{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T13:32:42Z","timestamp":1782135162438,"version":"3.54.5"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Research Program of Chongqing Municipal Education Commission","award":["KJZD-K202303501, KJQN-202203511, KJQN-202203504, KJQN-202303507, KJQN-202403510"],"award-info":[{"award-number":["KJZD-K202303501, KJQN-202203511, KJQN-202203504, KJQN-202303507, KJQN-202403510"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>In this study, gamithromycin, a long-acting azalide antibiotic recently introduced for bovine respiratory disease (BRD) treatment, was evaluated for its effectiveness against <jats:italic>Pasteurella multocida<\/jats:italic> using a cattle tissue cage model. Gamithromycin (6\u2009mg\/kg) was administered via both intravenous and subcutaneous routes and the gamithromycin contents in sera, transudates, and exudates were measured using HPLC\/MS-MS. Non-compartmental methods were utilized for assessing pharmacokinetic parameters and an inhibitory sigmoid E<jats:sub>max<\/jats:sub> model determined associations between the pharmacokinetic\/pharmacodynamic (PK\/PD) indices and antibacterial activity. The area under the 24-h concentration-time curve\/minimum inhibitory concentration (AUC<jats:sub>0-24h<\/jats:sub>\/MIC) was found to be an optimal measure of antibacterial activity. The AUC<jats:sub>0-24h<\/jats:sub>\/MIC values over 24\u2009h in sera, transudates, and exudates were 0.27, 0.17, and 0.14, respectively, for bacteriostatic effects, while for bactericidal activity, the AUC<jats:sub>0-24h<\/jats:sub>\/MIC values over 24\u2009h in sera and exudates 3.76 and 5.31, respectively, and for bacterial eradication, the serum value was 18.46. These findings contribute valuable insights into the optimization of gamithromycin dosing regimens for treating respiratory conditions caused by <jats:italic>Pasteurella multocida<\/jats:italic> in cattle.<\/jats:p>","DOI":"10.1371\/journal.pone.0323727","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T17:58:31Z","timestamp":1748541511000},"page":"e0323727","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics\/pharmacodynamics of gamithromycin for treating Pasteurella multocida infection in cattle using a tissue cage model"],"prefix":"10.1371","volume":"20","author":[{"given":"Qingwen","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9103-988X","authenticated-orcid":true,"given":"Xuesong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhi","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"issue":"1","key":"pone.0323727.ref001","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3390\/ani13010075","article-title":"Molecular Epidemiology of Pasteurella multocida Associated with Bovine Respiratory Disease Outbreaks","volume":"13","author":"JM Calder\u00f3n Bernal","year":"2022","journal-title":"Animals (Basel)"},{"key":"pone.0323727.ref002","doi-asserted-by":"crossref","first-page":"108748","DOI":"10.1016\/j.vetmic.2020.108748","article-title":"Bovine Respiratory Syncytial Virus Decreased Pasteurella multocida Adherence by Downregulating the Expression of Intercellular Adhesion Molecule-1 on the Surface of Upper Respiratory Epithelial Cells","volume":"246","author":"PE Sudaryatma","year":"2020","journal-title":"Vet Microbiol"},{"issue":"2","key":"pone.0323727.ref003","doi-asserted-by":"crossref","DOI":"10.1093\/jas\/skaa005","article-title":"An evaluation of the economic effects of bovine respiratory disease on animal performance, carcass traits, and economic outcomes in feedlot cattle defined using four BRD diagnosis methods","volume":"98","author":"C Blakebrough-Hall","year":"2020","journal-title":"J Anim Sci"},{"key":"pone.0323727.ref004","doi-asserted-by":"crossref","first-page":"109779","DOI":"10.1016\/j.vetmic.2023.109779","article-title":"Antimicrobial susceptibility and molecular characteristics of Mycoplasma bovis isolated from cases of bovine respiratory disease in Australian feedlot cattle","volume":"283","author":"MF Hasoon","year":"2023","journal-title":"Vet Microbiol"},{"issue":"1","key":"pone.0323727.ref005","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s12917-024-03988-y","article-title":"Pharmacokinetic\/pharmacodynamic evaluation of gamithromycin against rabbit