Assessment of urinary pharmacokinetic and pharmacodynamic profiles of faropenem against extended-spectrum β-lactamaseproducing Escherichia coli with canine ex vivo modelling: a pilot study
Assessment of urinary pharmacokinetic and pharmacodynamic profiles of faropenem against extended-spectrum β-lactamaseproducing Escherichia coli with canine ex vivo modelling: a pilot study
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通过犬离体模型评估法罗培南对抗产广谱 β-内酰胺酶大肠杆菌的尿药代动力学和药效学特征：一项初步研究
DOI：
10.1099/acmi.0.000004
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发表时间：
2019
影响因子：
--
通讯作者：
Naoki Miyashita and Yoshiaki Hikasa
中科院分区：
文献类型：
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作者：
Kazuki Harada;Takae Shimizu;Naoki Miyashita and Yoshiaki Hikasa
本研究旨在研究6只健康犬经口给予5 mg kg− 1法罗培南的尿液药代动力学和药效学，以评估药物对产超广谱β-内酰胺酶（ESBL）细菌的犬尿路感染（UTI）的疗效。使用了6株产ESBL-EC的大肠埃希菌（ESBL-EC），其法罗培南最低抑菌浓度（MIC）如下：1 µg ml−1（n =2）、2 µg ml−1（n=2）、4 µg ml−1（n=1）和16 µg ml−1（n=1）。在给药后的前12小时内，每4小时采集一次尿液样本，以测量尿液药物浓度和尿液杀菌滴度（UBT）。尿中法罗培南浓度和UBT均在给药后0-4 h达到高峰，8-12 h明显下降。法罗培南在8-12 h的平均尿药浓度（23±5.2 µg ml−1）超过MIC 1 µg ml− 1的4倍，这是抑制90% ESBL-EC生长所需的。 这些结果表明，法罗培南以5 mg kg− 1的剂量每日两次给药对于治疗大多数ESBL-EC相关UTI犬是可接受的。
This study was carried out to investigate the urinary pharmacokinetics and pharmacodynamics of faropenem administered orally at 5 mg kg−1in six healthy dogs to assess the efficacy of the drug for canine urinary tract infections (UTIs) with extended-spectrumβ-lactamase (ESBL)-producing bacteria. Six strains of ESBL-producingEscherichia coli(ESBL-EC) with the following faropenem minimum inhibitory concentrations (MICs) were used: 1 µg ml−1(n=2), 2 µg ml−1(n=2), 4 µg ml−1(n=1) and 16 µg ml−1(n=1). Urine samples were obtained every 4 h for the first 12 h after administration to measure urinary drug concentration and urinary bactericidal titres (UBTs). Both the urine concentration of faropenem and the UBTs for all tested strains peaked at 0–4 h after administration, and decreased markedly at 8–12 h. The mean urinary concentration of faropenem at 8–12 h (23±5.2 µg ml−1) exceeded the MIC of 1 µg ml−1by fourfold, which is required to inhibit the growth of 90 % of ESBL-EC. These findings indicate that faropenem administered twice daily at a dose of 5 mg kg−1is acceptable for the treatment of most dogs with ESBL-EC-related UTIs.