Association between colistin dose and microbiologic outcomes in patients with multidrug-resistant gram-negative bacteremia

Clin Infect Dis. 2013 Feb;56(3):398-404. doi: 10.1093/cid/cis909. Epub 2012 Oct 22.

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.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Colistin / administration & dosage*
  • Colistin / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Female
  • Gram-Negative Bacteria / isolation & purification
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Colistin