pasteurellosis","volume":"20","author":"X-Y Wei","year":"2024","journal-title":"BMC Vet Res"},{"issue":"12","key":"pone.0323727.ref006","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s11274-022-03407-0","article-title":"Susceptibility of caprine mastitis pathogens to tildipirosin, gamithromycin, oxytetracycline, and danofloxacin: effect of serum on the in vitro potency of current macrolides","volume":"38","author":"JS Galecio","year":"2022","journal-title":"World J Microbiol Biotechnol"},{"issue":"6","key":"pone.0323727.ref007","doi-asserted-by":"crossref","first-page":"847","DOI":"10.2460\/ajvr.74.6.847","article-title":"Field study of the comparative efficacy of gamithromycin and tulathromycin for the treatment of undifferentiated bovine respiratory disease complex in beef feedlot calves","volume":"74","author":"S Torres","year":"2013","journal-title":"Am J Vet Res"},{"issue":"6","key":"pone.0323727.ref008","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/j.1365-2885.2004.00613.x","article-title":"Integration and modelling of pharmacokinetic and pharmacodynamic data to optimize dosage regimens in veterinary medicine","volume":"27","author":"PL Toutain","year":"2004","journal-title":"J Vet Pharmacol Ther"},{"issue":"1","key":"pone.0323727.ref009","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/jvp.12333","article-title":"Standard PK\/PD concepts can be applied to determine a dosage regimen for a macrolide: the case of tulathromycin in the calf","volume":"40","author":"P-L Toutain","year":"2017","journal-title":"J Vet Pharmacol Ther"},{"issue":"5","key":"pone.0323727.ref010","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.jiac.2015.02.001","article-title":"Applications of the pharmacokinetic\/pharmacodynamic (PK\/PD) analysis of antimicrobial agents","volume":"21","author":"E As\u00edn-Prieto","year":"2015","journal-title":"J Infect Chemother"},{"issue":"6","key":"pone.0323727.ref011","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/jac\/dkm360","article-title":"AUC\/MIC: a PK\/PD index for antibiotics with a time dimension or simply a dimensionless scoring factor?","volume":"60","author":"P-L Toutain","year":"2007","journal-title":"J Antimicrob Chemother"},{"issue":"5","key":"pone.0323727.ref012","doi-asserted-by":"crossref","first-page":"103571","DOI":"10.1016\/j.psj.2024.103571","article-title":"Comparison of gamithromycin residue depletion in yellow-feather and white-feather broilers after one single subcutaneous injection","volume":"103","author":"X-P Li","year":"2024","journal-title":"Poult Sci"},{"key":"pone.0323727.ref013","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.rvsc.2021.11.016","article-title":"Gamithromycin in sheep: Pharmacokinetics and clinical evaluation against ovine footrot","volume":"142","author":"D Hamel","year":"2021","journal-title":"Res Vet Sci"},{"issue":"9","key":"pone.0323727.ref014","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.3382\/ps\/pev217","article-title":"Pharmacokinetic and pharmacodynamic properties of gamithromycin in turkey poults with respect to Ornithobacterium rhinotracheale","volume":"94","author":"A Watteyn","year":"2015","journal-title":"Poult Sci"},{"issue":"1","key":"pone.0323727.ref015","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.rvsc.2013.11.012","article-title":"Pharmacokinetics of gamithromycin after intravenous and subcutaneous administration in pigs","volume":"96","author":"H Wyns","year":"2014","journal-title":"Res Vet Sci"},{"issue":"3","key":"pone.0323727.ref016","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1046\/j.1365-2885.2002.00399.x","article-title":"Pharmacokinetics and pharmacokinetic\/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate","volume":"25","author":"FS Aliabadi","year":"2002","journal-title":"J Vet Pharmacol Ther"},{"key":"pone.0323727.ref017","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3389\/fphar.2017.00392","article-title":"Pharmacokinetic\/Pharmacodynamic Modeling of Tulathromycin against Pasteurella multocida in a Porcine Tissue Cage Model","volume":"8","author":"Q Zhou","year":"2017","journal-title":"Front Pharmacol"},{"key":"pone.0323727.ref018","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.chroma.2015.04.022","article-title":"Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantitative