Incidence of and Risk Factors for Colistin-Associated Nephrotoxicity in a Large Academic Health System

• Published in: Clinical infectious diseases Vol. 53; no. 9; pp. 879 - 884
• Main Authors: Pogue, Jason M., Lee, Jiha, Marchaim, Dror, Yee, Victoria, Zhao, Jing J., Chopra, Teena, Lephart, Paul, Kaye, Keith S.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-11-2011
• Subjects: Academic Medical Centers; Adult; Aged; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; ARTICLES AND COMMENTARIES; Bacteria; Biological and medical sciences; Body weight; Cohort Studies; Colistin - administration & dosage; Colistin - adverse effects; Dosage; Drug dosages; Drug resistance; Female; Gram-negative bacteria; Humans; Incidence; Infections; Infectious diseases; Intensive care units; Kidney Diseases - chemically induced; Kidney Diseases - epidemiology; Male; Medical sciences; Middle Aged; Nephrotoxicity; Pathogens; Pharmacology. Drug treatments; Predisposing factors; Renal insufficiency; Retrospective Studies; Rifles; Risk Factors; Sepsis; Toxicity; United States - epidemiology; United States; United States > US; USA; USA, Michigan, Detroit; Infection; Health system; Antibiotic; Colistin; Cyclic peptides; Polypeptide; Toxicity; Risk factor; Antibacterial agent; Epidemiology; Incidence
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/cir611

Background. Colistin, 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. Methods. A 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. Results. Fifty-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). Conclusions. In 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.