Julius J Schmidt1, Ann-Kathrin Strunk1, Sascha David1, Stefanie M Bode-Böger2, Jens Martens-Lobenhoffer2, Wolfgang Knitsch3, Stephan Scherneck4, Tobias Welte5, Jan T Kielstein1,6. 1. Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany. 2. Institute of Clinical Pharmacology, Otto von-Guericke-University of Magdeburg, Magdeburg, Germany. 3. Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany. 4. Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technical University of Braunschweig, Braunschweig, Germany. 5. Department of Pulmonary Medicine, Hannover Medical School, Hannover, Germany. 6. Medical Clinic V | Nephrology | Rheumatology | Blood Purification, Academic Teaching Hospital Braunschweig, Braunschweig, Germany.
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.
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 illpatients. However, we measured significant colistin accumulation, suggesting that the dose of colistin methanesulfonate should be adjusted according to body weight and RRT intensity.
Authors: Stefan Felix Ehrentraut; Stefan Muenster; Stefan Kreyer; Nils Ulrich Theuerkauf; Christian Bode; Folkert Steinhagen; Heidi Ehrentraut; Jens-Christian Schewe; Matthias Weber; Christian Putensen; Thomas Muders Journal: Microorganisms Date: 2020-03-15