{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T22:13:06Z","timestamp":1757542386697,"version":"3.41.2"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The spread of extended-spectrum \u03b2-lactamase-producing Enterobacteriaceae (ESBL-E) is a serious concern in companion animal medicine owing to their ability to develop multidrug resistance. Cefmetazole (CMZ) is a candidate drug for treating ESBL-E infections; however, its regimen in dogs has not been established. In this study, we investigated the pharmacokinetic (PK) indices of CMZ in dogs and performed PK\u2013pharmacodynamic (PD) analyses using Monte Carlo Simulation (MCS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In total, six healthy dogs received an intravenous bolus dose of CMZ (40\u2009mg\/kg body weight). Serum CMZ concentrations were evaluated using liquid chromatography\u2013mass spectrometry, and PK indices were determined based on non-compartmental analysis. The PK\u2013PD cut-off (COPD) values were calculated as the highest minimum inhibitory concentration (MIC) that achieved \u226590% probability of target attainment for a target value of unbounded drug concentration exceeding 40% of the dosing interval. The cumulative fraction of response (CFR) was calculated based on the MIC distribution of wild-type ESBL-E from companion animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The area under the concentration\u2013time curve and elimination half-time were 103.36\u2009\u00b1\u20097.49\u2009mg\u00b7h\/L and 0.84\u2009\u00b1\u20090.07\u2009h, respectively. MCS analysis revealed that COPD values for regimens of 40\u2009mg\/kg q12, q8h, and q6h were\u2009\u2264\u20090.5, \u22642, and\u2009\u2264\u20094\u2009\u03bcg\/mL, respectively. A regimen of 40\u2009mg\/kg q6h was estimated to achieve a CFR of 80\u201390% for <jats:italic>Escherichia coli<\/jats:italic> and <jats:italic>Klebsiella pneumoniae<\/jats:italic>. By contrast, all regimens exhibited a CFR of \u226470% for <jats:italic>Proteus mirabilis<\/jats:italic> and <jats:italic>Enterobacter cloacae.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We conclude that CMZ at 40\u2009mg\/kg q6h could be a viable treatment regimen for dogs infected with ESBL-producing <jats:italic>Escherichia coli<\/jats:italic> and <jats:italic>Klebsiella pneumoniae<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fvets.2023.1270137","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T04:26:51Z","timestamp":1695961611000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacokinetic\u2013pharmacodynamic analysis of cefmetazole against extended-spectrum \u03b2-lactamase-producing Enterobacteriaceae in dogs using Monte Carlo Simulation"],"prefix":"10.3389","volume":"10","author":[{"given":"Mizuki","family":"Kusumoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoki","family":"Motegi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruna","family":"Uno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mizuki","family":"Yokono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuki","family":"Harada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S1473-3099(08)70041-0","article-title":"Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health 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