{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:49:06Z","timestamp":1760233746674,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Venatorx","award":["HHSN272201600029C"],"award-info":[{"award-number":["HHSN272201600029C"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Efforts to develop and pair novel oral \u03b2-lactamase inhibitors with existing \u03b2-lactam agents to treat extended spectrum \u03b2-lactamase (ESBL) and carbapenemase-producing Enterobacterales are gaining ground. Ceftibuten is an oral third-generation cephalosporin capable of achieving high urine concentrations; however, there are no robust data describing its pharmacodynamic profile. This study characterizes ceftibuten pharmacokinetics and pharmacodynamics in a neutropenic murine thigh infection model. Enterobacterales isolates expressing no known clinically-relevant enzymatic resistance (n = 7) or harboring an ESBL (n = 2) were evaluated. The ceftibuten minimum inhibitory concentrations (MICs) were 0.03\u20134 mg\/L. Nine ceftibuten regimens, including a human-simulated regimen (HSR) equivalent to clinical ceftibuten doses of 300\u2009mg taken orally every 8 h, were utilized to achieve various fT &gt; MICs. A sigmoidal Emax model was fitted to fT &gt; MIC vs. change in log10 CFU\/thigh to determine the requirements for net stasis and 1-log10 CFU\/thigh bacterial burden reduction. The growth of the 0 h and 24 h control groups was 5.97 \u00b1 0.37 and 8.51 \u00b1 0.84 log10 CFU\/thigh, respectively. Ceftibuten HSR resulted in a -0.49 to -1.43 log10 CFU\/thigh bacterial burden reduction at 24 h across the isolates. Stasis and 1-log10 CFU\/thigh reduction were achieved with a fT &gt; MIC of 39% and 67%, respectively. The fT &gt; MIC targets identified can be used to guide ceftibuten dosage selection to optimize the likelihood of clinical efficacy.<\/jats:p>","DOI":"10.3390\/antibiotics10020201","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T09:06:10Z","timestamp":1613725570000},"page":"201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacodynamics of Ceftibuten: An Assessment of an Oral Cephalosporin against Enterobacterales in a Neutropenic Murine Thigh Model"],"prefix":"10.3390","volume":"10","author":[{"given":"Maxwell J.","family":"Lasko","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-0924","authenticated-orcid":false,"given":"Tomefa E.","family":"Asempa","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA"},{"name":"Division of Infectious Diseases, Hartford Hospital, Hartford, CT 06102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"doi-asserted-by":"crossref","unstructured":"Bush, K., and Bradford, P.A. (2020). Epidemiology of \u03b2-Lactamase-Producing Pathogens. Clin. Microbiol. Rev., 33.","key":"ref_1","DOI":"10.1128\/CMR.00047-19"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1001\/jama.2015.12480","article-title":"Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012\u20132013","volume":"314","author":"Guh","year":"2015","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1017\/ice.2017.156","article-title":"Incidence of Extended-Spectrum \u03b2-Lactamase (ESBL)-Producing Escherichia coli and Klebsiella Infections in the United States: A Systematic Literature Review","volume":"38","author":"McDanel","year":"2017","journal-title":"Infect. Control Hosp. 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