title: Colistin: understanding and applying recent pharmacokinetic advances.
abstract: Colistin, the most widely used polymyxin antibiotic, was originally introduced in the late 1950s before the establishment of the present-day drug approval process. Originally shelved due to toxicity concerns, colistin, in the form of its inactive prodrug colistin methanesulfonate, has undergone a renaissance in the past 15 years. Unfortunately, this is not because of an improved adverse-effect profile but because colistin is among the only remaining antibiotics with activity against multidrug-resistant gram-negative bacilli. Pharmacokinetic and pharmacodynamic data are limited to guide the appropriate use of colistin; however, important advances have occurred over the past 5 years. Since its reintroduction, published reports regarding colistin have produced discordant results in terms of both efficacy and safety. Because the efficacy and toxicity of colistin are dose dependent, the impact of discordant dosing recommendations cannot be understated. This review highlights the issues leading to differing and often conflicting dosing recommendations, reviews the recent pharmacokinetic advances, and provides recommendations for the optimal use of colistin.
authors.affiliation: Department of Pharmacy Services, Parkland Health and Hospital System, Dallas, Texas.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Ortwine
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kaye
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Jason M
authors.initials: JM
authors.lastname: Pogue
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003091:Colistin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin
keywords: colistimethate; colistin; pharmacodynamics; pharmacokinetics; polymyxins