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

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... s 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. Conclusion: 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.