Department of Anesthesiology, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany.
Eurofins Laborbetriebsgesellschaft Gelsenkirchen GmbH, Gelsenkirchen, Germany.
Sci Rep. 2021 Jun 8;11(1):12032. doi: 10.1038/s41598-021-91423-9.
To assess fosfomycin (FOS) elimination in patients with sepsis and acute kidney injury (AKI) undergoing slow-extended daily dialysis (SLEDD) with the Genius system in a prospective observational study. After ethics committee approval ten patients with sepsis and AKI stage 3 underwent daily SLEDD sessions of eight hours. FOS was applied i.v. at doses of 3 × 5 g per day. FOS serum levels were measured pre- and post hemofilter before, during, and after SLEDD sessions, and instantaneous clearance was calculated. In five of the patients, we analyzed FOS levels after the first dose, in the other five patients serum levels were measured during ongoing therapy. FOS was eliminated rapidly via the hemofilter. FOS clearance decreased from 152 ± 10 mL/min (start of SLEED session) to 43 ± 38 mL/min (end of SLEDD session). In 3/5 first-dose patients after 4-6 h of SLEDD the FOS serum level fell below the EUCAST breakpoint of 32 mg/L for Enterobacterales and Staphylococcus species. In all patients with ongoing fosfomycin therapy serum levels were high and above the breakpoint at all times. FOS toxicity or adverse effects were not observed. FOS serum concentrations exhibit wide variability in critically ill patients with sepsis and AKI. FOS is eliminated rapidly during SLEDD. A loading dose of 5 g is not sufficient to achieve serum levels above the EUCAST breakpoint for common bacteria in all patients, considering that T > MIC > 70% of the dosing interval indicates sufficient plasma levels. We thus recommend a loading dose of 8 g followed by a maintenance dose of 5 g after a SLEDD session in anuric patients. We strongly recommend therapeutic drug monitoring of FOS levels in critically ill patients with AKI and dialysis therapy.
在一项前瞻性观察研究中，评估 Genius 系统下脓毒症和急性肾损伤（AKI）患者行缓慢延长每日透析（SLEDD）时磷霉素（FOS）的消除情况。在伦理委员会批准后，10 名脓毒症和 AKI 第 3 期患者进行了 8 小时的每日 SLEDD 治疗。FOS 静脉内给药剂量为每天 3×5 g。在 SLEDD 治疗前后、治疗期间和治疗后，在血液滤器前和血液滤器后测量 FOS 血清水平，并计算瞬时清除率。在 5 名患者中，我们分析了首剂后的 FOS 水平，在另外 5 名患者中，在持续治疗期间测量了血清水平。FOS 快速通过血液滤器清除。FOS 清除率从 SLEED 治疗开始时的 152±10 mL/min 下降到 SLEDD 治疗结束时的 43±38 mL/min。在 5 名首剂患者中，有 3 名患者在 SLEDD 治疗 4-6 小时后，FOS 血清水平降至肠杆菌科和葡萄球菌属的 EUCAST 截断值 32 mg/L 以下。在所有接受磷霉素治疗的患者中，血清水平始终较高且高于截断值。未观察到 FOS 毒性或不良反应。FOS 血清浓度在脓毒症和 AKI 的危重症患者中表现出很大的变异性。FOS 在 SLEDD 期间迅速消除。对于所有患者，考虑到 T>MIC>70%的给药间隔表明足够的血浆水平，负荷剂量 5 g 不足以使血清水平达到 EUCAST 常见细菌的截断值。因此，我们建议在无尿患者中，SLEDD 治疗后给予负荷剂量 8 g，随后给予维持剂量 5 g。我们强烈建议对接受 AKI 和透析治疗的危重症患者进行 FOS 水平的治疗药物监测。
