Evaluation of nephrotoxicity associated with intravenous colistin or polymyxin B

Introduction:

Although structurally very similar, the polymyxins are not clinically interchangeable. Colistin is administered as an inactive prodrug, and recent studies have demonstrated that less than 20­-25% of the dose will be converted to active drug outside of the urinary tract. Weight-based polymyxin B dosing, however, produces a predictable relationship between dose and serum levels. As a result, utilization of high-dose polymyxin B replaced colistin for infections outside of the urinary tract.

Objectives:

The purpose of this study was to evaluate whether there has been a change in associated nephrotoxicity rates since adopting aggressive polymyxin B dosing instead of traditional, weight-based colistin for treatment of infections by multidrug-resistant organisms (MDROs).

Study Design:

This was a retrospective, single­-center cohort study.

Methods:

Forty-four adult patients who received intravenous colistin or polymyxin B from 2010 through 2015 were identified for inclusion in the study. Baseline demographic data were collected and the presence of other risk factors for nephrotoxicity (i.e. concomitant nephrotoxins, Modified Acute Physiology Score, hypertension, and diabetes) were assessed. Nephrotoxicity was defined as meeting RIFLE Criteria for acute kidney injury or failure. Polymyxin regimens and renal function were tracked throughout the treatment course.

Results:

Twenty-one patients received intravenous colistin and 23 received intravenous polymyxin B during the 5-year study period. There were no significant differences in study patients at baseline, including risk factors for nephrotoxicity. The majority of infections were caused by Pseudomonas spp. (39%) with the respiratory tract (57%) most commonly identified as the infection source. There were no statistically significant differences between the polymyxin B and colistin groups in the rates of nephrotoxicity (29.4% vs. 35.0%), neurotoxicity (13.0% vs. 9.5%), or mortality (34.8% vs. 38.1%) observed in this study.

Conclusions:

Aggressive, weight-based polymyxin B dosing for MDRO infections will continue to be utilized as no differences in nephrotoxicity or neurotoxicity were demonstrated.