{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:09:40Z","timestamp":1790712580020,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,7,20]],"date-time":"2019-07-20T00:00:00Z","timestamp":1563580800000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Pulmocide Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Management of Candida auris infection is difficult as this yeast exhibits resistance to different classes of antifungals, necessitating the development of new antifungals. The aim of this study was to investigate the susceptibility of C. auris to a novel antifungal triazole, PC945, optimized for topical delivery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A collection of 50 clinical isolates was obtained from a tertiary care hospital in North India. Nine isolates from the UK, 10 from a CDC panel (USA) and 3 from the CBS-KNAW culture collection (Japanese and South Korean isolates) were also obtained. MICs (azole endpoint) of PC945 and other triazoles were determined in accordance with CLSI M27 (third edition). Quality control strains were included [Candida parapsilosis (ATCC 22019) and Candida krusei (ATCC 6258)].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seventy-four percent of isolates tested showed reduced susceptibility to fluconazole (\u226564\u2009mg\/L). PC945 (geometric mean MIC\u205f=\u205f0.058\u2009mg\/L) was 7.4-fold and 1.5-fold more potent than voriconazole and posaconazole, respectively (both P\u205f&lt;\u205f0.01). PC945 MIC values correlated with those of voriconazole or posaconazole, and only three isolates were found to be cross-resistant between PC945 and other azoles. ERG11 sequence analysis revealed several mutations, but no correlation could be established with the MIC of PC945. Tentative epidemiological cut-off values (ECOFFs) evaluated by CLSI\u2019s ECOFF Finder (at 99%) with 24\u2009h reading of MICs were 1, 4 and 1\u2009mg\/L for PC945, voriconazole and posaconazole, respectively. MIC values for quality control strains of all triazoles were in the normal ranges.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PC945 was found to be a more potent inhibitor than posaconazole, voriconazole and fluconazole of C. auris isolates collected globally, warranting further laboratory and clinical evaluations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkz280","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T15:11:32Z","timestamp":1560957092000},"page":"2943-2949","source":"Crossref","is-referenced-by-count":44,"title":["In vitro antifungal activity of a novel topical triazole PC945 against emerging yeast Candida auris"],"prefix":"10.1093","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9097-9253","authenticated-orcid":false,"given":"Shivaprakash M","family":"Rudramurthy","sequence":"first","affiliation":[{"name":"Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Colley","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Abdolrasouli","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, North West London Pathology, Imperial College Healthcare NHS Trust, London, UK"},{"name":"National Heart and Lung Institute, Imperial College School of Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jed","family":"Ashman","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manpreet","family":"Dhaliwal","sequence":"additional","affiliation":[{"name":"Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harsimran","family":"Kaur","sequence":"additional","affiliation":[{"name":"Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darius","family":"Armstrong-James","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College School of Medicine, London, UK"},{"name":"Department of Microbiology, Royal Brompton Hospital, Royal Brompton and Harefield NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pete","family":"Strong","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth","family":"Rapeport","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Schelenz","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Royal Brompton Hospital, Royal Brompton and Harefield NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Ito","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1555-3807","authenticated-orcid":false,"given":"Arunaloke","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,19]]},"reference":[{"key":"2019092005514589100_dkz280-B1","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1086\/597108","article-title":"Candida haemulonii and closely related species at 5 university hospitals in Korea: identification, antifungal susceptibility, and clinical features","volume":"48","author":"Kim","year":"2009","journal-title":"Clin Infect