title: Nephrotoxicity of Polymyxins: Is There Any Difference between Colistimethate and Polymyxin B?
abstract: Nephrotoxicity is a common adverse effect of the clinically used polymyxins, colistin and polymyxin B. This adverse effect is dose limiting for both polymyxins, as the plasma polymyxin concentrations associated with renal damage overlap those required for antibacterial effect. Since development of acute kidney injury (AKI) during therapy is highly undesirable, it is extremely important to know whether there is any difference between the nephrotoxic potential of colistin (administered as its inefficient prodrug, colistimethate) and polymyxin B (administered as the active form). Both polymyxins are cytotoxic to renal tubular cells and are prone to cause nephrotoxicityin vivobecause of the renal handling mechanisms that facilitate accumulation of these compounds in these cells, processes that are reviewed in this article. Also reviewed are the emerging data that strongly suggest significantly higher rates of AKI in patients treated with colistimethate compared to patients treated with polymyxin B. This finding may be due to differences in pharmacokinetics and renal handling mechanisms of colistimethate and formed colistin versus polymyxin B, and consequently the relative amount of polymyxin material delivered to tubular cells. A lower risk of AKI with polymyxin B is one of several potential advantages over colistimethate. The relative safety and efficacy of the two agents require closer examination in well-designed clinical studies.
authors.affiliation: Infectious Diseases Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.|Department of Internal Medicine, Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Zavascki
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia roger.nation@monash.edu.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Nation
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D001692:Biological Transport; D002986:Clinical Trials as Topic; D003091:Colistin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D011112:Polymyxin B / Q000009:adverse effects* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000009:adverse effects* / Q000493:pharmacokinetics; D051381:Rats; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D011355:Prodrugs; C004691:colistinmethanesulfonic acid; D011112:Polymyxin B; D003091:Colistin
keywords: acute kidney injury; colistimethate; colistin; polymyxin B; toxicodynamics