Impact of colistin plasma levels on the clinical outcome of patients with infections caused by extremely drug-resistant Pseudomonas aeruginosa

Background: Colistin has a narrow therapeutic window with nephrotoxicity being the major dose-limiting adverse effect. Currently, the optimal doses and therapeutic plasma levels are unknown. Methods: Prospective observational cohort study, including patients infected by colistin-susceptible P. aeruginosa treated with intravenous colistimethate sodium (CMS). Clinical data and colistin plasma levels at steady-state (Css) were recorded. The primary and secondary end points were clinical cure and 30-day all-cause mortality. Results: Ninety-one patients were included. Clinical cure was observed in 72 (79%) patients. The mean (SD) Css was 1.49 (1.4) mg/L and 2.42 (1.5) mg/L (p = 0.01) in patients who achieved clinical cure and those who not, respectively. Independent risk factors for clinical failure were male sex (OR 5.88; 95% CI 1.09–31.63), APACHE II score (OR 1.15; 95% CI 1.03–1.27) and nephrotoxicity at the EOT (OR 9.13; 95% CI 95% 2.06–40.5). The 30-day mortality rate was 30.8%. Risk factors for 30-day mortality included the APACHE II score (OR 1.98; 95% CI 1–1.20), the McCabe score (OR 2.49; 95% CI 1.14–5.43) and the presence of nephrotoxicity at the end of treatment (EOT) (OR 3.8; 95% CI 1.26–11.47). Conclusion: In this series of patients with infections caused by XDR P. aeruginosa infections, Css is not observed to be related to clinical outcome.This work was supported by Fondo de Investigación Sanitaria (FIS) from Instituto de Salud Carlos III, Spanish Ministry of Health, Grant number PS09/01634 and from Spanish Ministry of Health and Social Policy, General Pharmacy Subdirection, Grant numbers EC10-165 and EC11-318. This study also received funding from European Regional Development Fund (FEDER: “A way of making Europe”). NB was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III and cofinanced by the European Development Regional Fund "A way to achieve Europe", Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015)