Nephrotoxicity of polymyxins

is there any difference between colistimethate and polymyxin B?

Alexandre P Zavascki, Roger L Nation

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

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 nephrotoxicity in vivo because 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.

Original languageEnglish
Article numbere02319-16
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number3
DOIs
Publication statusPublished - 1 Mar 2017

Keywords

  • Acute kidney injury
  • Colistimethate
  • Colistin
  • Polymyxin B
  • Toxicodynamics

Cite this

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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 nephrotoxicity in vivo because 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.",
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Nephrotoxicity of polymyxins : is there any difference between colistimethate and polymyxin B? / Zavascki, Alexandre P; Nation, Roger L.

In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 3, e02319-16, 01.03.2017.

Research output: Contribution to journalArticleResearchpeer-review

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