title: Association between colistin dose and microbiologic outcomes in patients with multidrug-resistant gram-negative bacteremia.
abstract: BACKGROUND
  Colistin is increasingly used for the treatment of multidrug-resistant gram-negative infections. However, colistin dosing varies greatly and the optimal regimen is unknown. The purpose of this study was to determine if colistin dosing correlates with patient outcomes.
  
  
  METHODS
  This retrospective study included patients with gram-negative bacteremia treated with intravenous colistin for at least 72 hours. The primary objective was to determine if colistin dose (mg of colistin base activity/kg/day) independently predicts day-7 microbiological success. Secondary objectives included evaluation for an association between colistin dose and 7-day mortality, 28-day mortality, and the development of acute kidney insufficiency (AKI).
  
  
  RESULTS
  Seventy-six patients were included in the analysis, with 52 patients (68%) achieving 7-day microbiological success. The median colistin dose was significantly higher in patients who achieved microbiological success (2.9 vs 1.5 mg/kg/day; P = .011). After adjusting for baseline severity of illness and concomitant tigecyline use, higher colistin dose independently correlated with microbiological success (adjusted odds ratio per 1 mg/kg/day = 1.74; 95% confidence interval, 1.11-2.71; P = .015). The median colistin dose was also significantly higher among survivors at day 7 (2.7 vs 1.5 mg/kg/day; P = .007). However, no difference was observed in colistin dose when comparing survivors and nonsurvivors at day 28. A significantly higher colistin dose was given to patients who developed AKI during therapy (3.8 vs 1.6 mg/kg/day; P < .001).
  
  
  CONCLUSIONS
  Higher colistin dose independently predicted microbiological success, which may partially explain the similar association with 7-day mortality. However, higher colistin doses may also precipitate worsening renal function.
authors.affiliation: Department of Pharmacy, Community Hospital North, Indianapolis, IN, USA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Vicari
authors.forename: Seth R
authors.initials: SR
authors.lastname: Bauer
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Neuner
authors.forename: Simon W
authors.initials: SW
authors.lastname: Lam
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D003091:Colistin / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D005260:Female; D006090:Gram-Negative Bacteria / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin