{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:02:20Z","timestamp":1791414140430,"version":"4.3.3"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Tuberculosis (TB) treatment is long and requires multiple drugs, likely due to various phenotypes of TB bacilli with variable drug susceptibilities. Drugs with broad activity are urgently needed. This study aimed to evaluate delamanid's activity against growing or dormant bacilli\n            <jats:italic>in vitro<\/jats:italic>\n            as well as\n            <jats:italic>in vivo<\/jats:italic>\n            . Cultures of\n            <jats:named-content content-type=\"genus-species\">Mycobacterium bovis<\/jats:named-content>\n            BCG Tokyo under aerobic and anaerobic conditions were used to study the activity of delamanid against growing and dormant bacilli, respectively. Delamanid exhibited significant bactericidal activity against replicating and dormant bacilli at or above concentrations of 0.016 and 0.4 mg\/liter, respectively. To evaluate delamanid's antituberculosis activity\n            <jats:italic>in vivo<\/jats:italic>\n            , we used a guinea pig model of chronic TB infection in which the lung lesions were similar to those in human TB disease. In the guinea pig TB model, a daily dose of 100 mg delamanid\/kg of body weight for 4 or 8 weeks demonstrated strong bactericidal activity against\n            <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n            . Importantly, histological examination revealed that delamanid killed TB bacilli within hypoxic lesions of the lung. The combination regimens containing delamanid with rifampin and pyrazinamide or delamanid with levofloxacin, ethionamide, pyrazinamide, and amikacin were more effective than the standard regimen (rifampin, isoniazid, and pyrazinamide). Our data show that delamanid is effective in killing both growing and dormant bacilli\n            <jats:italic>in vitro<\/jats:italic>\n            and in the guinea pig TB model. Adding delamanid to current TB regimens may improve treatment outcomes, as demonstrated in recent clinical trials with pulmonary multidrug-resistant (MDR) TB patients. Delamanid may be an important drug for consideration in the construction of new regimens to shorten TB treatment duration.\n          <\/jats:p>","DOI":"10.1128\/aac.02402-16","type":"journal-article","created":{"date-parts":[[2017,4,4]],"date-time":"2017-04-04T00:37:41Z","timestamp":1491266261000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Delamanid Kills Dormant Mycobacteria\n            <i>In Vitro<\/i>\n            and in a Guinea Pig Model of Tuberculosis"],"prefix":"10.1128","volume":"61","author":[{"given":"Xiuhao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Hashizume","sequence":"additional","affiliation":[{"name":"Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Tomishige","sequence":"additional","affiliation":[{"name":"Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izuru","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Matsuba","sequence":"additional","affiliation":[{"name":"Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoru","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuki","family":"Kitamoto","sequence":"additional","affiliation":[{"name":"Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erina","family":"Hanaki","sequence":"additional","affiliation":[{"name":"Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Ohba","sequence":"additional","affiliation":[{"name":"Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Global tuberculosis report 2016","author":"World Health Organization","year":"2016","unstructured":"World Health Organization. 2016. Global tuberculosis report 2016. Document WHO\/HTM\/TB\/2016.13. World Health Organization, Geneva, Switzerland. http:\/\/www.who.int\/tb\/publications\/global_report\/en\/."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1816"},{"key":"e_1_3_3_4_2","volume-title":"Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis","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."},{"key":"e_1_3_3_5_2","volume-title":"WHO treatment guidelines for drug-resistant tuberculosis, 2016 update","author":"World Health Organization","year":"2016","unstructured":"World Health Organization. 2016. WHO treatment guidelines for drug-resistant tuberculosis, 2016 update. Document WHO\/HTM\/TB\/2016.04. 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