Comparative Nephrotoxicity of Polymyxin B and Colistimethate Sodium in Patients with Cystic Fibrosis

Background: Nephrotoxicity is the most prominent dose-limiting adverse effect of the polymyxins; however, the relative toxicity of the two systemic agents, polymyxin B (PB) and colistimethate sodium (CMS), in patients with cystic fibrosis (CF) is not known. We evaluated the incidence of acute kidney injury (AKI) in adult CF patients treated with PB compared to CMS.

Methods: All adult CF inpatients from July 2006 – September 2015 treated with intravenous PB or CMS for at least 48 hrs were evaluated. Patients receiving renal replacement therapy were excluded. All of the following data were obtained from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust: demographics, length of stay, comorbidities, Charlson Comorbidity Index, laboratory values, concomitant anti-infectives, and nephrotoxins. AKI was defined by the RIFLE criteria. Basic descriptive statistics and multivariable logistic regression analysis were performed to identify risk factors for AKI.

Results: A total of 220 patients met criteria for inclusion, 29 treated with PB and 191 with CMS. At baseline, PB-treated patients had higher actual body weight (57.4±11.6 v 51.8±10.5 kg, p=0.02) and higher median baseline serum creatinine [0.8 (0.6-0.9) v 0.7 (0.6-0.8) mg/dL, p=0.01). Acute kidney injury occurred in 10/29 (34.5%) and 57/191(29.8%) of patients treated with PB and CMS, respectively (p=0.77). There were no differences between PB and CMS at any RIFLE stage: Risk (20.7% v 25.1%, p=0.77), Injury (13.8% v 4.7%, p=0.13), or Failure (0% v 0%). Peak serum creatinine was higher with PB than CMS (1.2 v 0.8 mg/dL, p=0.006). Duration of therapy (OR 2.11, 95% CI 1.11-4.11), concurrent aminoglycoside use (OR 2.20, 95% CI 1.06-4.59), and concurrent loop diuretic use (OR 3.22, 95% CI 1.28-8.32) were independent risk factors for the development of AKI in multivariate logistic regression analysis.

Conclusion: There was no difference in the incidence of AKI in CF patients treated with PB compared to CMS. Independent risk factors for the development of AKI in this population were duration of therapy, aminoglycoside use, and loop diuretic use.