Department of Internal Medicine, Haga Teaching Hospital, The Hague, The Netherlands.
Centre for Human Drug Research (CHDR), Leiden, The Netherlands.
J Antimicrob Chemother. 2020 Nov 1;75(11):3278-3285. doi: 10.1093/jac/dkaa294.
To evaluate the pharmacokinetics and clinical effectiveness of IV and oral fosfomycin treatment in patients with recurrent urinary tract infection (rUTI) with Escherichia coli.
Patients with rUTI treated with 3 g of oral fosfomycin every 72 h for at least 14 days were included in a prospective open-label single-centre study. Serum samples were taken after oral and IV administration of fosfomycin. Urine was collected for 24 h on 3 consecutive days. Fosfomycin concentrations in serum and urine were analysed using validated LC-MS/MS. Pharmacokinetics were evaluated using a population model. EudraCT number 2018-000616-25.
Twelve patients were included, of whom nine were also administered IV fosfomycin. Data were best described by a two-compartment model with linear elimination and a transit-absorption compartment. Median values for absolute bioavailability and serum half-life were 18% and 2.13 h, respectively. Geometric mean urine concentrations on Days 1, 2 and 3 were above an MIC of 8 mg/L after both oral and IV administration. Quality of life reported on a scale of 1-10 increased from 5.1 to 7.4 (P = 0.001). The average score of UTI symptoms decreased after fosfomycin dosing (by 3.1 points, 95% CI = -0.7 to 7.0, P = 0.10).
Oral fosfomycin at 3 g every 72 h provides plasma and urine concentrations of fosfomycin above the MIC for E. coli. This pharmacokinetic model can be used to develop optimal dosing regimens of fosfomycin in patients with UTI.
评估磷霉素静脉和口服治疗大肠埃希菌复发性尿路感染（rUTI）患者的药代动力学和临床疗效。
将接受至少 14 天 3g 口服磷霉素，每 72 小时一次治疗的 rUTI 患者纳入前瞻性开放标签单中心研究。在口服和静脉给予磷霉素后采集血清样本。连续 3 天采集 24 小时尿液。使用验证后的 LC-MS/MS 分析血清和尿液中的磷霉素浓度。使用群体模型评估药代动力学。EudraCT 编号 2018-000616-25。
纳入了 12 名患者，其中 9 名患者还接受了静脉磷霉素治疗。数据最好用具有线性消除和转运吸收室的两室模型来描述。绝对生物利用度和血清半衰期的中位数分别为 18%和 2.13 小时。口服和静脉给药后第 1、2 和 3 天的尿液浓度几何平均值均高于 8mg/L 的 MIC。报告的生活质量评分从 1-10 增加到 7.4（P=0.001）。磷霉素给药后，尿路感染症状的平均评分降低（降低 3.1 分，95%CI=-0.7 至 7.0，P=0.10）。
磷霉素 3g 每 72 小时口服给药可提供高于大肠埃希菌 MIC 的磷霉素血浆和尿液浓度。该药代动力学模型可用于为尿路感染患者制定最佳的磷霉素给药方案。
