• Jason M Pogue, Jiha Lee, Dror Marchaim, Victoria Yee, Jing J Zhao, Teena Chopra, Paul Lephart, and Keith S Kaye.
• Department of Pharmacy Services, Sinai-Grace Hospital, Detroit Medical Center, Michigan, USA. jpogue@dmc.org
• Clin. Infect. Dis. 2011 Nov 1;53(9):879-84.

BackgroundColistin, originally abandoned due to high rates of nephrotoxicity, has been recently reintroduced due to activity against carbapenem-resistant Gram-negative organisms. Recent literature, largely obtained from outside the United States, suggests a lower rate of nephrotoxicity than historically reported.MethodsA retrospective cohort of all patients who received colistin for ≥ 48 hours at the Detroit Medical Center over a 5-year period was performed to determine the rate of colistin-associated nephrotoxicity as defined by the RIFLE criteria.ResultsFifty-four (43%) patients in the cohort developed nephrotoxicity. Patients who experienced nephrotoxicity after colistin administration were in the Risk (13%), Injury (17%), or Failure (13%) categories per RIFLE criteria. Patients who developed nephrotoxicity received significantly higher mean doses than those who did not (5.48 mg/kg per day vs 3.95 mg/kg per day; P < .001), and the toxicity occurred in a dose-dependent fashion. Independent predictors for nephrotoxicity were a colistin dose of ≥ 5.0 mg/kg per day of ideal body weight (odds ratio [OR], 23.41; 95% confidence interval [CI], 5.3-103.55), receipt of concomitant rifampin (OR, 3.81; 95% CI, 1.42-10.2), and coadministration of ≥ 3 concomitant nephrotoxins (OR, 6.80; 95% CI, 1.42-32.49).ConclusionsIn this retrospective cohort, nephrotoxicity (as defined by RIFLE criteria) occurred among 43% of treated patients in a dose-dependent manner. Higher colistin doses, similar to those commonly used in the United States, led to a relatively high rate of nephrotoxicity. These data raise important questions regarding the safe use of colistin in the treatment of multidrug-resistant pathogens.

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