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. 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,C-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. (C) 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.