Harada Kazuki, Shimizu Takae, Kawaguchi Koji, Furuhashi Takeshi, Ishihara Genki
Department of Veterinary Internal Medicine, Tottori University, Tottori 680-8553, Japan.
Anicom Specialty Medical Institute Inc., Kanagawa 231-0033, Japan.
Antibiotics (Basel). 2020 May 5;9(5):230. doi: 10.3390/antibiotics9050230.
Fosfomycin is a candidate drug for extended-spectrum β-lactamase (ESBL)-producing bacteria, but its efficacy is yet to be investigated in dogs. This study investigated the urinary pharmacokinetic/pharmacodynamic (PK/PD) profile of fosfomycin orally administered at 80 mg/kg to six healthy dogs to assess its efficacy for canine urinary tract infections (UTIs) caused by ESBL-producing bacteria. Four strains of ESBL-producing (ESBL-EC) characterized by fosfomycin minimum inhibitory concentrations (MICs) of 0.5, 1, 2, and 32 µg/mL were used. Urine samples for the measurement of urinary drug concentrations and urinary bactericidal titers (UBTs) were obtained after drug administration. The urinary concentrations (µg/mL, mean ± SE) were 1348.2 ± 163.5, 1191.6 ± 260.2, and 661.1 ± 190.4 at 0-4, 4-8, and 8-12 h, respectively, after drug administration. The mean urinary area under the curve during the test period (AUC) of fosfomycin was estimated to be 12,803.8 µg·h/mL. The UBTs for all tested strains fluctuated closely with urine concentration during the test period (r = 0.944-1.000), and the area under the UBT-versus-time curve correlated with the urinary AUC/MIC of each strain (r = 0.991). According to the optimal urinary PK/PD target value, fosfomycin at 80 mg/kg twice daily may be suitable for the treatment of canine UTIs caused by ESBL-EC presenting MIC ≤ 128 µg/mL.
磷霉素是一种针对产超广谱β-内酰胺酶（ESBL）细菌的候选药物，但尚未在犬类中研究其疗效。本研究调查了6只健康犬口服80mg/kg磷霉素后的尿药代动力学/药效学（PK/PD）特征，以评估其对由产ESBL细菌引起的犬尿路感染（UTI）的疗效。使用了4株磷霉素最低抑菌浓度（MIC）分别为0.5、1、2和32μg/mL的产ESBL大肠杆菌（ESBL-EC）菌株。给药后采集尿液样本用于测量尿药浓度和尿杀菌效价（UBT）。给药后0-4、4-8和8-12小时的尿浓度（μg/mL，均值±标准误）分别为1348.2±163.5、1191.6±260.2和661.1±190.4。磷霉素在测试期间的尿药曲线下面积（AUC）估计为12803.8μg·h/mL。所有测试菌株的UBT在测试期间与尿浓度密切波动（r = 0.944-1.000）,且UBT-时间曲线下面积与各菌株的尿AUC/MIC相关（r = 0.991）。根据最佳尿PK/PD目标值，每日两次80mg/kg的磷霉素可能适用于治疗由MIC≤128μg/mL的ESBL-EC引起的犬UTI。
