Nephrotoxicity of Colistin: New Insight into an Old Antibiotic

We commend Hartzell et al. [1] for their study on the nephrotoxicity associated with intravenous administration of colis-timethate sodium (hereafter, referred to as " colistin "). Despite its retrospective nature , the study has special merit because it addresses an important clinical issue. Colistin (also known as polymyxin E) was developed ∼60 years ago but was rarely used in clinical practice (except for patients with cystic fibrosis) during the period 1980–2000 because of concerns related to reported high rates of nephrotox-icity. However, it was recently reintroduced in clinical practice in many parts of the world, primarily as a consequence of necessity. Specifically, it was revived because of the challenges faced by physicians caring for patients with infections due to lactose-nonfermenting, gram-negative ba-cilli, mainly Pseudomonas aeruginosa and Acinetobacter baumannii [2]. There is certainly a disparity in the reported rates of nephrotoxicity associated with intravenous administration of colis-tin between old and recent studies. Indeed, in a systematic review of the relevant literature , the reported rate of nephrotox-icity was higher in older studies than in studies published after 1995 [3]. This may be partly caused by the lack of common criteria to define renal function impairment. However, the variance in definitions alone cannot account for the important differences in reported nephrotoxicity associated with colistin. Fewer chemical impurities of colistin, better intensive care unit monitoring (especially of the patient's hydration status), and avoidance of coad-ministration of other nephrotoxic drugs may be the main causes of the differences [3]. A growing body of evidence from studies originating from hospitals in several countries has shown that colistin is effective and acceptably safe [4]. Although most of the revival of polymyxin use is associated with colistin, satisfactory figures of effectiveness and safety have also been reported for the other polymyxin antibiotic available for intravenous use, poly-myxin B [5]. The assessment of nephrotoxicity associated with a medication is not an easy task. Ideally, a control group receiving another antibiotic or placebo is needed for better insight in studies that address issues of adverse events. We believe that the lack of randomized, controlled trials of intravenous colistin hampers the evaluation of its effectiveness and safety. However, the fact that intravenous colistin is administered mainly to patients with infection due to polymyxin-only-susceptible bacteria makes the performance of relevant ran-domized, controlled trials unlikely at this time. This is because it may be unethical not to prescribe colistin for a patient …