Development of Acute Kidney Injury in Patients treated with Polymyxin B Compared to Colistimethate Sodium

Background: Polymyxin use is associated with increasing nephrotoxicity, with recent studies suggesting greater toxicity with colistimethate (CMS) compared to polymyxin B (PB). However, this difference is not well established with conflicting results in some studies. The objective of this study was to determine the acute kidney injury (AKI) incidence in patients treated with polymyxin antimicrobials.

Methods: This retrospective evaluation included adults treated with intravenous PB or CMS for at least 48 hours between 07/01/2006 and 09/30/2015. Patients with cystic fibrosis or those receiving renal replacement therapy were excluded. Data were obtained from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust. Data collected included demographics, length of stay, comorbidities, Charlson Comorbidity Index, laboratory values, concomitant anti-infectives, and nephrotoxins. Basic descriptive statistics and multivariable logistic regression were performed to identify risk factors for AKI, as defined by RIFLE criteria.

Results: A total of 230 patients were evaluated, 59 treated with PB and 171 with CMS. The PB cohort was older (56.4±12.6 v 51.0±15.5 years, p=0.01) and had a greater proportion of Caucasian patients (98.3% v 87.1%, p=0.03) but no difference in duration of the therapy. Acute kidney injury occurred in 31/55 (52.5%) patients treated with PB and 99/171 (57.9%) of patients treated with CMS (p=0.57). There were no differences in AKI at any RIFLE stage with PB compared to CMS: Risk (27.1% v 24.6%, p=0.78), Injury (17.0% v 27.5%, p=0.17), or Failure (8.5% v 7.0%, p=0.82). Independent predictors of AKI in this patient population by multivariate logistic regression were high polymyxin dose [PB ≥ 200 mg/d, CMS ≥ 270 mg/d colistin base activity] (OR 3.05, 95% CI 1.57-6.15), duration of therapy, (OR 2.82, 95% CI 1.55 – 5.21), concurrent aminoglycosides (OR 1.94, 95% CI 1.04-3.69), and concurrent loop diuretics (OR 2.10, 95% CI 1.16-3.83).

Conclusion: There was no difference in the incidence of AKI in patients treated with PB and CMS. Independent risk factors for nephrotoxicity in polymyxin-treated patients were high polymyxin dose, duration of therapy, aminoglycoside use, and loop diuretic use.