Evaluation the kill rate and mutant selection window of danofloxacin against Actinobacillus pleuropneumoniae in a peristaltic pump model

文献类型： 外文期刊

第一作者： Wang, Hongjuan

作者： Wang, Hongjuan;Liao, Chengshui;Ding, Ke;Zhang, Longfei;Wang, Lei;Wang, Hongjuan;Liao, Chengshui;Ding, Ke;Wang, Lei

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关键词： Actinobacillus pleuropneumoniae; Kill rate; Mutation selection window; Peristaltic pump model; PK/PD integration

期刊名称：BMC VETERINARY RESEARCH （ 影响因子：2.6； 五年影响因子：2.9 ）

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年卷期： 2024 年 20 卷 1 期

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收录情况： SCI

摘要： Background Actinobacillus pleuropneumoniae is a serious pathogen in pigs. The abundant application of antibiotics has resulted in the gradual emergence of drugresistant bacteria, which has seriously affected treatment of disease. To aid measures to prevent the emergence and spread of drug-resistant bacteria, herein, the kill rate and mutant selection window (MSW) of danofloxacin (DAN) against A. pleuropneumoniae were evaluated. Methods For the kill rate study, the minimum inhibitory concentration (MIC) was tested using the micro dilution broth method and time-killing curves of DAN against A. pleuropneumoniae grown in tryptic soy broth (TSB) at a series drug concentrations (from 0 to 64 MIC) were constructed. The relationships between the kill rate and drug concentrations were analyzed using a Sigmoid E-max model during different time periods. For the MSW study, the MIC99 (the lowest concentration that inhibited the growth of the bacteria by >= 99%) and mutant prevention concentration (MPC) of DAN against A. pleuropneumoniae were measured using the agar plate method. Then, a peristaltic pump infection model was established to simulate the dynamic changes of DAN concentrations in pig lungs. The changes in number and sensitivity of A. pleuropneumoniae were measured. The relationships between pharmacokinetic/pharmacodynamic parameters and the antibacterial effect were analyzed using the Sigmoid E-max model. Results In kill rate study, the MIC of DAN against A. pleuropneumoniae was 0.016 mu g/mL. According to the kill rate, DAN exhibited concentration-dependent antibacterial activity against A. pleuropneumoniae. A bactericidal effect was observed when the DAN concentration reached 4-8 MIC. The kill rate increased constantly with the increase in DAN concentration, with a maximum value of 3.23 Log(10) colony forming units (CFU)/mL/h during the 0-1 h period. When the drug concentration was in the middle part of the MSW, drugresistant bacteria might be induced. Therefore, the dosage should be avoided to produce a mean value of AUC(24h)/MIC99 (between 31.29 and 62.59 h. The values of AUC(24h)/MIC99 to achieve bacteriostatic, bactericidal, and eradication effects were 9.46, 25.14, and > 62.59 h, respectively. Conclusion These kill rate and MSW results will provide valuable guidance for the use of DAN to treat A. pleuropneumoniae infections.

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