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

Autor: Wang H; College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, 453003, China.; Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China., Liao C; College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, 453003, China.; The Key Lab of Veterinary Biological Products, Henan University of Science and Technology, Luoyang, 471000, China., Ding K; College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, 453003, China.; Laboratory of Functional Microbiology and Animal Health, Henan University of Science and Technology, Luoyang, 471023, China., Zhang L; College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, 453003, China. 1216591415@qq.com., Wang L; College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, 453003, China. wlei_007@163.com.; Institute of Farmland Irrigation, Chinese Academy of Agricultural Sciences, Xinxiang, 453003, China. wlei_007@163.com.
Jazyk: angličtina
Zdroj: BMC veterinary research [BMC Vet Res] 2024 Jun 03; Vol. 20 (1), pp. 241. Date of Electronic Publication: 2024 Jun 03.
DOI: 10.1186/s12917-024-04016-9
Abstrakt: 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 MIC 99 (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 µg/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 /MIC 99 (between 31.29 and 62.59 h. The values of AUC 24h /MIC 99 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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