Colistin Pharmacokinetics in Critically Ill Patients During Extended Dialysis

Study Overview
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Brief Summary
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The emergence of multidrug-resistant bacteria has recently renewed interest in colistin. Data on dosing in critically ill patients undergoing extended dialysis are missing. The aim of this study is to determine the pharmacokinetics of colistin during extended dialysis in critically ill patients and to provide dosing guidelines for this drug.

Detailed Description
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Due to the lack of new antibiotics for the treatment of critically ill patients with multidrug-resistant bacteria, interest in old antibiotics like colistin re-emerged. Lastly, colistin is administered more frequently especially in cases of infections due to Pseudomonas aeruginosa, Klebsiella pneumoniae or Acinetobacter baumanii in intensive care units (ICUs) around the world. However, dosing of colistin in critically ill patients undergoing renal replacement therapy is based on scarce data. The aim of this study is to evaluate single and multiple-dose pharmacokinetics of both colistin and its inactive prodrug colistin-methanesulfonate (CMS) in critically ill patients with acute kidney injury (AKI) undergoing extended daily dialysis (EDD). The investigators perform a prospective clinical pharmacokinetic single- and multiple-dose study in the medical and surgical ICUs of the Hannover Medical School. ICU patients with anuric AKI being treated with EDD and receiving i.v. colistin are studied on day 1 and (if possible) on day 5-9 of treatment. A loading dose of 6 Mio IU colistin ís administered 8 hours prior to the EDD session followed by 3 Mio IU every 8 hours. Colistin Plasma concentration levels as well as dialyzer clearance rates are measured at different time points.

Official Title
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Colistin Pharmacokinetics in Critically Ill Patients With Acute Kidney Injury AKIN III During Extended Dialysis Using the GENIUS Dialysis System

Conditions
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Infection Due to Resistant Bacteria, Acute Kidney Injury

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Indication for colistin therapy Acute kidney injury AKIN III with need for renal replacement therapy Exclusion Criteria: participation in other studies pregnancy known colistin allergy or other contraindications for colistin therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Colistin elimination during extended dialysis | Colistin elimination during extended dialysis is measured on day 1 and day 9 after colistin therapy was started. Colistin elimination is measured by the total eliminated drug amount in the total spent dialysate | Participants will be followed for 10 days. Colistin elimination measured by the total drug amount in the collected spent dialysate | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Colistin peak concentration during extended daily dialysis C(max) |  | Participants will be followed for 10 days. Colistin concentration is measured at different time points after drug infusion: 0, 0.5, 1, 1.5, 2, 4, 6, 8) on day 1 and day 9 after therapy initiation | 
| Colistin trough Level during extended daily dialysis C(max) |  | Participants will be followed for 10 days. Colistin concentration is measured at different time points after drug infusion: 0, 0.5, 1, 1.5, 2, 4, 6, 8) on day 1 and day 9 after therapy initiation | 
| Colistin dialyzer clearance during extended dialysis |  | Participants will be followed for 10 days. Dialyzer clearance is calculated after 30 and 180 minutes of extended dialysis on day 1 and day 9 after therapy initiation |