Mycoplasma hyopneumoniae is the major pathogen of enzootic pneumonia in pigs. We established an in vitro dynamic model to investigate the relationship between the pharmacokinetic and pharmacodynamic (PK-PD) parameters of tiamulin against M. hyopneumoniae. Static time-killing curves showed that mycoplasmacidal activity (reduced 3.0 log10 (CFU/mL)) was achieved during 48 h when the drug concentration was 8 MIC, and with a maximum kill rate of 0.072/h. In dynamic time-killing studies, only the dose-fractionated regimen achieved mycoplasmacidal activity when drug concentration was 1.44 and 1.92 mg/L. The duration of post antibiotic effect (PAE) at 1 × MIC was 6.27 ± 0.11 h, and prolonged as the concentration of tiamulin increased. The cumulative percentage of time over a 48-h period that the drug concentration exceeds the MIC (%T > MIC) was the best PK-PD parameter to predict the antimicrobial activity of tiamulin against M. hyopneumoniae (R2 = 0.98). Tiamulin showed time-dependent and prolonged PAE activity. Two strains of M. hyopneumoniae (M1, M2) had acquired resistance to tiamulin as well as to valnemulin, tylosin and amikacin. The genome of strain ATCC 25934 was used as a reference for gene-mutation analysis. For strains M1 and M2, a A2058C mutation occurred in domain V of 23S rRNA. These data showed that tiamulin had excellent efficacy and concentration-dependent characteristics against M. hyopneumoniae in vitro. The lower dose was not safe because it could lead to enrichment of resistant bacteria.

中文翻译：

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体外动力学模型中头孢菌素对肺炎支原体的药代动力学-药效整合和耐药性。

猪肺炎支原体是猪内生性肺炎的主要病原体。我们建立了一个体外动力学模型，以研究替米林对猪肺炎支原体的药代动力学和药效学（PK-PD）参数之间的关系。静态时间杀灭曲线显示，当药物浓度为8 MIC时，在48小时内达到了支原体酸性活性（降低了3.0 log10（CFU / mL）），最大杀灭速率为0.072 / h。在动态时间杀灭研究中，当药物浓度为1.44和1.92 mg / L时，仅剂量分级方案可实现支原体酸活性。1×MIC时的抗生素后效应（PAE）持续时间为6.27±0.11 h，并且随着提穆林浓度的增加而延长。药物浓度超过MIC的48小时内的累积时间百分比（％T> MIC）是最好的PK-PD参数，可预测替米林对猪肺炎支原体的抗菌活性（R2 = 0.98）。钛蛋白显示出时间依赖性和延长的PAE活性。猪肺炎支原体的两个菌株（M1，M2）已获得了对噻菌灵以及缬氨菌素，泰乐菌素和丁胺卡那霉素的抗性。菌株ATCC 25934的基因组用作基因突变分析的参考。对于菌株M1和M2，A2058C突变发生在23S rRNA的结构域V中。这些数据表明，头孢菌素在体外对猪肺炎支原体具有优异的疗效和浓度依赖性。较低的剂量并不安全，因为它可能导致抗药性细菌的富集。猪肺炎支原体的两个菌株（M1，M2）已获得了对噻菌灵以及缬氨菌素，泰乐菌素和丁胺卡那霉素的抗性。菌株ATCC 25934的基因组用作基因突变分析的参考。对于菌株M1和M2，A2058C突变发生在23S rRNA的结构域V中。这些数据表明，头孢菌素在体外对猪肺炎支原体具有优异的疗效和浓度依赖性。较低的剂量并不安全，因为它可能导致耐药菌的富集。猪肺炎支原体的两个菌株（M1，M2）已获得了对噻菌灵以及缬氨菌素，泰乐菌素和丁胺卡那霉素的抗药性。菌株ATCC 25934的基因组用作基因突变分析的参考。对于菌株M1和M2，A2058C突变发生在23S rRNA的结构域V中。这些数据表明，头孢菌素在体外对猪肺炎支原体具有优异的疗效和浓度依赖性。较低的剂量并不安全，因为它可能导致抗药性细菌的富集。这些数据表明，头孢菌素在体外对猪肺炎支原体具有优异的疗效和浓度依赖性。较低的剂量并不安全，因为它可能导致抗药性细菌的富集。这些数据表明，头孢菌素在体外对猪肺炎支原体具有优异的疗效和浓度依赖性。较低的剂量并不安全，因为它可能导致耐药菌的富集。