Dis"},{"key":"2019092005514589100_dkz280-B2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1348-0421.2008.00083.x","article-title":"Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital","volume":"53","author":"Satoh","year":"2009","journal-title":"Microbiol Immunol"},{"key":"2019092005514589100_dkz280-B3","doi-asserted-by":"crossref","first-page":"e00578","DOI":"10.1002\/mbo3.578","article-title":"Candida auris: a systematic review and meta-analysis of current updates on an emerging multidrug-resistant pathogen","volume":"7","author":"Sekyere","year":"2018","journal-title":"MicrobiologyOpen"},{"key":"2019092005514589100_dkz280-B4","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00134-014-3603-2","article-title":"Incidence, characteristics and outcome of ICU-acquired candidemia in India","volume":"41","author":"Chakrabarti","year":"2015","journal-title":"Intensive Care Med"},{"key":"2019092005514589100_dkz280-B5","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1093\/jac\/dkx034","article-title":"Candida auris candidaemia in Indian ICUs: analysis of risk factors","volume":"72","author":"Rudramurthy","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2019092005514589100_dkz280-B6","doi-asserted-by":"crossref","first-page":"e00189","DOI":"10.1128\/mSphere.00189-16","article-title":"Comparative pathogenicity of United Kingdom isolates of the emerging pathogen Candida auris and other key pathogenic Candida species","volume":"1","author":"Borman","year":"2016","journal-title":"mSphere"},{"key":"2019092005514589100_dkz280-B7","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1093\/mmy\/myw147","article-title":"Isolates of the emerging pathogen Candida auris present in the UK have several geographic origins","volume":"55","author":"Borman","year":"2017","journal-title":"Med Mycol"},{"key":"2019092005514589100_dkz280-B8","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s10096-013-2027-1","article-title":"Multidrug-resistant endemic clonal strain of Candida auris in India","volume":"33","author":"Chowdhary","year":"2014","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2019092005514589100_dkz280-B9","doi-asserted-by":"crossref","DOI":"10.1099\/jmmcr.0.T00018","article-title":"A rare case of breakthrough fungal pericarditis due to fluconazole-resistant Candida auris in a patient with chronic liver disease","volume":"1","author":"Khillan","year":"2014","journal-title":"JMM Case Rep"},{"key":"2019092005514589100_dkz280-B10","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1093\/cid\/cix460","article-title":"Donor-derived transmission of Candida auris during lung transplantation","volume":"65","author":"Azar","year":"2017","journal-title":"Clin Infect Dis"},{"key":"2019092005514589100_dkz280-B11","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13756-016-0132-5","article-title":"First hospital outbreak of the globally emerging Candida auris in a European hospital","volume":"5","author":"Schelenz","year":"2016","journal-title":"Antimicrob Resist Infect Control"},{"key":"2019092005514589100_dkz280-B12","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.jhin.2017.09.009","article-title":"Controlling a possible outbreak of Candida auris infection: lessons learnt from multiple interventions","volume":"97","author":"Biswal","year":"2017","journal-title":"J Hosp Infect"},{"key":"2019092005514589100_dkz280-B13","doi-asserted-by":"crossref","first-page":"e02280","DOI":"10.1128\/AAC.02280-16","article-title":"In vitro and in vivo antifungal profile of a novel and long-acting inhaled azole, PC945, on Aspergillus fumigatus infection","volume":"61","author":"Colley","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2019092005514589100_dkz280-B14","volume-title":"Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts\u2014Third Edition: M27.","year":"2008"},{"key":"2019092005514589100_dkz280-B15","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1093\/jac\/dkx480","article-title":"A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009\u201317) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance","volume":"73","author":"Chowdhary","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2019092005514589100_dkz280-B16","doi-asserted-by":"crossref","first-page":"e01624","DOI":"10.1128\/JCM.01624-18","article-title":"Candida auris clinical isolates from South Korea: identification, antifungal susceptibility, and genotyping","volume":"57","author":"Kwon","year":"2019","journal-title":"J Clin Microbiol"},{"key":"2019092005514589100_dkz280-B17","doi-asserted-by":"crossref","first-page":"e1003633.","DOI":"10.1371\/journal.ppat.1003633","article-title":"Emergence of azole-resistant Aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health","volume":"9","author":"Chowdhary","year":"2013","journal-title":"PLoS