Risk factors for acute kidney injury in patients treated with polymyxin B or colistin methanesulfonate sodium

Int J Antimicrob Agents. 2014 Apr;43(4):349-52. doi: 10.1016/j.ijantimicag.2013.12.002. Epub 2013 Dec 15.

Abstract

Polymyxin B (PMB) and colistin, administered as the prodrug colistin methanesulfonate sodium (CMS), are increasingly used to treat carbapenem-resistant Gram-negative bacteria. Nephrotoxicity is the major dose-limiting adverse effect of both polymyxins. A retrospective cohort study of 132 patients was conducted to evaluate risk factors for acute kidney injury (AKI), classified according to Acute Kidney Injury Network criteria, in patients treated with ≥48h of intravenous PMB or CMS, with particular focus on potential differences between each polymyxin. The overall incidence of AKI was 25.8% (34/132) [20.8% (20/96) and 38.9% (14/36) in patients treated with PMB and CMS, respectively; P=0.06]. In the Cox regression model, doses ≥2million International Units (MIU) of PMB or >9MIU of CMS were the only variable independently associated with AKI [adjusted hazard ratio (aHR)=2.11, 95% confidence interval (CI) 1.01-4.41; P=0.04]. Vancomycin co-administration was strongly associated with AKI, although this was not statistically significant (aHR=2.22, 95% CI 0.98-5.04; P=0.058). There was no statistically significant difference in the incidence of AKI between patients treated with PMB or CMS in the multivariate model (aHR=1.74, 95% CI 0.82-3.69; P=0.15). High dose was the main risk factor for AKI regardless of the polymyxin administered. Vancomycin co-administration likely increases the risk of AKI. Although there was a higher overall incidence of AKI in patients treated with CMS compared with PMB, CMS was not significantly associated with this outcome after adjusting for the above variables.

Keywords: Acute Kidney Injury Network; Acute kidney injury; Acute renal failure; Cohort study; Colistin; Creatinine; Polymyxin.

MeSH terms

  • Acinetobacter Infections / drug therapy
  • Acinetobacter baumannii / drug effects
  • Acinetobacter baumannii / pathogenicity
  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / epidemiology*
  • Acute Kidney Injury / mortality
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use
  • Cohort Studies
  • Colistin / adverse effects
  • Colistin / analogs & derivatives*
  • Colistin / therapeutic use
  • Female
  • Hospital Mortality
  • Humans
  • Klebsiella Infections / drug therapy
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / pathogenicity
  • Male
  • Middle Aged
  • Polymyxin B / adverse effects*
  • Polymyxin B / therapeutic use
  • Pseudomonas Infections / drug therapy
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / pathogenicity
  • Retrospective Studies
  • Risk Factors
  • Vancomycin / adverse effects*
  • Vancomycin / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Vancomycin
  • colistinmethanesulfonic acid
  • Polymyxin B
  • Colistin