{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:17:40Z","timestamp":1787170660214,"version":"build-2736575974"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T00:00:00Z","timestamp":1564444800000},"content-version":"vor","delay-in-days":0,"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>The growing emergence of azole-resistant Aspergillus fumigatus strains worldwide is a major concern for current systemic antifungal treatment. Here we report antifungal activities of a novel inhaled triazole, PC1244, against a collection of multi-azole-resistant A. fumigatus strains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MICs of PC1244 were determined for A. fumigatus carrying TR34\/L98H (n\u205f=\u205f81), TR46\/Y121F\/T289A (n\u205f=\u205f24), M220 (n\u205f=\u205f6), G54 (n\u205f=\u205f11), TR53 (n\u205f=\u205f1), TR463\/Y121F\/T289A (n\u205f=\u205f2), G448S (n\u205f=\u205f1), G432C (n\u205f=\u205f1) and P216S (n\u205f=\u205f1) resistance alleles originating from either India, the Netherlands or France. The effects of PC1244 were confirmed in an in vitro model of the human alveolus and in vivo in temporarily neutropenic, immunocompromised mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PC1244 exhibited potent inhibition [geometric mean MIC (range), 1.0\u2009mg\/L (0.125 to &gt;8\u2009mg\/L)] of growth of A. fumigatus strains carrying cyp51A gene mutations, showing much greater potency than voriconazole [15\u2009mg\/L (0.5 to &gt;16\u2009mg\/L)], and an effect similar to those on other azole-susceptible Aspergillus spp. (Aspergillus flavus, Aspergillus terreus, Aspergillus tubingensis, Aspergillus nidulans, Aspergillus niger, Aspergillus nomius, Aspergillus tamarii) (0.18\u20131\u2009mg\/L). In TR34\/L98H and TR46\/Y121F\/T289A A. fumigatus-infected in vitro human alveolus models, PC1244 achieved superior inhibition (IC50, 0.25 and 0.34\u2009mg\/L, respectively) compared with that of voriconazole (IC90, &gt;3\u2009mg\/L and &gt;10 mg\/L, respectively). In vivo, once-daily intranasal administration of PC1244 (0.56\u201370\u2009\u03bcg\/mouse) to the A. fumigatus (AF91 with M220V)-infected mice reduced pulmonary fungal load and serum galactomannan more than intranasal posaconazole.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PC1244 has the potential to become a novel topical treatment of azole-resistant pulmonary aspergillosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkz302","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T07:07:57Z","timestamp":1561619277000},"page":"2950-2958","source":"Crossref","is-referenced-by-count":15,"title":["Anti-fungal activity of a novel triazole, PC1244, against emerging azole-resistant Aspergillus fumigatus and other species of Aspergillus"],"prefix":"10.1093","volume":"74","author":[{"given":"Thomas","family":"Colley","sequence":"first","affiliation":[{"name":"Pulmocide Ltd, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheshta","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Alanio","sequence":"additional","affiliation":[{"name":"Institut Pasteur, CNRS, Molecular Mycology Unit, French National Reference Center for Invasive Mycoses & Antifungals, URA3012, Paris, France"},{"name":"Paris Diderot, Sorbonne Paris Cit\u00e9 University, Paris, France"},{"name":"Parasitology-Mycology Laboratory, Saint Louis Hospital, Assistance Publique-H\u00f4pitaux de Paris (APHP), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, Funabashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Daly","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Nakaoki","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, Funabashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Nishimoto","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, Funabashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Bretagne","sequence":"additional","affiliation":[{"name":"Institut Pasteur, CNRS, Molecular Mycology Unit, French National Reference Center for Invasive Mycoses & Antifungals, URA3012, Paris, France"},{"name":"Paris Diderot, Sorbonne Paris Cit\u00e9 University, Paris, France"},{"name":"Parasitology-Mycology Laboratory, Saint Louis Hospital, Assistance Publique-H\u00f4pitaux de Paris (APHP), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Kizawa","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, Funabashi, Japan"}],"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":"Kazuhiro","family":"Ito","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3253-6080","authenticated-orcid":false,"given":"Jacques F","family":"Meis","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands"},{"name":"Center of Expertise in Mycology Radboudumc\/Canisius Wilhelmina Hospital, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Chowdhary","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,30]]},"reference":[{"key":"2019092005515198400_dkz302-B1","doi-asserted-by":"crossref","first-page":"e219.","DOI":"10.1371\/journal.pmed.0050219","article-title":"Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism","volume":"5","author":"Snelders","year":"2008","journal-title":"PLoS Med"},{"key":"2019092005515198400_dkz302-B2","doi-asserted-by":"crossref","first-page":"e31801.","DOI":"10.1371\/journal.pone.0031801","article-title":"Triazole fungicides can induce cross-resistance to medical triazoles in Aspergillus fumigatus","volume":"7","author":"Snelders","year":"2012","journal-title":"PLoS One"},{"key":"2019092005515198400_dkz302-B3","doi-asserted-by":"crossref","first-page":"e1003633.","DOI":"10.1371\/journal.ppat.1003633","article-title":"Emergence of azole-resistant Aspergillus fumigatus strains due 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Germany","volume":"59","author":"Bader","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"key":"2019092005515198400_dkz302-B7","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jgar.2015.01.005","article-title":"Triazole-resistant Aspergillus fumigatus harbouring G54 mutation: is it de novo or environmentally acquired?","volume":"3","author":"Sharma","year":"2015","journal-title":"J Glob Antimicrob Resist"},{"key":"2019092005515198400_dkz302-B8","doi-asserted-by":"crossref","first-page":"e01941-17.","DOI":"10.1128\/AAC.01941-17","article-title":"In vitro and in vivo efficacy of a novel and long-acting fungicidal azole, PC1244, on Aspergillus fumigatus infection","volume":"62","author":"Colley","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2019092005515198400_dkz302-B9","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1128\/JCM.03182-13","article-title":"Azole-resistant Aspergillus fumigatus isolate with the TR34\/L98H mutation in both a fungicide-sprayed field and the lung of a hematopoietic stem cell transplant recipient with invasive aspergillosis","volume":"52","author":"Rocchi","year":"2014","journal-title":"J Clin Microbiol"},{"key":"2019092005515198400_dkz302-B10","doi-asserted-by":"crossref","first-page":"e02280-16","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":"2019092005515198400_dkz302-B11","doi-asserted-by":"crossref","first-page":"E103.","DOI":"10.3390\/jof4030103","article-title":"Itraconazole, voriconazole, and posaconazole CLSI MIC distributions for wild-type and azole-resistant Aspergillus fumigatus isolates","volume":"4","author":"Buil","year":"2018","journal-title":"J Fungi (Basel)"},{"key":"2019092005515198400_dkz302-B12","volume-title":"Reference Method for 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