■胸膜肺炎放线杆菌(APP)是一种严重的病原体,会影响畜牧业的发展。由于过度使用抗菌药物,许多多重耐药细菌已经出现并传播,威胁到畜牧业。因此,我们建立了蠕动泵感染模型(PPIM),以评估突变选择窗(MSW)期间泰拉霉素对APP的敏感性变化和药代动力学/药效学(PK/PD)整合,以防止突变耐药菌的出现.
■使用琼脂平板法测量了泰拉霉素对APP的99%最小抑制浓度(MIC99)和突变预防浓度(MPC)。在基于肺部的tulatromycin数据建立动态感染模型后,给药不同剂量使药物浓度位于MSW的不同部位。监测APP的人群和敏感性。通过高效液相色谱-串联质谱法测量泰拉霉素浓度。最后,采用S型Emax模型分析PK/PD参数与抗菌作用的关系。
■MIC的值,MIC99和Tulathromycin对APP的MPC分别为2、1.4和44.8μg/mL,分别。PPIM是稳定的。在5.6至44.8μg/mL(-4.48至-7.05Log10CFU/mL,分别)。APP的MIC在8MIC99时增加32倍。AUC168h/MIC99与抗菌效果拟合最好(R2=0.9867)。实现抑菌所需的AUC168h/MIC99,杀菌,清除效果分别为1.80、87.42和198h,分别。本研究结果可为临床应用泰拉霉素治疗APP感染、避免耐药菌的产生提供指导。
UNASSIGNED: Actinobacillus pleuropneumoniae (APP) is a serious pathogen that affects the development of livestock breeding. Due to excessive use of antimicrobial drugs, many multidrug-resistant bacteria have emerged and spread, which have threatened the livestock industry. Therefore, we established a peristaltic pump infection model (PPIM) to evaluate the susceptibility change and pharmacokinetic/pharmacodynamic (PK/PD) integration of tulathromycin against APP during the mutant selection window (
MSW) for preventing the emergence of mutant-resistant bacteria.
UNASSIGNED: The 99% minimum inhibitory concentration (MIC99) and mutant prevention concentration (MPC) of tulathromycin against APP were measured using the agar-plate method. After the model of dynamic infection had been established based on tulathromycin data in lungs, different dosages were administered to make the drug concentrations located in different parts of the
MSW. The population and sensitivity of APP were monitored. Tulathromycin concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Finally, a sigmoid Emax model was used to analyze the relationships between PK/PD parameters and antibacterial effects.
UNASSIGNED: The values of MIC, MIC99, and MPC of tulathromycin against APP were 2, 1.4, and 44.8 μg/mL, respectively. The PPIM was stable. An elimination effect without regrowth was observed at 5.6 to 44.8 μg/mL (-4.48 to -7.05 Log10 CFU/mL, respectively). The MIC of APP increased 32-fold at 8 MIC99. AUC168 h/MIC99 had the best fit with the antibacterial effect (R 2 = 0.9867). The AUC168 h/MIC99 required to achieve bacteriostatic, bactericidal, and clearance effects were 1.80, 87.42, and 198 h, respectively. Our results could provide guidance for the clinical application of tulathromycin to treat APP infection and avoid the generation of drug-resistant bacteria.