title: Are there any ways around the exposure-limiting nephrotoxicity of the polymyxins?
abstract: The polymyxins (colistin and polymyxin B) have emerged over the past 20 years as essential antibacterial agents that often are the only remaining active class against troublesome multidrug-resistant Gram-negative bacilli such as carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae. The utility of this class is limited by its dose-dependent nephrotoxicity, which can occur in more than one-half of patients receiving therapy with either agent. Strategies are urgently needed to optimise the use of this class of agents to ensure optimal activity while minimising the treatment-limiting nephrotoxicity. This review will focus on risk factors for polymyxin-associated nephrotoxicity, potential strategies for limiting this exposure-dependent toxicity and, finally, unknowns and future research directions pertinent to this topic.
authors.affiliation: Department of Pharmacy Services, Detroit Medical Center, Sinai-Grace Hospital, Detroit, MI, USA; Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: jpogue@dmc.org.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Pogue
authors.affiliation: Department of Pharmacy Services, Parkland Health & Hospital System, Dallas, TX, USA; University of Texas Southwestern Medical School, Dallas, TX, USA.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Ortwine
authors.affiliation: Wayne State University School of Medicine, Detroit, MI, USA; Department of Internal Medicine, Detroit Medical Center, Detroit, MI, USA.
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kaye
mesh_terms: D058186:Acute Kidney Injury; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D011113:Polymyxins / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors; D012308:Risk Management
chemical_list: D000900:Anti-Bacterial Agents; D011113:Polymyxins
keywords: Acute kidney injury; Colistin; Multidrug-resistant; Nephrotoxicity; Polymyxin B