title: Continuous renal replacement therapy-related strategies to avoid colistin toxicity: a clinically orientated review.
abstract: Polymyxins are 'old' antimicrobials which were abandoned for almost 30 years because of significant renal and neurological toxicity. However, the alarming rise in multiresistant Gram-negative bacterial infections worldwide has revived interest in these 'forgotten' agents. Colistin (polymyxin E) is one of the main antibiotics of this class. It is most often administered as the prodrug colistimethate sodium. Doses for treatment of systemic infections in adults range between 3 and 9 million IU per day. Colistin is increasingly used to treat pneumonia and bacteremia in critically ill patients. During their intensive care unit stay, many of these patients will need continuous renal replacement therapy (CRRT) because of acute kidney injury or an unstable hemodynamic condition. Based on recent pharmacological data and our own experience, we postulate that patients undergoing CRRT may receive substantially higher doses of colistin (i.e. a high loading dose, followed by a maintenance dose of up to 4.5 million IU t.i.d.). Treatment can be continued for a prolonged time period without increasing toxicity. CRRT counteracts colistin accumulation because the drug is continuously filtered and also significantly adsorbed in the bulk of the dialysis membrane. Implementing such a 'CRRT rescue' therapy does require the strict use of highly adsorptive dialysis membranes in association with citrate anticoagulation to increase membrane performance.
authors.affiliation: Department of Intensive Care Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Honoré
authors.forename: Rita
authors.initials: R
authors.lastname: Jacobs
authors.forename: Olivier
authors.initials: O
authors.lastname: Joannes-Boyau
authors.forename: Stijn
authors.initials: S
authors.lastname: Lochy
authors.forename: Willem
authors.initials: W
authors.lastname: Boer
authors.forename: Elisabeth
authors.initials: E
authors.lastname: De Waele
authors.forename: Viola
authors.initials: V
authors.lastname: Van Gorp
authors.forename: Jouke
authors.initials: J
authors.lastname: De Regt
authors.forename: Vincent
authors.initials: V
authors.lastname: Collin
authors.forename: Herbert D
authors.initials: HD
authors.lastname: Spapen
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003091:Colistin / Q000009:adverse effects* / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D017582:Renal Replacement Therapy / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin