Colistin: An Update on the Antibiotic of the 21st Century

Silpak Biswas; Jean-Michel Brunel; Jean-Christophe Dubus; Martine Reynaud-Gaubert; Jean-Marc Rolain


Expert Rev Anti Infect Ther. 2012;10(8):917-934. 

In This Article

Toxicity & Adverse Effects

Nephrotoxicity and neurotoxicity are the most common adverse effects of polymyxins.[139–142] Toxicity is dose dependent and reversible on discontinuation of treatment. The exact molecular mechanism of toxicity is, however, not known. Polymyxins were associated with high rates of nephrotoxicity.[10] Total cumulative CMS dose is associated with kidney damage, suggesting that shortening of treatment duration could decrease the incidence of nephrotoxicity. Previous studies showed that CMS nephrotoxicity compared favorably with that of the aminoglycosides, which were originally believed to be less toxic when they were used to replace colistin 30 years ago.[143,144] Another study showed that as many as 20% of patients experienced a decline in renal function after polymyxin therapy.[140] The use of polymyxins was abandoned in the early 1970s because of initial reports on patients with abnormal renal function due to nephrotoxic side effects.[140,142,145] Using a variety of definitions for nephrotoxicity, approximately 10–37% of patients receiving CMS with doses of 5–12 mg/kg/day experience an increase in serum creatinine level.[146–150] The nephrotoxicity was found in 10% of patients with MDR bacterial infections in the largest study performed to date by Falagas et al. after intravenous colistin therapy.[124]

The recent retrospective cohort study by Kwon et al. identified predictors of acute kidney injury (AKI) associated with intravenous CMS treatment.[151] A total of 71 adult patients receiving CMS ≥72 h were studied. AKI was defined using Risk, Injury, Failure, Loss and End-stage kidney disease criteria according to serum creatinine. The median total dose of CMS was 54.3 mg/kg. In this study, AKI developed in 53.5% of patients. AKI is associated with high mortality and treatment with renal replacement therapy is expensive. Hartzell et al. recently reported that the incidence of nephrotoxicity using CMS was 45% using Risk, Injury, Failure, Loss and End-stage kidney disease criteria for defining AKI.[152] Ko et al. recently reported AKI in 54.6% of 119 patients who had received intravenous CMS for over 72 h.[153] In another study, Deryke et al. reported nephrotoxicity in a teaching hospital in the USA.[154] In this study, 30 patients were prescribed CMS for the treatment of MDR P. aeruginosa and K. pneumoniae isolated primarily from respiratory (63%) or urine (20%) sources. Excessive daily dosing led to the more frequent development of nephrotoxicity in this study. As such, close monitoring of renal function, specifically during the first 5 days of therapy, is important for clinicians.

Neurotoxicity does not seem to be a major issue during colistin treatment. The incidence of neurotoxicity in earlier studies of colistin was approximately 7%.[146,155] Dizziness, weakness, visual disturbance and neuromuscular blockade leading to respiratory failure have been reported in rare cases.[2]