{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T18:48:38Z","timestamp":1769280518108,"version":"3.49.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>Cefquinome, the fourth-generation cephalosporin applied solely for veterinary medicine, is commonly used for bovine mastitis caused by <jats:italic>Staphylococcus aureus<\/jats:italic>. The present study aims to establish an optimal dose and provide a PK\/PD Cutoff value (CO<jats:sub>PD<\/jats:sub>) for cefquinome against <jats:italic>S. aureus<\/jats:italic> based on <jats:italic>ex vivo<\/jats:italic> pharmacokinetics and pharmacodynamics (PK\/PD) integration. This study investigated the pharmacokinetics (PK) of cefquinome when administered as three consecutive intramammary (IMM) doses of cefquinome in three healthy dairy cows at 75 mg\/gland. Drug concentration was determined by HPLC-MS\/MS assay. The <jats:italic>ex vivo<\/jats:italic> pharmacodynamics (PD) of cefquinome were evaluated by using a milk sample from a PK experiment. The relationship between the AUC\/ MIC of cefquinome and bacterial loading reduction was simulated using a Sigmoid Emax model. The cefquinome concentration in milk attained a maximum level of 1.55 \u00b1 0.21 mg\/mL at 1.8 h after the third administration. The mean value of the area under the concentration-time curve (AUC<jats:sub>0\u221224<\/jats:sub>) was 26.12 \u00b1 2.42 mg\u00b7h\/mL after the third administration. The elimination half-life was 10.6 h. For PD profile, the MICs of cefquinome in milk were 2\u20134 times higher than those in the broth. <jats:italic>In vitro<\/jats:italic> time-killing curve shows that initial bacterial concentration has a huge impact on antibacterial effect on three strains. The antibacterial effect was weakened with the initial bacterial concentration increasing from 10<jats:sup>6<\/jats:sup> to 10<jats:sup>8<\/jats:sup> CFU\/mL. The AUC<jats:sub>0\u221224h<\/jats:sub>\/MIC index correlated well with <jats:italic>ex vivo<\/jats:italic> efficacy both for the initial inoculum of 10<jats:sup>6<\/jats:sup> CFU\/mL and 10<jats:sup>8<\/jats:sup> CFU\/mL (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup> &amp;gt; 0.84). According to the inhibitory sigmoid E<jats:sub>max<\/jats:sub> model analysis, the PK\/PD surrogate (AUC<jats:sub>0\u221224<\/jats:sub>\/MIC) values were 8,638, 1,397, and 3,851 for bactericidal effect (<jats:italic>E<\/jats:italic> = \u22123) with an initial inoculum of 10<jats:sup>6<\/jats:sup> CFU\/mL, while the corresponding values were 12,266, 2,295, and 5,337, respectively, with the initial inoculum of 10<jats:sup>8<\/jats:sup> CFU\/mL. The <jats:italic>ex vivo<\/jats:italic> PK\/PD based population dose prediction indicated a target attainment rate (TAR) of 90% of 55 mg\/gland\/12 h. The CO<jats:sub>PD<\/jats:sub> for cefquinome against <jats:italic>S. aureus<\/jats:italic> was 2 \u03bcg\/mL under the recommended dose of 55 mg\/gland\/12 h. However, it should be validated in clinical practice in future investigations. These results contribute to the rational use of cefquinome for mastitis treatment in clinical veterinary medicine.<\/jats:p>","DOI":"10.3389\/fvets.2022.837882","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T07:36:01Z","timestamp":1646724961000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Ex Vivo Pharmacokinetics and Pharmacodynamics Modeling and Optimal Regimens Evaluation of Cefquinome Against Bovine Mastitis Caused by Staphylococcus aureus"],"prefix":"10.3389","volume":"9","author":[{"given":"Li-jie","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke-xu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-qiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1053\/tvjl.2002.0724","article-title":"Bovine mastitis: an evolving disease","volume":"164","author":"Bradley","year":"2002","journal-title":"Vet J."},{"key":"B2","first-page":"718","article-title":"Efficacy of cefquinome for-the treatment of bovine mastitis - 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