High dose intravenous colistin methanesulfonate therapy is associated with high rates of nephrotoxicity; a prospective cohort study from Saudi Arabia

Ali M Albarrak,Ali A Almitwazi,Sultan Aldalbahi,Wafa A Alfahad,Abeer M Baadani,Ali S Omrani,Mohamed M Shoukri

doi:10.1186/s12941-015-0062-8

Abstract

BackgroundNephrotoxicity is an important adverse effect of colistin methanesulfonate (CMS) therapy. No data exist on rates and risk factors for colistin-related nephrotoxicity in Saudi Arabia (SA). We conducted a prospective cohort study to identify rates and risk factors for CMS nephrotoxicity in our patient population.MethodsWe prospectively included adult patients who received ≥48 hours of intravenous CMS therapy. Pregnant patients and those on renal replacement were excluded. Patients received 9 million units (mU) loading dose followed by 3 mU 8 hourly. In renal impairment, CMS dosing was adjusted according to calculated creatinine clearance (CrCl). Nephrotoxicity was defined as per RIFLE criteria (Risk, Injury, Failure, Loss and End-stage renal disease). Statistical analysis was performed using SPSS version 20.0 (IBM, Armonk, New York, USA). The study was approved by the institution’s Research Ethics Committee.ResultsA total of 67 patients were included in the study. Mean (±standard deviation) age was 57.5 (±24.0) years, Charlson Co-morbidity Score 2.88 (±2.39), CrCl 133.60 (±92.54) mL/min and serum albumin 28.65 (±4.45) g/L. Mean CMS dose was 0.11 (±0.04) mU/kg/day and mean total CMS dose received was 101.21 (±47.37) mU. Fifty-one (76.1%) patients developed RIFLE-defined nephrotoxicity. Mean total CMS dose and duration of therapy before onset of nephrotoxicity were 66.71 (±43.45) mU and 8.70 (±6.70) days, respectively. In bivariate analysis, patients with nephrotoxicity were significantly older (P 0.013) and had lower baseline serum albumin (P 0.008). Multivariate logistic regression identified serum albumin [odds ratio (OR) 0.72; 95% confidence interval (CI) 0.57–0.93; P 0.010] and intensive care admission (OR 16.38; 95% CI 1.37–195.55; P 0.027) as independent risk factors for CMS nephrotoxicity.ConclusionsHigh dose intravenous CMS therapy is associated with high rates of nephrotoxicity in SA. Independent risk factors for colistin nephrotoxicity were baseline hypoalbuminemia and intensive care admission.

Highlights

Nephrotoxicity is an important adverse effect of colistin methanesulfonate (CMS) therapy
In May 2012, we introduced a CMS dosing protocol utilizing loading doses with higher maintenance doses for all patients requiring intravenous CMS therapy
In multivariate logistic regression analysis, serum albumin [odds ratio (OR) 0.72; 95% confidence interval (CI) 0.57–0.93; P 0.010] and intensive care unit (ICU) status were the only independent risk factors for CMS-associated nephrotoxicity (Table 2)

Summary

Introduction

Nephrotoxicity is an important adverse effect of colistin methanesulfonate (CMS) therapy. No data exist on rates and risk factors for colistin-related nephrotoxicity in Saudi Arabia (SA). We conducted a prospective cohort study to identify rates and risk factors for CMS nephrotoxicity in our patient population. Many centres have changed their colistin dosing practice in an attempt to optimize antimicrobial treatment for patients with infections caused by carbapenem-resistant, Gramnegative bacteria [4]. A number of risk factors for CMS-associated nephrotoxicity have been identified in different studies. It appears that CMS-related nephrotoxicity is reversible in the majority of cases and does not usually result in premature treatment discontinuation [5].

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