title: In vitro assessment and multicenter cohort study of comparative nephrotoxicity rates associated with colistimethate versus polymyxin B therapy.
abstract: Despite concerns of nephrotoxicity, polymyxin antibiotics often remain the only susceptible agents for multidrug-resistant (MDR) Gram-negative bacteria. Colistin has been more commonly used clinically due to a perceived safety benefit. We compared the nephrotoxicity of colistin to polymyxin B. The in vitro cytotoxicity of colistin was compared to polymyxin B in two mammalian renal cell lines. To validate the clinical relevance of the findings, we evaluated adult patients with normal renal function who received a minimum of 72 h of polymyxin therapy in a multicenter study. The primary outcome was the prevalence of nephrotoxicity, as defined by the RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria. Colistin exhibited an in vitro cytotoxicity profile similar to polymyxin B. A total of 225 patients (121 receiving colistimethate, 104 receiving polymyxin B) were evaluated. Independent risk factors for colistimethate-associated nephrotoxicity included age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.00 to 1.07; P = 0.03), duration of therapy (OR 1.08; 95% CI, 1.02 to 1.15; P = 0.02), and daily dose by ideal body weight (OR 1.40; 95% CI, 1.05 to 1.88; P = 0.02). In contrast, cystic fibrosis was found to be a protective factor in patients who received colistimethate (OR, 0.03; 95% CI, 0.001 to 0.79; P = 0.04). In a matched analysis based on the risk factors identified (n = 76), the prevalence of nephrotoxicity was higher with colistimethate than with polymyxin B (55.3% versus 21.1%; P = 0.004). Polymyxin B was not found to be more nephrotoxic than colistin and may be the preferred polymyxin for MDR infections. A prospective study comparing the two polymyxins directly is warranted.
authors.affiliation: Department of Pharmacy, St. Luke's Episcopal Hospital, Houston, Texas, USA.
authors.forename: Kady
authors.initials: K
authors.lastname: Phe
authors.forename: Yuman
authors.initials: Y
authors.lastname: Lee
authors.forename: Patrick M
authors.initials: PM
authors.lastname: McDaneld
authors.forename: Nishant
authors.initials: N
authors.lastname: Prasad
authors.forename: Taijun
authors.initials: T
authors.lastname: Yin
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Figueroa
authors.forename: William L
authors.initials: WL
authors.lastname: Musick
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Cottreau
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.forename: Vincent H
authors.initials: VH
authors.lastname: Tam
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003091:Colistin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008875:Middle Aged; D011113:Polymyxins / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D011113:Polymyxins; C004691:colistinmethanesulfonic acid; D003091:Colistin