Prospective observational study of the impact of plasma colistin levels in patients with carbapenem-resistant Acinetobacter baumannii pneumonia

Objectives: Colistin, an important drug to treat carbapenem-resistant Acinetobacter baumannii (CRAB) infections, has a narrow therapeutic window with nephrotoxicity. This study was conducted 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. Patients with CRAB pneumonia were treated with intravenous colistin methanesulfonate (CMS) at 2.5-5.0 mg/kg/day. On Days 3 and 4, plasma colistin and CMS concentrations were determined by six serial blood samples (immediately prior to dosing and 1 h and 4 h after the end of infusion).

Results: The 25 patients included in the analysis had hospital-acquired pneumonia caused by CRAB. Nephrotoxicity occurred in five patients (20%) on Day 7. There was no difference in clinical characteristics of patients with or without nephrotoxicity. The maximum plasma CMS concentration (mean ± standard deviation) was significantly higher in patients with nephrotoxicity on Day 7 than those without nephrotoxicity (15.3 ± 4.2 mg/L vs. 8.3 ± 3.8 mg/L; P = 0.014). The maximum plasma colistin concentration (C_max,col) was significantly higher in the nephrotoxicity group on Day 7 (4.8 ± 2.0 mg/L vs. 2.1 ± 1.0 mg/L; P = 0.002). C_max,col was lower in patients with microbiological failure than those without microbiological failure (1.92 mg/L vs. 3.01 mg/L; P = 0.038).

Conclusion: This study confirmed that plasma levels of CMS and colistin, especially maximum levels, are important for predicting nephrotoxicity in patients with CRAB pneumonia. [ClinicalTrials.gov ID NCT02482961].