Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
Institute of Clinical Pharmacology, Otto von-Guericke-University of Magdeburg, Magdeburg, Germany.
J Antimicrob Chemother. 2019 Apr 1;74(4):997-1002. doi: 10.1093/jac/dky511.
Owing to the emerging problem of MDR bacteria, interest in 'old' antibiotics such as colistin has re-emerged. However, research on the dosing of colistin in patients undergoing renal replacement therapy (RRT), such as prolonged intermittent renal replacement therapy (PIRRT), is scarce.
The aim of this study was to evaluate single- and multiple-dose pharmacokinetics of colistin and its prodrug colistin methanesulfonate in ICU patients with acute kidney injury (AKI) undergoing PIRRT.
We performed a prospective clinical pharmacokinetic single- and multiple-dose study. Eight ICU patients with AKI undergoing treatment with PIRRT and receiving intravenous colistin were studied on day 1 and days 5-9 of treatment, depending on the timing of dialysis. Six million IU (MIU) of colistin methanesulfonate was administered 8 h prior to the PIRRT session followed by 3 MIU every 8 h. The study was registered under clinicaltrails.gov (NCT02556190).
PIRRT removed a considerable amount of colistin and colistin methanesulfonate with a median dialyser plasma CL of 70.1 mL/min (IQR 36.6-96.2) for colistin and 69.3 mL/min (IQR 56.3-318.7) for colistin methanesulfonate. The median amount of colistin in the total collected dialysate was 154 mg (IQR 105-175), corresponding to about 50% of the daily dose. Median colistin peak concentrations accumulated from 5.79 mg/L (IQR 4.14-8.79) on day 1 to 9.49 mg/L (IQR 8.39-10.41) on days 5-9. Cmax was significantly and inversely correlated with body weight.
PIRRT eliminates about half of the daily administered colistin dose. Even a 6 MIU loading dose of colistin methanesulfonate may not ensure immediate sufficient colistin plasma levels in all critically ill patients. However, we measured significant colistin accumulation, suggesting that the dose of colistin methanesulfonate should be adjusted according to body weight and RRT intensity.
由于耐多药细菌这一新兴问题的出现，人们对多黏菌素等“老”抗生素重新产生了兴趣。然而，关于接受肾脏替代治疗（RRT）的患者（如长时间间歇性肾脏替代治疗（PIRRT））中多黏菌素剂量的研究却很少。
本研究旨在评估 ICU 中接受 PIRRT 的急性肾损伤（AKI）患者单次和多次给予多黏菌素及其前体多黏菌素甲磺酸盐的药代动力学。
我们进行了一项前瞻性临床药代动力学单次和多次剂量研究。8 例 ICU 中接受 AKI 治疗且正在接受 PIRRT 治疗的患者接受了研究，根据透析时机，在治疗的第 1 天和第 5-9 天进行。在 PIRRT 治疗前 8 小时给予 600 万 IU（MIU）多黏菌素甲磺酸盐，然后每 8 小时给予 3MIU。该研究已在 clinicaltrails.gov（NCT02556190）注册。
PIRRT 清除了相当数量的多黏菌素和多黏菌素甲磺酸盐，多黏菌素的中位透析器血浆清除率为 70.1mL/min（IQR 36.6-96.2），多黏菌素甲磺酸盐为 69.3mL/min（IQR 56.3-318.7）。收集的总透析液中多黏菌素的中位数量为 154mg（IQR 105-175），相当于每日剂量的约 50%。多黏菌素的第 1 天累积峰浓度为 5.79mg/L（IQR 4.14-8.79），第 5-9 天为 9.49mg/L（IQR 8.39-10.41）。Cmax 与体重呈显著负相关。
PIRRT 消除了每日给予多黏菌素剂量的约一半。甚至给予 6MIU 的多黏菌素甲磺酸盐负荷剂量也不能确保所有重症患者立即获得足够的多黏菌素血浆水平。然而，我们测量到了显著的多黏菌素蓄积，这表明多黏菌素甲磺酸盐的剂量应根据体重和 RRT 强度进行调整。
