Wang Hongjuan, Zhang Longfei
College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China.
Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.
Front Vet Sci. 2024 Jul 3;11:1407907. doi: 10.3389/fvets.2024.1407907. eCollection 2024.
(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.
The 99% minimum inhibitory concentration (MIC) 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 E model was used to analyze the relationships between PK/PD parameters and antibacterial effects.
The values of MIC, MIC, 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 Log CFU/mL, respectively). The MIC of APP increased 32-fold at 8 MIC. AUC/MIC had the best fit with the antibacterial effect ( = 0.9867). The AUC/MIC 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.
副猪嗜血杆菌（APP）是一种严重影响家畜养殖发展的病原体。由于抗菌药物的过度使用，许多多重耐药菌出现并传播，对畜牧业构成了威胁。因此，我们建立了蠕动泵感染模型（PPIM），以评估在突变选择窗（MSW）期间，泰拉霉素对APP的敏感性变化以及药代动力学/药效学（PK/PD）整合情况，以预防耐药突变菌的出现。
采用琼脂平板法测定泰拉霉素对APP的99%最低抑菌浓度（MIC）和突变预防浓度（MPC）。根据肺部泰拉霉素数据建立动态感染模型后，给予不同剂量使药物浓度处于MSW的不同部位。监测APP的菌量和敏感性。通过高效液相色谱-串联质谱法测定泰拉霉素浓度。最后，使用S型E模型分析PK/PD参数与抗菌效果之间的关系。
泰拉霉素对APP的MIC、MIC和MPC值分别为2、1.4和44.8μg/mL。PPIM稳定。在5.6至44.8μg/mL（分别为-4.48至-7.05 Log CFU/mL）观察到无再生长的清除效果。在8倍MIC时，APP的MIC增加了32倍。AUC/MIC与抗菌效果拟合最佳（r = 0.9867）。实现抑菌、杀菌和清除效果所需的AUC/MIC分别为1.80、87.42和198小时。我们的结果可为泰拉霉素临床治疗APP感染提供指导，并避免耐药菌的产生。
