{"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":1791414140373,"version":"4.3.3"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"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":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    DS-2969b is a novel GyrB inhibitor that is currently under clinical development for the treatment of\n                    <jats:named-content content-type=\"genus-species\">Clostridium difficile<\/jats:named-content>\n                    infection (CDI). In this study, the\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    activities of DS-2969b were evaluated. DS-2969b inhibited the supercoiling activity of\n                    <jats:named-content content-type=\"genus-species\">C. difficile<\/jats:named-content>\n                    DNA gyrase. DS-2969b showed potent\n                    <jats:italic>in vitro<\/jats:italic>\n                    activity against\n                    <jats:named-content content-type=\"genus-species\">C. difficile<\/jats:named-content>\n                    clinical isolates with a MIC\n                    <jats:sub>90<\/jats:sub>\n                    of 0.06 \u03bcg\/ml, which was 2-, 32-, and 16-fold lower than the MIC\n                    <jats:sub>90<\/jats:sub>\n                    s of fidaxomicin, vancomycin, and metronidazole, respectively. DS-2969b did not select spontaneously resistant mutants of various\n                    <jats:named-content content-type=\"genus-species\">C. difficile<\/jats:named-content>\n                    strains at 4\u00d7 MIC, and the frequency of resistance development was less than 4.8 \u00d7 10\n                    <jats:sup>\u22129<\/jats:sup>\n                    . In a hamster CDI model, 5-day oral administration of DS-2969b conferred complete protection from recurrence and mortality at 0.3 mg\/kg of body weight once a day, in contrast to a 50% survival rate with fidaxomicin at 3 mg\/kg once a day and 0% with vancomycin at a 50-mg\/kg\/dose twice a day. Even a single oral administration of 1 mg\/kg of DS-2969b in the CDI model exhibited 100% animal survival without recurrence. DS-2969b was also efficacious by 5-day subcutaneous administration in the CDI model. DS-2969b showed similar levels of fecal excretion after intravenous and oral administrations in rats. These data support further development of DS-2969b as a drug for oral and intravenous treatment of CDI.\n                  <\/jats:p>","DOI":"10.1128\/aac.02157-17","type":"journal-article","created":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T09:38:59Z","timestamp":1518082739000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["<i>In Vitro<\/i>\n                    and\n                    <i>In Vivo<\/i>\n                    Activities of DS-2969b, a Novel GyrB Inhibitor, against Clostridium difficile"],"prefix":"10.1128","volume":"62","author":[{"given":"Tarun","family":"Mathur","sequence":"first","affiliation":[{"name":"Department of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarani Kanta","family":"Barman","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diksha","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj Kumar","family":"Khera","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Yamada","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd., Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd., Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilip Jatashankar","family":"Upadhyay","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhisa","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.190"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2164"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00082-09"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2013.7056"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-3049"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/676875"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408913"},{"key":"e_1_3_2_9_2","volume-title":"Antibiotic resistance threats in the United States","author":"Centers for Disease Control and Prevention","year":"2013","unstructured":"Centers for Disease Control and Prevention. 2013. Antibiotic resistance threats in the United States, 2013. Centers for Disease Control and Prevention, Atlanta, GA. https:\/\/www.cdc.gov\/drugresistance\/pdf\/ar-threats-2013-508.pdf."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mimet.2011.07.017"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2008.01992.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1413-8670(12)70320-3"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir643"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00504-15"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0910812"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","unstructured":"Mathur T Singh D Ganghadharan R Kumar M Upadhyay D Masuda N. 2017. In vitro activities of DS-2969b a novel GyrB inhibitor against Clostridium difficile . 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