Shimizu Takae, Harada Kazuki, Manabe Saki, Tsukamoto Taku, Ito Norihiko, Hikasa Yoshiaki
The United Graduate School of Veterinary Science, Yamaguchi University, 1677-1, Yoshida, Yamaguchi 753-8511, Japan.
Joint Department of Veterinary Medicine, Tottori University, Minami 4-101, Koyama-Cho, Tottori 680-8553, Japan.
J Med Microbiol. 2017 May;66(5):616-621. doi: 10.1099/jmm.0.000476. Epub 2017 May 4.
The aim of this study was to investigate the urinary pharmacokinetics (PK) of orbifloxacin (OBFX) administered at 5 mg kg-1 in six healthy dogs. A further aim was to use an ex vivo model to evaluate the urinary PK and pharmacodynamics (PD) of OBFX to determine its urinary bactericidal titre (UBT), which represents the maximal dilution of urine allowing bactericidal activity.
Fourteen urinary tract infection (UTI) pathogenic strains of five bacterial species (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis and Staphylococcuspseudintermedius) were used. Urine samples were obtained every 4 h for the first 24 h after OBFX administration, for measurement of urine drug concentration and UBT.Results/Key findings. The urine OBFX concentration peaked at 0-4, 4-8 or 4-8 h after administration, with a maximum concentration of 383±171 µg ml-1. Overall, the fluctuation in median UBT closely correlated with that of the mean urine OBFX concentration. In addition, the median areas under the UBT-time curves (AUBTs) were significantly inversely correlated with the MICs for OBFX in the tested strains (P<0.01). Notably, median UBTs and AUBTs were extremely low (0-0.5 and 2-5, respectively) in OBFX-resistant E. coli strains with MIC ≥8 µg ml-1.
The fluctuation of UBTs closely correlated with that of urine concentration, and UBT values depended on the susceptibility of the bacterial strains to OBFX. We believe that ex vivo modelling to determine UBTs is useful to evaluate the urinary PK/PD of antimicrobials indicated for UTIs in dogs.
本研究旨在调查6只健康犬以5 mg kg-1剂量给予奥比沙星（OBFX）后的尿药代动力学（PK）。另一目的是使用体外模型评估OBFX的尿PK和药效学（PD），以确定其尿杀菌效价（UBT），即允许杀菌活性的尿液最大稀释度。
使用了5种细菌（大肠杆菌、铜绿假单胞菌、肺炎克雷伯菌、奇异变形杆菌和中间葡萄球菌）的14株尿路感染（UTI）致病菌株。在给予OBFX后的前24小时内，每4小时采集一次尿液样本，用于测量尿药浓度和UBT。结果/主要发现。尿OBFX浓度在给药后0-4、4-8或4-8小时达到峰值，最高浓度为383±171 µg ml-1。总体而言，UBT中位数的波动与尿OBFX平均浓度的波动密切相关。此外，UBT-时间曲线下的中位数面积（AUBT）与受试菌株中OBFX的最低抑菌浓度（MIC）呈显著负相关（P<0.01）。值得注意的是，在MIC≥8 µg ml-1的耐OBFX大肠杆菌菌株中，UBT中位数和AUBT极低（分别为0-0.5和2-5）。
UBT的波动与尿液浓度的波动密切相关，UBT值取决于细菌菌株对OBFX的敏感性。我们认为，通过体外模型确定UBT有助于评估用于犬UTI的抗菌药物的尿PK/PD。
