485Colistin Nephrotoxicity in Critically Ill Patients after Implementation of a New Dosing Strategy

Background. Intravenous colistin is increasingly used to treat multidrug-resistant Gram-negative infections. Highly variable nephrotoxicity rates were reported by recent studies. Recent PK/PD studies propose a loading dose and a maintenance dose equation for better efficacy; and data are scarce for renal toxicity of such regimens. This study aimed to evaluate incidence and risk factors for nephrotoxicity associated with colistin after implementation of a new dosing regimen including a loading dose. Methods. A prospective observational study was conducted among adult patients who received at least 48 hours of intravenous colistin from December 1, 2012 to January 1, 2014 at medical and surgical intensive care unit (ICU)s in a university hospital. Severity of acute kidney injury (AKI) was defined by RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria. Results. Fifty-nine patients met the inclusion criteria, and 31 (52.5%) developed nephrotoxicity. The APACHE-II score at colistin initiation was > 15 in 81% of patients. The median time to nephrotoxicity was 7 days (range, 3 to 18). Patients with AKI were in Risk (10.2%), Injury (16.9%), Failure (25.4%) and no patients had long-term kidney failure or required hemodialysis after their course of colistin therapy. A logistic regression model identified three predictors of colistin-associated nephrotoxicity; age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.08), the number of days that estimated target plasma concentrations of colistin were≥ 3.5 mg/L in the first week of therapy (OR, 2.4; 95% CI, 1.25 to 4.47), and baseline creatinine (OR, 0.2; 95% CI, 0.07 to 0.60). Colistin nephrotoxicity was not related to the duration of therapy, total cumulative or average daily dose. Thirty-day all-cause mortality rates were similar among patients who developed nephrotoxicity and those who did not (58.1% vs 46.4 %, respectively; p = 0.53). Conclusion. In this cohort of severely ill ICU patients, colistin led to a relatively high rate of nephrotoxicity (52.5%). Further studies are needed to identify the optimal dose for both efficacy and safety. Monitoring colistin plasma concentrations may be a useful strategy for prevention of AKI. Disclosures. All authors: No reported disclosures.