title: Predicting the risk of nephrotoxicity in patients receiving colistimethate sodium: a multicentre, retrospective, cohort study.
abstract: With increasing rates of infections caused by MDR Gram-negative organisms, clinicians resort to older agents such as colistimethate sodium (CMS) despite a significant risk of nephrotoxicity. Several risk factors for CMS-associated nephrotoxicity have been reported, but they have yet to be validated. We compared the performance of published mathematical models in predicting the risk of CMS-associated nephrotoxicity.
  
  
  
  In a multicentre, retrospective, cohort study, adult patients (≥18 years of age) were evaluated from five large academic medical centres in the USA. Patients with normal renal function (baseline serum creatinine ≤1.5 mg/dL) who received intravenous CMS for ≥72 h were followed for up to 30 days. The development of nephrotoxicity was as defined by the RIFLE criteria. Each published model was conditioned using patient-specific variables to predict the risk of nephrotoxicity. The predictive performance of the models was evaluated using the observed-to-expected (O/E) ratio. The most significant cut-off threshold for stratifying patients into high and low risk of nephrotoxicity was identified using classification and regression tree analysis.
  
  
  
  A total of 106 patients were examined (mean age 53.3 ± 14.9 years, 66% male); the overall observed nephrotoxicity rate was 52.8%. We identified a simple model demonstrating reasonable overall nephrotoxicity risk assessment [O/E ratio of 1.07 (95% CI = 0.81-1.39)] and high sensitivity (92.9%) in predicting nephrotoxicity development in patients on CMS therapy.
  
  
  
  We identified a model that could be incorporated into patient management strategies to reduce the risk of nephrotoxicity in patients requiring CMS therapy.
authors.affiliation: Department of Pharmacy, Baylor St Luke's Medical Center, Houston, TX, USA.
authors.forename: Kady
authors.initials: K
authors.lastname: Phe
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Shields
authors.affiliation: Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Tverdek
authors.affiliation: Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Aitken
authors.affiliation: Department of Pharmacy, Memorial Hermann-Texas Medical Center, Houston, TX, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Guervil
authors.affiliation: Department of Pharmacy, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Wai-Ying M
authors.initials: WM
authors.lastname: Lam
authors.affiliation: Department of Pharmacy, Harris Health System, Houston, TX, USA.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Musgrove
authors.affiliation: Department of Pharmacy, Texas A&M Health Science Center, Houston, TX, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Luce
authors.affiliation: Department of Pharmacy, Baylor St Luke's Medical Center, Houston, TX, USA vtam@uh.edu.|Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX, USA.
authors.forename: Vincent H
authors.initials: VH
authors.lastname: Tam
mesh_terms: D000046:Academic Medical Centers; D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology*; D061605:Administration, Intravenous; D000293:Adolescent; 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 / Q000031:analogs & derivatives*; D003661:Decision Support Techniques; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D012189:Retrospective Studies; D018570:Risk Assessment; D014481:United States; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; C004691:colistinmethanesulfonic acid; D003091:Colistin