Prospective Observational Study of the Impact of Plasma Colistin Levels in Patients with Carbapenem-Resistant Acinetobacter baumannii pneumonia.

Abstract Objectives Colistin, an important drug to treat carbapenem-resistant Acinetobacter baumannii (CRAB) infections, has a narrow therapeutic window with nephrotoxicity. We conducted this study to determine the importance of colistin concentrations in predicting nephrotoxicity when treating CRAB pneumonia with colistin. Methods A prospective cohort study was performed in one teaching hospital from May 2015 to January 2018. The patients with CRAB pneumonia were treated with colistin methane-sulfonate (CMS) IV at 2.5 – 5mg/kg/day. On the third and fourth day, plasma colistin and CMS concentrations were determined by 6 serial blood samples (immediately prior to dosing, 1 h, and 4 h after the end of drug infusion). Results The 25 patients included in the analysis had hospital-acquired pneumonia with CRAB. Nephrotoxicity occurred in five patients (20.0%) on day 7. There was no difference in the clinical characteristics of the patients with or without nephrotoxicity. The maximum plasma CMS level (mean ± SD) was significantly higher in patients with nephrotoxicity on day 7 than those without nephrotoxicity, at 15.3 ± 4.2 vs. 8.3 ± 3.8 mg/L (p = 0.014). The maximum plasma colistin level (Cmax,col) was significantly higher in the nephrotoxicity group on day 7, at 4.8 ± 2.0 vs. 2.1 ± 1.0 mg/L (p = 0.002). Cmax,col was lower in patients with microbiological failure than those without microbiological failure (1.92 vs. 3.01 mg/L; p = 0.038). Conclusions This study confirmed that the plasma levels of CMS and colistin, especially the maximum levels, were important for predicting nephrotoxicity in patients with CRAB pneumonia.