title: High dose intravenous colistin methanesulfonate therapy is associated with high rates of nephrotoxicity; a prospective cohort study from Saudi Arabia.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  High 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.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, King Faisal Specialist Hospital and Research Centre, PO Box 3354, MBC 46, Riyadh, 11211, Saudi Arabia. asomrani@kfshrc.edu.sa.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Omrani
authors.affiliation: Department of Pharmacy, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. walfahad@psmmc.med.sa.
authors.forename: Wafa A
authors.initials: WA
authors.lastname: Alfahad
authors.affiliation: Department of Biostatistics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. shoukri@kfshrc.edu.sa.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Shoukri
authors.affiliation: Department of Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. albaadani.id@gmail.com.
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Baadani
authors.affiliation: Department of Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. sul111ksa@hotmail.com.
authors.forename: Sultan
authors.initials: S
authors.lastname: Aldalbahi
authors.affiliation: Department of Pharmacy, Prince Sultan Cardiac Centre, Riyadh, Saudi Arabia. AAlMitwazi@pscc.med.sa.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Almitwazi
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. draalbarrak@yahoo.com.
authors.forename: Ali M
authors.initials: AM
authors.lastname: Albarrak
mesh_terms: D058186:Acute Kidney Injury / Q000453:epidemiology / Q000209:etiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003091:Colistin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006801:Humans; D008297:Male; D008698:Mesylates / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D011247:Pregnancy; D011446:Prospective Studies; D012189:Retrospective Studies; D012529:Saudi Arabia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D008698:Mesylates; C045880:methanesulfonic acid; D003091:Colistin