Pathog"},{"key":"2019092005514589100_dkz280-B18","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.nmni.2016.07.003","article-title":"Whole genome sequencing of emerging multidrug resistant Candida auris isolates in India demonstrates low genetic variation","volume":"13","author":"Sharma","year":"2016","journal-title":"New Microbes New Infect"},{"key":"2019092005514589100_dkz280-B19","doi-asserted-by":"crossref","first-page":"3139","DOI":"10.1128\/JCM.00319-11","article-title":"First three reported cases of nosocomial fungemia caused by Candida auris","volume":"49","author":"Lee","year":"2011","journal-title":"J Clin Microbiol"},{"key":"2019092005514589100_dkz280-B20","doi-asserted-by":"crossref","first-page":"e00485","DOI":"10.1128\/AAC.00485-17","article-title":"Comparison of EUCAST and CLSI reference microdilution MICs of eight antifungal compounds for Candida auris and associated tentative epidemiological cutoff values","volume":"61","author":"Arendrup","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2019092005514589100_dkz280-B21","first-page":"43.","article-title":"Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris","volume":"7","author":"Rhodes","year":"2018","journal-title":"Emerg Microbes Infect"},{"key":"2019092005514589100_dkz280-B22","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1128\/AAC.05947-11","article-title":"Antibiotic exposure as a risk factor for fluconazole-resistant Candida bloodstream infection","volume":"56","author":"Ben-Ami","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"2019092005514589100_dkz280-B23","doi-asserted-by":"crossref","first-page":"155","DOI":"10.2147\/IDR.S116229","article-title":"Current perspective on emergence, diagnosis and drug resistance in Candida auris","volume":"10","author":"Sarma","year":"2017","journal-title":"Infect Drug Resist"},{"key":"2019092005514589100_dkz280-B24","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3201\/eid2302.161486","article-title":"Multidrug-resistant Candida haemulonii and C. auris, Tel Aviv, Israel","volume":"23","author":"Ben-Ami","year":"2017","journal-title":"Emerg Infect Dis"},{"key":"2019092005514589100_dkz280-B25","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1093\/jac\/dkm330","article-title":"Hepatotoxicity of oral and intravenous voriconazole in relation to cytochrome P450 polymorphisms","volume":"60","author":"Levin","year":"2007","journal-title":"J Antimicrob Chemother"},{"key":"2019092005514589100_dkz280-B26","first-page":"43","article-title":"Update on the optimal use of voriconazole for invasive fungal infections","volume":"4","author":"Lat","year":"2011","journal-title":"Infect Drug Resist"},{"key":"2019092005514589100_dkz280-B27","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1586\/14787210.2015.1102053","article-title":"Voriconazole-associated phototoxic dermatoses and skin cancer","volume":"13","author":"Goyal","year":"2015","journal-title":"Expert Rev Anti Infect Ther"},{"key":"2019092005514589100_dkz280-B28","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1128\/AAC.01657-08","article-title":"Inhaled voriconazole for prevention of invasive pulmonary aspergillosis","volume":"53","author":"Tolman","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"2019092005514589100_dkz280-B29","first-page":"645","article-title":"PC945, a novel inhaled azole for treatment of fungal tracheobronchitis post-lung transplantation: a case report","volume":"8","author":"Pagani","year":"2019","journal-title":"F1000Res"},{"key":"2019092005514589100_dkz280-B30","year":"2018"},{"key":"2019092005514589100_dkz280-B31","year":"2018"},{"key":"2019092005514589100_dkz280-B32","doi-asserted-by":"crossref","first-page":"e02396","DOI":"10.1128\/AAC.02396-16","article-title":"The emerging pathogen Candida auris: growth phenotype, virulence factors, activity of antifungals, and effect of SCY-078, a novel glucan synthesis inhibitor, on growth morphology and biofilm formation","volume":"61","author":"Larkin","year":"2017","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jac\/advance-article-pdf\/doi\/10.1093\/jac\/dkz280\/28964493\/dkz280.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/74\/10\/2943\/30039345\/dkz280.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T05:52:36Z","timestamp":1568958756000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/74\/10\/2943\/5536332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,19]]},"references-count":32,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,7,19]]},"published-print":{"date-parts":[[2019,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkz280","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,10]]},"published":{"date-parts":[[2019,7,19]]}}}