determination of gamithromycin in animal plasma, lung tissue and pulmonary epithelial lining fluid","volume":"1398","author":"S De Baere","year":"2015","journal-title":"J Chromatogr A"},{"key":"pone.0323727.ref019","volume-title":"Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals; approved standard","author":"CLSI","year":"2013"},{"issue":"3","key":"pone.0323727.ref020","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/jvp.12078","article-title":"Pharmacokinetic\/pharmacodynamic relationship of marbofloxacin against Pasteurella multocida in a tissue-cage model in yellow cattle","volume":"37","author":"Q Shan","year":"2014","journal-title":"J Vet Pharmacol Ther"},{"issue":"2","key":"pone.0323727.ref021","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1017\/S146625231500016X","article-title":"A literature review of antimicrobial resistance in Pathogens associated with bovine respiratory disease","volume":"16","author":"KD DeDonder","year":"2015","journal-title":"Anim Health Res Rev"},{"key":"pone.0323727.ref022","doi-asserted-by":"crossref","first-page":"735","DOI":"10.2147\/IDR.S345574","article-title":"Clinical Perspective of Antimicrobial Resistance in Bacteria","volume":"15","author":"Y Zhu","year":"2022","journal-title":"Infect Drug Resist"},{"issue":"6","key":"pone.0323727.ref023","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.3382\/ps.2012-02932","article-title":"Pharmacokinetics of gamithromycin after intravenous and subcutaneous administration in broiler chickens","volume":"92","author":"A Watteyn","year":"2013","journal-title":"Poult Sci"},{"issue":"1","key":"pone.0323727.ref024","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s12917-020-02300-y","article-title":"Epidemiological and PK\/PD cutoff values determination and PK\/PD-based dose assessment of gamithromycin against Haemophilus parasuis in piglets","volume":"16","author":"Y-F Zhou","year":"2020","journal-title":"BMC Vet Res"},{"issue":"3","key":"pone.0323727.ref025","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.1365-2885.2009.01125.x","article-title":"Pharmacokinetics of gamithromycin in cattle with comparison of plasma and lung tissue concentrations and plasma antibacterial activity","volume":"33","author":"RA Huang","year":"2010","journal-title":"J Vet Pharmacol Ther"},{"issue":"1","key":"pone.0323727.ref026","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1128\/AAC.00133-06","article-title":"Interpretation of antibiotic concentration ratios measured in epithelial lining fluid","volume":"52","author":"S Kiem","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"issue":"5","key":"pone.0323727.ref027","article-title":"In Vivo Pharmacokinetic and Pharmacodynamic Profiles of Antofloxacin against Klebsiella pneumoniae in a Neutropenic Murine Lung Infection Model","volume":"61","author":"Y-F Zhou","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pone.0323727.ref028","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s12917-021-02908-8","article-title":"Pharmacokinetics and pharmacodynamics of enrofloxacin treatment of Escherichia coli in a murine thigh infection modeling","volume":"17","author":"X Liu","year":"2021","journal-title":"BMC Vet Res"},{"key":"pone.0323727.ref029","doi-asserted-by":"crossref","first-page":"5465678","DOI":"10.1155\/2016\/5465678","article-title":"Application of PK\/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction","volume":"2016","author":"I Ahmad","year":"2016","journal-title":"Biomed Res Int"},{"key":"pone.0323727.ref030","doi-asserted-by":"crossref","first-page":"860472","DOI":"10.3389\/fvets.2022.860472","article-title":"Pharmacodynamic Parameters of Pharmacokinetic\/Pharmacodynamic (PK\/PD) Integration Models","volume":"9","author":"L Zhang","year":"2022","journal-title":"Front Vet Sci"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0323727","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T17:58:43Z","timestamp":1748541523000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0323727"}},"subtitle":[],"editor":[{"given":"Arifa","family":"Mehreen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,5,29]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0323727","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,29]]}}}