Single- And Multiple-Dose Pharmacokinetics and Total Removal of Colistin in Critically Ill Patients With Acute Kidney Injury Undergoing Prolonged Intermittent Renal Replacement Therapy

Julius J Schmidt, Ann-Kathrin Strunk, Sascha David, Stefanie M Bode-Böger, Jens Martens-Lobenhoffer, Wolfgang Knitsch, Stephan Scherneck, Tobias Welte, Jan T Kielstein

J Antimicrob Chemother. 2019 Apr 1;74(4):997-1002.

PMID: 30624668

Abstract:

Background:




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.













Objectives:




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.













Methods:




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).













Results:




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.













Conclusions:




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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP296250549	BMS-341400 methanesulfonate		296250-54-9	Price