{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:13:52Z","timestamp":1789910032523,"version":"4.0.1"},"reference-count":18,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The increasing global burden of multidrug-resistant tuberculosis (MDR-TB) requires reliable drug susceptibility testing that accurately characterizes susceptibility and resistance of pathogenic bacteria to effectively treat patients with this deadly disease. Delamanid is an anti-TB agent first approved in the European Union in 2014 for the treatment of pulmonary MDR-TB in adults. Using the agar proportion method, delamanid MIC was determined for 460 isolates: 316 from patients enrolled in a phase 2 global clinical trial, 76 from two phase 2 early bactericidal activity trials conducted in South Africa, and 68 isolates obtained outside clinical trials (45 from Japanese patients and 23 from South African patients). With the exception of two isolates, MICs ranged from 0.001 to 0.05 \u03bcg\/ml, resulting in an MIC\n            <jats:sub>50<\/jats:sub>\n            of 0.004 \u03bcg\/ml and an MIC\n            <jats:sub>90<\/jats:sub>\n            of 0.012 \u03bcg\/ml. Various degrees of resistance to other anti-TB drugs did not affect the distribution of MICs, nor did origin of isolates from regions\/countries other than South Africa. A critical concentration\/breakpoint of 0.2 \u03bcg\/ml can be used to define susceptible and resistant isolates based on the distribution of MICs and available pharmacokinetic data. Thus, clinical isolates from delamanid-naive patients with tuberculosis have a very low MIC for delamanid and baseline resistance is rare, demonstrating the potential potency of delamanid and supporting its use in an optimized background treatment regimen for MDR-TB.\n          <\/jats:p>","DOI":"10.1128\/aac.03014-15","type":"journal-article","created":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T02:49:37Z","timestamp":1458010177000},"page":"3316-3322","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":52,"title":["MIC of Delamanid (OPC-67683) against Mycobacterium tuberculosis Clinical Isolates and a Proposed Critical Concentration"],"prefix":"10.1128","volume":"60","author":[{"given":"Kelly","family":"Stinson","sequence":"first","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Inc., Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Kurepina","sequence":"additional","affiliation":[{"name":"Public Health Research Institute Tuberculosis Center, New Jersey Medical School\u2014Rutgers, The State University of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amour","family":"Venter","sequence":"additional","affiliation":[{"name":"MRC Centre for Tuberculosis Research, DST\/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoru","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliano","family":"Timm","sequence":"additional","affiliation":[{"name":"Microbiocon, LLC, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Shashkina","sequence":"additional","affiliation":[{"name":"Public Health Research Institute Tuberculosis Center, New Jersey Medical School\u2014Rutgers, The State University of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry N.","family":"Kreiswirth","sequence":"additional","affiliation":[{"name":"Public Health Research Institute Tuberculosis Center, New Jersey Medical School\u2014Rutgers, The State University of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongge","family":"Liu","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Inc., Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Geiter","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Inc., Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Document WHO\/HTM\/TB\/2015.22","author":"World Health Organization","year":"2015","unstructured":"World Health Organization. 2015. Global tuberculosis report. Document WHO\/HTM\/TB\/2015.22. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030466"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.10.0616"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112433"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00125812"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00176314"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1415332"},{"key":"e_1_3_3_9_2","volume-title":"Document M23-A3","author":"Clinical and Laboratory Standards Institute","year":"2008","unstructured":"Clinical and Laboratory Standards Institute. 2008. Development of in vitro susceptibility testing criteria and quality control parameters; approved guideline, 3rd ed. Document M23-A3. CLSI, Wayne, PA.","edition":"3"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.40.7.2339-2345.2002"},{"key":"e_1_3_3_11_2","first-page":"818","article-title":"Differentiation of Mycobacterium tuberculosis complex by PCR amplification of genomic regions of difference","volume":"10","author":"Warren RM","year":"2006","unstructured":"Warren RM, Gey van Pittius NC, Barnard M, Hesseling A, Engelke E, de Kock M, Gutierrez MC, Chege GK, Victor TC, Hoal EG, van Helden PD. 2006. Differentiation of Mycobacterium tuberculosis complex by PCR amplification of genomic regions of difference. Int J Tuberc Lung Dis 10:818\u2013822.","journal-title":"Int J Tuberc Lung Dis"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2015.07.058"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2006.01454.x"},{"key":"e_1_3_3_14_2","volume-title":"Guidance for industry: microbiological data for systemic antibacterial drug products: development, analysis, and presentation","author":"US Department of Health and Human Services\/Food and Drug Administration Center for Drug Evaluation and Research","year":"2009","unstructured":"US Department of Health and Human Services\/Food and Drug Administration Center for Drug Evaluation and Research. 2009. Guidance for industry: microbiological data for systemic antibacterial drug products: development, analysis, and presentation. HHS\/FDA, Rockville, MD."},{"key":"e_1_3_3_15_2","volume-title":"Assessment report: Deltyba","author":"European Medicines Agency","year":"2013","unstructured":"European Medicines Agency. 2013. Assessment report: Deltyba. European Medicines Agency, London, England."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00308-15"},{"key":"e_1_3_3_17_2","volume-title":"Int Chemother Antimicrob Agents Chemother (ICAAC)","author":"Doi N","year":"2006","unstructured":"Doi N, Disratthakit A. 2006. Characteristic anti-mycobacterial spectra of the novel anti-TB drug candidates OPC-67683 and PA-824, poster F1-1377a. Int Chemother Antimicrob Agents Chemother (ICAAC). American Society for Microbiology, Washington, DC."},{"key":"e_1_3_3_18_2","volume-title":"Document WHO\/HTM\/TB\/2014.11","author":"World Health Organization","year":"2014","unstructured":"World Health Organization. 2014. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. Document WHO\/HTM\/TB\/2014.11. World Health Organization, Geneva, Switzerland. http:\/\/apps.who.int\/iris\/bitstream\/10665\/130918\/1\/9789241548809_eng.pdf."},{"key":"e_1_3_3_19_2","volume-title":"Document WHO\/HTM\/TB2014.23","author":"World Health Organization","year":"2014","unstructured":"World Health Organization. 2014. The use of delamanid in the treatment of multidrug-resistant tuberculosis: interim policy guidance. Document WHO\/HTM\/TB2014.23. World Health Organization, Geneva, Switzerland."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.03014-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.03014-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:50:27Z","timestamp":1645476627000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.03014-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6]]},"references-count":18,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1128\/AAC.03014-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.03014-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6]]},"assertion":[{"value":"2015-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-05-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}