Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, IL, USA Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA.
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
J Antimicrob Chemother. 2015 Jul;70(7):2068-73. doi: 10.1093/jac/dkv067. Epub 2015 Mar 22.
As the optimal administration time for fosfomycin peri-procedural prophylaxis is unclear, we sought to determine optimal administration times for fosfomycin peri-procedural prophylaxis.
Plasma, peripheral zone and transition zone fosfomycin concentrations were obtained from 26 subjects undergoing transurethral resection of the prostate (TURP), following a single oral dose of 3 g of fosfomycin. Population pharmacokinetic modelling was completed with the Nonparametric Adaptive Grid (NPAG) algorithm (Pmetrics package for R), with a four-compartment model. Plasma and tissue concentrations were simulated during the first 24 h post-dose, comparing these with EUCAST susceptibility breakpoints for Escherichia coli, a common uropathogen.
Non-compartmental-determined pharmacokinetic values in our population were similar to those reported in the package insert. Predicted plasma concentrations rapidly increased after the first hour, giving more than 90% population coverage for organisms with an MIC ≤4 mg/L over the first 12 h post-dose. Organisms with higher MICs fared much worse, with organisms at the EUCAST breakpoint being covered for <10% of the population at any time. Transitional zone prostate concentrations exceeded 4 mg/L for 90% of the population between hours 1 and 9. Peripheral zone prostate concentrations were much lower and only exceeded 4 mg/L for 70% of the population between hours 1 and 4.
Until more precise plasma and tissue data are available, we recommend that fosfomycin prophylaxis be given 1-4 h prior to prostate biopsy. We do not recommend fosfomycin prophylaxis for subjects with known organisms with MICs >4 mg/L.
由于磷霉素术前预防的最佳给药时间尚不清楚，我们旨在确定磷霉素术前预防的最佳给药时间。
在 26 例行经尿道前列腺切除术（TURP）的患者中，单次口服 3 g 磷霉素后，我们获得了血浆、外周区和移行区的磷霉素浓度。采用非参数自适应网格（NPAG）算法（R 中的 Pmetrics 包）进行群体药代动力学建模，采用四室模型。模拟了首次给药后 24 小时内的血浆和组织浓度，并将这些浓度与常见尿路病原体大肠埃希菌的 EUCAST 药敏折点进行了比较。
我们人群中的非房室药代动力学值与说明书中的值相似。预测的血浆浓度在首次给药后 1 小时内迅速升高，在首次给药后 12 小时内，超过 90%的人群对 MIC≤4mg/L 的细菌具有 90%的覆盖率。MIC 较高的细菌情况则更差，EUCAST 折点的细菌在任何时间的覆盖率均<10%。在 1 至 9 小时之间，90%的人群的移行区前列腺浓度超过 4mg/L。外周区前列腺浓度则低得多，只有 70%的人群在 1 至 4 小时之间的浓度超过 4mg/L。
在获得更精确的血浆和组织数据之前，我们建议在前列腺活检前 1-4 小时给予磷霉素预防。对于已知 MIC>4mg/L 的细菌，我们不建议使用磷霉素预防。
