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 Escherichia coli (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 (AUC0-12) 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.

中文翻译：

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通过犬离体模型研究磷霉素对抗产广谱 β-内酰胺酶的大肠杆菌的尿药代动力学和药效学特征：一项初步研究。


磷霉素是治疗超广谱 β-内酰胺酶 (ESBL) 细菌的候选药物，但其功效尚未在狗身上进行研究。本研究调查了六只健康犬口服 80 mg/kg 磷霉素的尿药代动力学/药效学 (PK/PD) 曲线，以评估其对产 ESBL 细菌引起的犬尿路感染 (UTI) 的疗效。使用四种产 ESBL 大肠杆菌 (ESBL-EC)，其磷霉素最低抑制浓度 (MIC) 分别为 0.5、1、2 和 32 µg/mL。给药后获取尿样用于测量尿药物浓度和尿杀菌滴度（UBT）。给药后0-4、4-8和8-12小时的尿浓度（μg/mL，平均值±SE）分别为1348.2±163.5、1191.6±260.2和661.1±190.4。磷霉素试验期间的平均尿曲线下面积（AUC0-12）估计为12,803.8 µg·h/mL。测试期间所有测试菌株的UBT均随尿液浓度波动密切（r = 0.944-1.000），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，磷霉素 80 mg/kg 每日两次可能适合治疗 ESBL-EC 引起的 MIC ≤ 128 µg/mL 的犬尿路感染。