Department of Pharmacology, Riga Stradins University, Riga, Latvia.
Department of Biology and Microbiology, Riga Stradins University, Riga, Latvia.
J Vet Pharmacol Ther. 2023 Sep;46(5):332-343. doi: 10.1111/jvp.13383. Epub 2023 Apr 15.
Levofloxacin veterinary formulations are available in Argentina, China and India for the use in dogs, cattle, pig and sheep, but not currently in the rabbit. Only the extra-label use in rabbits is possible. Levofloxacin is not labelled for veterinary use in the EU or the USA. The activity of levofloxacin against rabbit pathogens Pasteurella multocida (P. multocida) and Escherichia coli (E. coli) was evaluated. Minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined in broth and serum for 10 P. multocida isolates and 5 E. coli isolates from rabbits. One isolate of each bacterial species was used for the time-killing curve study in vitro and ex vivo. In vitro AUC /MIC ratios were used for building the inhibitory pharmacodynamic I model. The P. multocida MIC were 0.008-0.5 μg/mL, MBC - 0.015-0.5 μg/mL. Escherichia coli MIC was 0.008-0.03 μg/mL and MBC - 0.03-0.25 μg/mL. Bacterial counts were reduced to the limit of detection after 24 h with levofloxacin concentrations of 2 MIC and higher. All serum samples from rabbits treated with levofloxacin eliminated the bacteria within 24 h. AUC /MIC ratios for bacteriostatic, bactericidal and bacterial elimination effects for P. multocida and E. coli isolates were 21, 29 and 75 h and 27, 32 and 60 h, respectively. Proposed daily doses against P. multocida (MIC = 0.015 μg/mL) and E. coli (MIC = 0.03 μg/mL) isolates were calculated as ≤0.91 and ≤1.43 mg/kg, respectively. Fluoroquinolones are categorized by WHO as 'highest priority critically important antimicrobials'. Considering the increasing importance of antimicrobial stewardship, antimicrobials from a lower importance category that are active against the isolate of interest should be used in preference to fluoroquinolones. Fluoroquinolone use in veterinary medicine should be based on antimicrobial susceptibility testing in order to mitigate the risk to public health and prevent the spread of bacterial resistance.
左氧氟沙星兽用制剂在阿根廷、中国和印度可用于犬、牛、猪和羊，但目前在兔中不可用。仅允许标签外用于兔。左氧氟沙星在欧盟或美国未被标记用于兽医用途。评估了左氧氟沙星对兔病原体多杀巴斯德菌（P. multocida）和大肠杆菌（E. coli）的活性。在肉汤和血清中测定了 10 株多杀巴斯德菌分离株和 5 株来自兔的大肠杆菌分离株的最小抑菌浓度（MIC）和最小杀菌浓度（MBC）。每种细菌的一个分离株用于体外和体内时间杀伤曲线研究。体外 AUC/MIC 比值用于构建抑制性药效动力学 I 模型。多杀巴斯德菌 MIC 为 0.008-0.5μg/ml，MBC 为 0.015-0.5μg/ml。大肠杆菌 MIC 为 0.008-0.03μg/ml，MBC 为 0.03-0.25μg/ml。用左氧氟沙星浓度 2MIC 及更高浓度处理后，24 小时内细菌计数降至检测限以下。用左氧氟沙星治疗的所有兔血清样本在 24 小时内消除了细菌。多杀巴斯德菌和大肠杆菌分离株的抑菌、杀菌和细菌消除作用的 AUC/MIC 比值分别为 21、29 和 75h 和 27、32 和 60h。针对多杀巴斯德菌（MIC=0.015μg/ml）和大肠杆菌（MIC=0.03μg/ml）分离株的推荐日剂量计算为≤0.91 和≤1.43mg/kg。氟喹诺酮类药物被世界卫生组织列为“最高优先级的重要抗菌药物”。考虑到抗菌药物管理的重要性日益增加，应优先使用对感兴趣的分离株有效的来自较低重要性类别的抗菌药物，而不是氟喹诺酮类药物。兽医中使用氟喹诺酮类药物应基于抗菌药物敏感性测试，以减轻对公共健康的风险并防止细菌耐药性的传播。
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