School of Life Science and Engineering, Foshan University, Foshan, China.
Laboratory Animal Center, Peking University Shenzhen Graduate School, Shenzhen, China.
J Vet Pharmacol Ther. 2024 Nov;47(6):503-511. doi: 10.1111/jvp.13475. Epub 2024 Aug 12.
Mycoplasma synoviae (MS) infection is a serious threat to poultry industry in China. Tilmicosin is a semisynthetic macrolide antibiotic used only in animals and has shown potential efficacy against MS, but there were no reported articles concerning the pharmacokinetics/pharmacodynamics (PK/PD) interactions of tilmicosin against MS in vitro and vivo. This study aimed to assess the antibacterial activity of tilmicosin against MS in vitro and in vivo using PK/PD model to provide maximal efficacy. The minimum inhibitory concentration (MIC) and killing rates of different drug concentrations were measured using the microdilution method in vitro. Then, tilmicosin was administered orally to the MS-infected chickens at doses of 7.5 and 60 mg/kg, and the PK parameters of tilmicosin in joint dialysates were determined using high-pressure liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) combined with the microdialysis technique. The antibacterial effect (△E) was calculated when the infected chickens were administered a single oral dose of tilmicosin at 4, 7.5, 15, 30, and 60 mg/kg b.w. The PK and PD data were fitted using the Sigmoid E model to evaluate the PK/PD interactions of tilmicosin against MS. The bactericidal activity of tilmicosin against MS was concentration dependent. Furthermore, the PK/PD index of AUC/MIC exhibited the most optimal fitting results (R = .98). The MS load decreased by 1, 2, and 3 Log CFU/mL, then AUC/MIC was determined as 13.99, 20.53, and 28.23 h, respectively, and the bactericidal effect can be achieved when the dose of MS-infected chickens is at 31.64 mg/kg b.w. The findings of this study hold significant implications for optimizing the treatment regimen for MS infection.
滑液支原体（MS）感染是中国禽类养殖业的严重威胁。替米考星是一种仅用于动物的半合成大环内酯类抗生素，已显示出对 MS 的潜在疗效，但尚未有报道探讨替米考星在体内外对 MS 的药代动力学/药效学（PK/PD）相互作用。本研究旨在通过 PK/PD 模型评估替米考星对 MS 的体外和体内抗菌活性，以提供最大疗效。采用微量稀释法在体外测定不同药物浓度的最小抑菌浓度（MIC）和杀菌率。然后，将替米考星以 7.5 和 60mg/kg 的剂量口服给药给 MS 感染的鸡，并用高效液相色谱/串联质谱（HPLC-MS/MS）结合微透析技术测定关节透析液中的替米考星 PK 参数。当感染鸡单次口服 4、7.5、15、30 和 60mg/kg bw 的替米考星时，计算抗菌效果（△E）。采用 Sigmoid E 模型拟合 PK 和 PD 数据，评估替米考星对 MS 的 PK/PD 相互作用。替米考星对 MS 的杀菌活性呈浓度依赖性。此外，AUC/MIC 的 PK/PD 指数表现出最佳拟合结果（R=.98）。当 AUC/MIC 分别为 13.99、20.53 和 28.23 h 时，MS 负荷分别降低 1、2 和 3 Log CFU/mL，当 MS 感染鸡的剂量为 31.64mg/kg bw 时，可以达到杀菌效果。本研究结果对优化 MS 感染的治疗方案具有重要意义。
