwathana, C., Chongtrakool, P., Waesamaae, A., and Chayakulkeeree, M. (2021). Risk Factors and Outcomes of Non-albicans Candida Bloodstream Infection in Patients with Candidemia at Siriraj Hospital\u2014Thailand\u2019s Largest National Tertiary Referral Hospital. J. Fungi, 7.","DOI":"10.3390\/jof7040269"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e19494","DOI":"10.1097\/MD.0000000000019494","article-title":"A multicenter retrospective analysis of the antifungal susceptibility patterns of Candida species and the predictive factors of mortality in South Korean patients with candidemia","volume":"99","author":"Jung","year":"2020","journal-title":"Medicine"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wang, Q., Tang, D., Tang, K., Guo, J., Huang, Y., and Li, C. (2020). Multilocus Sequence Typing Reveals Clonality of Fluconazole-Nonsusceptible Candida tropicalis: A Study from Wuhan to the Global. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.554249"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S139","DOI":"10.1093\/infdis\/jiz573","article-title":"Distribution and Antifungal Susceptibility of Candida Species Causing Candidemia in China: An Update From the CHIF-NET Study","volume":"221","author":"Xiao","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/myc.13429","article-title":"EQUAL Candida score, an effective tool for predicting the outcomes of Candida tropicalis candidaemia: A retrospective cohort study","volume":"65","author":"Leepattarakit","year":"2022","journal-title":"Mycoses"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"110","DOI":"10.4103\/ijmm.IJMM_20_112","article-title":"Candidaemia in a tertiary care centre of developing country: Monitoring possible change in spectrum of agents and antifungal susceptibility","volume":"38","author":"Kaur","year":"2020","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s11046-021-00580-y","article-title":"Virulence Factors and Azole-Resistant Mechanism of Candida tropicalis Isolated from Candidemia","volume":"186","author":"Sasani","year":"2021","journal-title":"Mycopathologia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1093\/mmy\/myv114","article-title":"Antifungal susceptibility of invasive Candida bloodstream isolates from the Asia-Pacific region","volume":"54","author":"Tan","year":"2016","journal-title":"Med. Mycol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Aldardeer, N.F., Albar, H., Al-Attas, M., Eldali, A., Qutub, M., Hassanien, A., and Alraddadi, B. (2020). Antifungal resistance in patients with Candidaemia: A retrospective cohort study. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-019-4710-z"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"ofac447","DOI":"10.1093\/ofid\/ofac447","article-title":"Creation and Internal Validation of a Clinical Predictive Model for Fluconazole Resistance in Patients with Candida Bloodstream Infection","volume":"9","author":"Rauseo","year":"2022","journal-title":"Open Forum Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.3389\/fmicb.2016.02173","article-title":"Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species","volume":"7","author":"Whaley","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.cmi.2018.11.007","article-title":"Molecular mechanisms of azole resistance in Candida tropicalis isolates causing invasive candidiasis in China","volume":"25","author":"Fan","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Teo, J.Q., Lee, S.J., Tan, A.L., Lim, R.S., Cai, Y., Lim, T.P., and Kwa, A.L. (2019). Molecular mechanisms of azole resistance in Candida bloodstream isolates. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-3672-5"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J. Chronic Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1093\/cid\/cit278","article-title":"A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2013 Recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)a","volume":"57","author":"Baron","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"684.e1-9","DOI":"10.1016\/j.cmi.2015.02.029","article-title":"A simple prediction score for estimating the risk of candidaemia caused by fluconazole non-susceptible strains","volume":"21","author":"Cuervo","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_21","unstructured":"CLSI (2020). Performance Standards for Antifungal Susceptibility Testing of Yeasts, Clinical and Laboratory Standards Institute. [2nd ed.]."},{"key":"ref_22","unstructured":"CLSI (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard\u2014Third Edition, Clinical and Laboratory Standards Institute."