PDF(Pubmed)
Abstract：
Time-kill curves (TKCs) are more informative compared with the use of minimum inhibitory concentration (MIC) as they allow the capture of bacterial growth and the development of drug killing rates over time, which allows to compute key pharmacodynamic (PD) parameters. Our study aimed, using a semi-mechanistic mathematical model, to estimate the best pharmacokinetic/pharmacodynamic (PK/PD) indices (ƒAUC/MIC or %ƒT > MIC) for the prediction of clinical efficacy of veterinary FQs in Staphylococcus pseudintermedius, Staphylococcus aureus, and Escherichia coli collected from canine pyoderma cases with a focus on the comparison between marbofloxacin and pradofloxacin. Eight TCKs for each bacterial species (4 susceptible and 4 resistant) were analysed in duplicate. The best PK/PD index was ƒAUC24h/MIC in both staphylococci and E. coli. For staphylococci, values of 25-40 h were necessary to achieve a bactericidal effect, whereas the calculated values (25-35 h) for E. coli were lower than those predicting a positive clinical outcome (100-120 h) in murine models. Pradofloxacin showed a higher potency (lower EC50) in comparison with marbofloxacin. However, no difference in terms of a maximal possible pharmacological killing rate (Emax) was observed. Taking into account in vivo exposure at the recommended dosage regimen (3 and 2 mg/kg for pradofloxacin and marbofloxacin, respectively), the overall killing rates (Kdrug) computed were also similar in most instances.
摘要：
与使用最小抑制浓度（MIC）相比，时间杀伤曲线（TKCs）信息更丰富，因为它们可以捕获细菌生长并随着时间的推移发展药物杀伤率。它允许计算关键药效学(PD)参数。我们的研究旨在,使用半机械数学模型，为了估计最佳的药代动力学/药效学（PK/PD）指标（fAUC/MIC或％fT>MIC），以预测兽用FQs在假中间葡萄球菌中的临床疗效，金黄色葡萄球菌,和从犬脓皮病病例中收集的大肠杆菌，重点是马波沙星和普拉多沙星之间的比较。重复分析每种细菌物种的8个TCK(4个易感和4个抗性)。葡萄球菌和大肠杆菌的PK/PD指数均为fAUC24h/MIC。对于葡萄球菌，25-40小时的值是达到杀菌效果所必需的，而大肠杆菌的计算值（25-35小时）低于小鼠模型中预测阳性临床结果（100-120小时）的值。与马波沙星相比，普拉氧氟沙星显示出更高的效力（更低的EC50）。然而,在最大可能的药理杀伤率（Emax）方面没有观察到差异。考虑到推荐剂量方案下的体内暴露（普拉氧氟沙星和马波沙星分别为3和2mg/kg，分别)，在大多数情况下,计算的总杀伤率(Kdrug)也相似.
