title: The impact of polymyxin B dosage on in-hospital mortality of patients treated with this antibiotic.
abstract: OBJECTIVE
  To assess the impact of dosage on in-hospital mortality of patients receiving intravenous polymyxin B.
  
  
  METHODS
  A retrospective cohort study was performed from January 2003 to December 2009. Patients ≥ 18 years receiving intravenous polymyxin B for ≥ 72 h were analysed. Clinical covariates were assessed and data were retrieved from medical records. Subgroup analyses were performed in patients with microbiologically confirmed infections and in patients with bacteraemia. Renal toxicity was also assessed. Logistic regression models (LRMs) were performed for the entire cohort and subgroups.
  
  
  RESULTS
  A total of 276 patients were included. The overall in-hospital mortality was 60.5% (167 of 276). The final LRM showed that severe sepsis or septic shock [adjusted odds ratio (aOR) 4.07; 95% confidence interval (CI) 2.22-7.46], presence of mechanical ventilation (aOR 3.14; 95% CI 1.73-5.71), Charlson co-morbidity score (aOR 1.25; 95% CI 1.09-1.44) and age (aOR 1.02; 95% CI 1.01-1.04) were independently associated with increased in-hospital mortality, while ≥ 200 mg/day polymyxin B was associated with lower risk for this outcome (aOR 0.43; 95% CI 0.23-0.79). The effect of ≥ 200 mg/day polymyxin B on in-hospital mortality was higher in both subgroups (microbiologically documented infections and bacteraemia). Patients receiving ≥ 200 mg/day of polymyxin B had significantly higher risk of severe renal impairment.
  
  
  CONCLUSIONS
  A dosage of ≥ 200 mg/day polymyxin B was associated with lower in-hospital mortality. The benefit of these higher doses outweighed the risk of severe renal dysfunction during therapy. Large prospective studies including pharmacokinetic/pharmacodynamic analysis are still required to define the best dosage regimens of polymyxin B.
authors.affiliation: Infection Control Service, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Elias
authors.forename: Daniele
authors.initials: D
authors.lastname: Konzen
authors.forename: Juliana M
authors.initials: JM
authors.lastname: Krebs
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Zavascki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016470:Bacteremia / Q000188:drug therapy / Q000401:mortality; D001424:Bacterial Infections / Q000188:drug therapy* / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011112:Polymyxin B / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D011112:Polymyxin B