{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:02:21Z","timestamp":1791414141721,"version":"4.3.3"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"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":[[2018,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    DS-2969b is a novel GyrB inhibitor under clinical development. In this study, the\n                    <jats:italic>in vitro<\/jats:italic>\n                    activity of DS-2969b and the\n                    <jats:italic>in vivo<\/jats:italic>\n                    activities of DS-2969b and its water-soluble prodrug, DS11960558, against methicillin-resistant\n                    <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n                    (MRSA) were evaluated. DS-2969b inhibited the supercoiling activity of\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    DNA gyrase and the decatenation activity of its topoisomerase IV. DS-2969b showed antibacterial activity against Gram-positive aerobes but not against Gram-negative aerobes, except for\n                    <jats:named-content content-type=\"genus-species\">Moraxella catarrhalis<\/jats:named-content>\n                    and\n                    <jats:named-content content-type=\"genus-species\">Haemophilus influenzae<\/jats:named-content>\n                    . DS-2969b was active against MRSA with an MIC\n                    <jats:sub>90<\/jats:sub>\n                    of 0.25 \u03bcg\/ml, which was 8-fold lower than that of linezolid. The presence of a pulmonary surfactant did not affect the MIC of DS-2969b. DS-2969b showed time-dependent slow killing against MRSA. The frequency of spontaneous resistance development was less than 6.2 \u00d7 10\n                    <jats:sup>\u221210<\/jats:sup>\n                    in all four\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    isolates at 4\u00d7 MIC of DS-2969b. In a neutropenic MRSA-induced murine muscle infection model, DS-2969b was more efficacious than linezolid by both the subcutaneous and oral routes. DS-2969b and DS11960558 showed efficacy in a neutropenic murine MRSA lung infection model. The pharmacokinetics and pharmacodynamics of DS-2969b and DS11960558 against MRSA were characterized in a neutropenic murine thigh infection model; the percentage of time during the dosing period in which the free drug concentration exceeded the MIC (\n                    <jats:italic>fT<\/jats:italic>\n                    <jats:sub>MIC<\/jats:sub>\n                    ) correlated best with\n                    <jats:italic>in vivo<\/jats:italic>\n                    efficacy, and the static percent\n                    <jats:italic>fT<\/jats:italic>\n                    <jats:sub>MIC<\/jats:sub>\n                    was 43 to 49%. A sufficient\n                    <jats:italic>fT<\/jats:italic>\n                    <jats:sub>MIC<\/jats:sub>\n                    was observed in a phase 1 multiple-ascending-dose study of DS-2969b given orally at 400 mg once a day. These results suggest that DS11960558 and DS-2969b have potential for use as intravenous-to-oral step-down therapy for treating MRSA infections with a higher efficacy than linezolid.\n                  <\/jats:p>","DOI":"10.1128\/aac.02556-17","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T06:12:01Z","timestamp":1522649521000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["<i>In Vitro<\/i>\n                    and\n                    <i>In Vivo<\/i>\n                    Activities of DS-2969b, a Novel GyrB Inhibitor, and Its Water-Soluble Prodrug, DS11960558, against Methicillin-Resistant Staphylococcus aureus"],"prefix":"10.1128","volume":"62","author":[{"given":"Tarani Kanta","family":"Barman","sequence":"first","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":"Tarun","family":"Mathur","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiko","family":"Namba","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd., Tokyo, Japan"}],"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":"Tridib","family":"Chaira","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Metabolism, Daiichi Sankyo India Pharma Private Limited, Gurgaon, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Kurosaka","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd., Tokyo, Japan"}],"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":"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"},{"name":"Daiichi Sankyo Co., Ltd., Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(59)90383-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2012.27"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir153"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/2047-2994-3-18"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg457"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2006.03.012"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2016.11.016"},{"key":"e_1_3_2_9_2","volume-title":"Antimicrobial resistance: tackling a crisis for the health and wealth of nations","author":"O'Neill J","year":"2014","unstructured":"O'Neill J. 2014. 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