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1111\/1567-1364.12178","article-title":"Multilocus sequence typing (MLST) and M13 PCR fingerprinting revealed heterogeneity amongst Cryptococcus species obtained from Italian veterinary isolates","volume":"14","author":"Danesi","year":"2014","journal-title":"FEMS Yeast Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.jgar.2020.04.018","article-title":"Dynamics of in vitro development of azole resistance in Candida tropicalis","volume":"22","author":"Paul","year":"2020","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1093\/aje\/kwk052","article-title":"Relaxing the Rule of Ten Events per Variable in Logistic and Cox Regression","volume":"165","author":"Vittinghoff","year":"2006","journal-title":"Am. J. Epidemiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"106592","DOI":"10.1016\/j.ijantimicag.2022.106592","article-title":"Genetic relatedness among azole-resistant Candida tropicalis clinical strains in Taiwan from 2014 to 2018","volume":"59","author":"Zhou","year":"2022","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Thomaz, D.Y., de Almeida, J.N., Sejas, O.N.E., Del Negro, G.M.B., Carvalho, G.O.M.H., Gimenes, V.M.F., de Souza, M.E.B., Arastehfar, A., Camargo, C.H., and Motta, A.L. (2021). Environmental Clonal Spread of Azole-Resistant Candida parapsilosis with Erg11-Y132F Mutation Causing a Large Candidemia Outbreak in a Brazilian Cancer Referral Center. J. Fungi, 7.","DOI":"10.3390\/jof7040259"},{"key":"ref_29","first-page":"3221","article-title":"European guidelines for primary antifungal prophylaxis in adult haematology patients: Summary of the updated recommendations from the European Conference on Infections in Leukaemia","volume":"73","author":"Maertens","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s12275-016-5628-4","article-title":"The development of fluconazole resistance in Candida albicans\u2014An example of microevolution of a fungal pathogen","volume":"54","year":"2016","journal-title":"J. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/1469-0691.12039","article-title":"ESCMID* *This guideline was presented in part at ECCMID 2011. European Society for Clinical Microbiology and Infectious Diseases. guideline for the diagnosis and management of Candida diseases 2012: Non-neutropenic adult patients","volume":"18","author":"Cornely","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1093\/jac\/dks481","article-title":"Mechanisms of azole resistance in 52 clinical isolates of Candida tropicalis in China","volume":"68","author":"Jiang","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_34","first-page":"988","article-title":"Pan-azole-resistant Candida tropicalis carrying homozygous erg11 mutations at position K143R: A new emerging superbug?","volume":"72","author":"Xisto","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4769","DOI":"10.1128\/AAC.00477-13","article-title":"Candida tropicalis antifungal cross-resistance is related to different azole target (Erg11p) modifications","volume":"57","author":"Forastiero","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s11046-016-0050-3","article-title":"The Role of UPC2 Gene in Azole-Resistant Candida tropicalis","volume":"181","author":"Jiang","year":"2016","journal-title":"Mycopathologia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"302.e5","DOI":"10.1016\/j.cmi.2021.10.004","article-title":"Azole and echinocandin resistance mechanisms and genotyping of Candida tropicalis in Japan: Cross-boundary dissemination and animal\u2013human transmission of C. tropicalis infection","volume":"28","author":"Khalifa","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Paul, S., Shaw, D., Joshi, H., Singh, S., Chakrabarti, A., Rudramurthy, S.M., and Ghosh, A.K. (2022). Mechanisms of azole antifungal resistance in clinical isolates of Candida tropicalis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0269721"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4608","DOI":"10.1128\/AAC.49.11.4608-4615.2005","article-title":"Mechanisms of azole resistance in a clinical isolate of Candida tropicalis","volume":"49","author":"Vandeputte","year":"2005","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/8\/10\/983\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:34:56Z","timestamp":1760142896000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/8\/10\/983"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,20]]},"references-count":39,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["jof8100983"],"URL":"https:\/\/doi.org\/10.3390\/jof8100983","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,20]]}}}