title: Colistin Use in Patients With Reduced Kidney Function.
abstract: Colistin (polymyxin E) is a mainly concentration-dependent bactericidal antimicrobial active against multidrug-resistant Gram-negative bacteria. After being abandoned over the past 30 years due to its neuro- and nephrotoxicity, colistin has been reintroduced recently as a last-resort drug for the treatment of multidrug-resistant Gram-negative bacteria infections in combination with other antimicrobials. Unfortunately, although renal toxicity is a well-known dose-related adverse effect of colistin, relatively few studies are currently available on its peculiar pharmacodynamic/pharmacokinetic properties in clinical settings at high risk for drug accumulation, such as acute or chronic kidney disease. In these specific contexts, the risk for underdosing is also substantial because colistin can be easily removed by dialysis/hemofiltration, especially when the most efficient modalities of renal replacement therapy (RRT) are used in critically ill patients. For this reason, recent recommendations in patients undergoing RRT have shifted toward higher dosing regimens, and therapeutic drug monitoring is advised. This review aims to summarize the main issues related to chemical structure, pharmacodynamics/pharmacokinetics, and renal toxicity of colistin. Moreover, recent data and current recommendations concerning colistin dosing in patients with reduced kidney function, with special regard to those receiving RRT such as dialysis or hemofiltration, are also discussed.
authors.affiliation: Renal Failure Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy. Electronic address: enrico.fiaccadori@unipr.it.
authors.forename: Enrico
authors.initials: E
authors.lastname: Fiaccadori
authors.affiliation: Intermediate Care Unit, Emergency Department "Guglielmo da Saliceto" Hospital, Piacenza, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Antonucci
authors.affiliation: Hemodialysis Unit, Department of Nephrology and Urology, University of Rome "Sapienza," Rome, Italy.
authors.forename: Santo
authors.initials: S
authors.lastname: Morabito
authors.affiliation: Laboratory of Clinical Pharmacology and Pharmacogenetics, Infectious Disease Unit, Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: d'Avolio
authors.affiliation: Kidney-Pancreas Transplantation Unit, Parma University Hospital, Parma, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Maggiore
authors.affiliation: Renal Failure Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Regolisti
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology* / Q000628:therapy; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D003091:Colistin / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D016903:Drug Monitoring; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000139:chemically induced; D017410:Practice Guidelines as Topic; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology* / Q000628:therapy; D017582:Renal Replacement Therapy
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin
keywords: Acute kidney injury (AKI); chronic kidney disease (CKD); colistimethate; colistin; colistin methanesulfonate; colistin pharmacokinetics; continuous renal replacement therapies (CRRTs); critical illness; dialysis; hemofiltration; kidney function; nephrotoxicity; polymyxin E; renal toxicity; therapeutic drug monitors