{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:35:40Z","timestamp":1792002940738,"version":"4.4.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"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":[[2023,9,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            This study compared the efficacy of flomoxef with other \u03b2-lactam antibiotics against extended-spectrum \u03b2-lactamases (ESBL)-producing bacteria of clinical relevance. First, the prevalence and \u03b2-lactamase genotypes of ESBL-producing strains among\n            <jats:italic>Escherichia coli<\/jats:italic>\n            and\n            <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n            isolates collected in Japan from 2004 to 2018 were investigated. High MIC\n            <jats:sub>90<\/jats:sub>\n            values (&gt;64 \u00b5g\/mL) of ceftriaxone, cefepime, and ceftazidime and low MIC\n            <jats:sub>90<\/jats:sub>\n            values (\u22640.06\u20132 \u00b5g\/mL) of flomoxef, cefmetazole, and meropenem against both species were observed. Second, a chemostat model was used to analyze the efficacy of humanized regimens of three oxacephem\/cephamycin antibiotics (flomoxef, cefmetazole, cefoxitin) and two other antibiotics (meropenem and piperacillin\/tazobactam) in suppressing the growth of five ESBL-producing\n            <jats:italic>E. coli<\/jats:italic>\n            and two\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            strains. Flomoxef, piperacillin\/tazobactam, and meropenem showed good bactericidal effects with &gt;4 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/mL reduction without bacterial regrowth at 24 h even when the MIC of test isolates was &gt;MIC\n            <jats:sub>90<\/jats:sub>\n            . Cefmetazole and cefoxitin resulted in regrowth of test isolates with MIC \u2265MIC\n            <jats:sub>90<\/jats:sub>\n            at 24 h. Cefmetazole, cefoxitin, flomoxef, and meropenem showed increased MICs for regrown samples. A clear relationship between the proportion of time that the free drug concentration exceeded the MIC (%\n            <jats:italic>f<\/jats:italic>\n            T\n            <jats:sub>&gt;MIC<\/jats:sub>\n            ) and antibiotic efficacy was found for flomoxef, cefoxitin, and cefmetazole, and flomoxef had the highest %\n            <jats:italic>f<\/jats:italic>\n            T\n            <jats:sub>&gt;MIC<\/jats:sub>\n            , whereas discrepancies between Clinical and Laboratory Standards Institute breakpoint and bactericidal activity were observed for cefmetazole. Flomoxef was effective in preventing the growth of all ESBL-producing strains, even those with an MIC eight times the MIC\n            <jats:sub>90<\/jats:sub>\n            . Thus, flomoxef may be a good alternative to meropenem in context of carbapenems sparing stewardship.\n          <\/jats:p>","DOI":"10.1128\/aac.00258-23","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T13:02:18Z","timestamp":1692795738000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["<i>In vitro<\/i>\n            efficacy of humanized regimen of flomoxef against extended-spectrum \u03b2-lactamase-producing\n            <i>Escherichia coli<\/i>\n            and\n            <i>Klebsiella pneumoniae<\/i>"],"prefix":"10.1128","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3148-2896","authenticated-orcid":true,"given":"Hidenori","family":"Yamashiro","sequence":"first","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi &amp; Co., Ltd. , Toyonaka, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Kasamatsu","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine , Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Anan","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi &amp; Co., Ltd. , Toyonaka, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Takemura","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi &amp; Co., Ltd. , Toyonaka, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Yamano","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi &amp; Co., Ltd. , Toyonaka, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jtm\/taw102"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-021823"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.2165\/11533040-000000000-00000"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab696"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlab092"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac268"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000598"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.5.858"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.38.466"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab468"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.11.012"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2015.01.001"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00701-15"},{"key":"e_1_3_4_15_2","volume-title":"CLSI supplement M100. 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