Yang Qingwen, Liu Xuesong, Lv Yongzhi, Li Yushen
Laboratory of Veterinary Pharmacology, Department of Animal Science and Technology, Chongqing Three Gorges Vocational College, Chongqing, China.
Heilongjiang Province Key Laboratory of Veterinary Drugs, Branch of Animal Husbandry and Veterinary of Heilongjiang Academy of Agricultural Sciences, Qiqihar, China.
PLoS One. 2025 May 29;20(5):e0323727. doi: 10.1371/journal.pone.0323727. eCollection 2025.
In this study, gamithromycin, a long-acting azalide antibiotic recently introduced for bovine respiratory disease (BRD) treatment, was evaluated for its effectiveness against Pasteurella multocida using a cattle tissue cage model. Gamithromycin (6 mg/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 Emax 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 (AUC0-24h/MIC) was found to be an optimal measure of antibacterial activity. The AUC0-24h/MIC values over 24 h in sera, transudates, and exudates were 0.27, 0.17, and 0.14, respectively, for bacteriostatic effects, while for bactericidal activity, the AUC0-24h/MIC values over 24 h 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 Pasteurella multocida in cattle.
在本研究中，使用牛组织笼模型评估了加米霉素（一种最近用于治疗牛呼吸道疾病（BRD）的长效氮杂内酯类抗生素）对多杀性巴氏杆菌的有效性。通过静脉内和皮下途径给予加米霉素（6mg/kg），并使用HPLC/MS-MS测定血清、漏出液和渗出液中的加米霉素含量。采用非房室方法评估药代动力学参数，并使用抑制性S形Emax模型确定药代动力学/药效学（PK/PD）指标与抗菌活性之间的关联。发现24小时浓度-时间曲线下面积/最低抑菌浓度（AUC0-24h/MIC）是抗菌活性的最佳指标。对于抑菌作用，血清、漏出液和渗出液中24小时的AUC0-24h/MIC值分别为0.27、0.17和0.14；对于杀菌活性，血清和渗出液中24小时的AUC0-24h/MIC值分别为3.76和5.31；对于细菌清除，血清值为18.46。这些发现为优化加米霉素给药方案以治疗牛多杀性巴氏杆菌引起的呼吸道疾病提供了有价值的见解。
