{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T09:29:39Z","timestamp":1740130179522,"version":"3.37.3"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical Co., Ltd.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP21wm0125008"],"award-info":[{"award-number":["JP21wm0125008"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Enteric infections are a major public health issue in developing countries. Antimicrobial resistance is also a problem for enteric infection. OPS-2071 is a novel quinolone antibiotic with low oral absorption and potent antibacterial activity against Clostridioides difficile.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>This study was conducted to confirm the antimicrobial activity of OPS-2071 against major enteropathogenic bacteria and to evaluate the risk of emergence of drug resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The antibacterial activity was evaluated by the agar dilution method. The inhibitory activity against DNA gyrase and topoisomerase IV was determined by supercoiling assay and decatenation assay, respectively. The mutant prevention concentration and frequency of spontaneous resistance were determined by inoculation on drug-containing agar.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Compared with the reference drugs, the antibacterial activity of OPS-2071 was more potent against Gram-positive bacteria and Campylobacter jejuni, including quinolone-resistant strains. Against other Gram-negative bacteria, OPS-2071 was comparable to existing quinolones. The inhibitory activities against DNA gyrase with quinolone-resistant mutations closely correlated with the antibacterial activity. Spontaneous resistance to OPS-2071 was not observed in Staphylococcus aureus and Escherichia coli and was lower than that of existing quinolones and higher than that of azithromycin in C. jejuni. The mutant prevention concentration of OPS-2071 was lower than that of tested compounds in S. aureus and C. jejuni and slightly higher than that of existing quinolones in E. coli.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The broad and potent in vitro antibacterial activity and lower risk of drug resistance suggested that OPS-2071 may be useful for enteric infections caused by major pathogens including quinolone-resistant Campylobacter.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac308","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T05:34:01Z","timestamp":1663133641000},"page":"3248-3255","source":"Crossref","is-referenced-by-count":3,"title":["<i>In vitro<\/i> antibacterial activity of OPS-2071 against Gram-positive and Gram-negative enteropathogenic bacteria"],"prefix":"10.1093","volume":"77","author":[{"given":"Daisuke","family":"Oka","sequence":"first","affiliation":[{"name":"Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd. , Tokushima , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruchirada","family":"Changkwanyeun","sequence":"additional","affiliation":[{"name":"Division of Bioresources, International Institute for Zoonosis Control, Hokkaido University , Sapporo , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Division of Bioresources, International Institute for Zoonosis Control, Hokkaido University , Sapporo , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chie","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Division of Bioresources, International Institute for Zoonosis Control, Hokkaido University , Sapporo , Japan"},{"name":"International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University , Sapporo , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-1494","authenticated-orcid":false,"given":"Yasuhiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Bioresources, International Institute for Zoonosis Control, Hokkaido University , Sapporo , Japan"},{"name":"International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University , Sapporo , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Pharmaceutical Business Division, Otsuka Pharmaceutical Co., Ltd. , Tokyo , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"2022112816500181500_dkac308-B1","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1172\/JCI34005","article-title":"Enteric infections, diarrhea, and their impact on function and development","volume":"118","author":"Petri","year":"2008","journal-title":"J Clin Invest"},{"key":"2022112816500181500_dkac308-B2","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/S0140-6736(18)32203-7","article-title":"Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"GBD 2017 Causes of Death Collaborators","year":"2018","journal-title":"Lancet"},{"key":"2022112816500181500_dkac308-B3","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0140-6736(13)60844-2","article-title":"Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study. 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