Trough colistin plasma level is an independent risk factor for nephrotoxicity: a prospective observational cohort study

Abstract

BackgroundData regarding the most efficacious and least toxic schedules for the use of colistin are scarce. The aim of this study was to determine the incidence and the potential risk factors of colistin-associated nephrotoxicity including colistin plasma levels.MethodsA prospective observational cohort study was conducted for over one year in patients receiving intravenous colistin methanesulfonate sodium (CMS). Blood samples for colistin plasma levels were collected immediately before (Cmin) and 30 minutes after CMS infusion (Cmax). Renal function was assessed at baseline, on day 7 and at the end of treatment (EOT). Severity of acute kidney injury (AKI) was defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria.ResultsOne hundred and two patients met the inclusion criteria. AKI related to CMS treatment on day 7 and at the end of treatment (EOT) was observed in 26 (25.5%) and 50 (49.0%) patients, respectively. At day 7, Cmin (OR, 4.63 [2.33-9.20]; P < 0.001) was the only independent predictor of AKI. At EOT, the Charlson score (OR 1.26 [1.01-1.57]; P = 0.036), Cmin (OR 2.14 [1.33-3.42]; P = 0.002), and concomitant treatment with ≥ 2 nephrotoxic drugs (OR 2.61 [1.0-6.8]; P = 0.049) were independent risk factors for AKI. When Cmin was evaluated as a categorical variable, the breakpoints that better predicted AKI were 3.33 mg/L (P < 0.001) on day 7 and 2.42 mg/L (P < 0.001) at EOT.ConclusionsWhen using the RIFLE criteria, colistin-related nephrotoxicity is observed in a high percentage of patients. Cmin levels are predictive of AKI. Patients who receive intravenous colistin should be closely monitored and Cmin might be a new useful tool to predict AKI.

Risk factors for colistin-associated nephrotoxicity and mortality in critically ill patients

“…Some recent studies have investigated the risk factors for colistin-associated NT (8,21,(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Results from previous studies are given with their significance levels in Table 5.…”

“…Two large studies demonstrated that patients with septic shock had a higher incidence of NT (26)(27)(28)(29).…”

Risk Factors for Colistin-Associated Acute Kidney Injury: A Multicenter Study from Turkey

“…The rates of colistin-induced AKI reported in the literature vary between 11z and 53.5z (3,4,6,9,10,(13)(14)(15)(16)(17). This variability could be attributed to the dose and duration of the therapies, and to the varying definitions of AKI.…”

“…The mechanism of renal toxicity is not exactly clear, but proximal tubulopathy and mammalian uroepithelium toxicity were observed in some studies. It has been reported that the nephrotoxicity of colistin is generally mild and reversible (2)(3)(4)(5)(6).…”

Successful Colistin Treatment of Multidrug-Resistant <i>Pseudomonas aeruginosa</i> Infection Using a Rapid Method for Determination of Colistin in Plasma: Usefulness of Therapeutic Drug Monitoring

“…A prospective observational cohort study demonstrated that trough plasma levels of colistin is an independent risk factor for nephrotoxicity 13) and that trough plasma colistin levels of 3.33 mg/L on day 7 best predicted acute kidney injury (AKI). Information on the plasma levels of colistin will be helpful for future dosing recommendations.…”