Aerosolized delivery resulting in high polymyxin B concentration levels in epithelial lining fluid ensures efficacy in ventilator-associated pneumonia.

Abstract

<h4>Background</h4>Aerosolized polymyxin B delivery was a promising approach for the treatment of ventilator-associated pneumonia (VAP). However, there were little data on the concentrations of polymyxin B in epithelial lining fluid (ELF), which impedes the optimal use of aerosolized polymyxin B in clinics.<h4>Methods</h4>We present four cases of patients diagnosed with VAP caused by Gram-negative bacteria, who enrolled in a prospective, therapeutic drug monitoring (TDM) study of polymyxin B. The patients were treated with aerosolized and intravenous administration of polymyxin B. Polymyxin B concentrations in both ELF and plasma were determined using validated LC-MS/MS methods.<h4>Results</h4>All four patients achieved bacterial eradication, with three of them reaching clinical improvement or cure. Following aerosol administration (25 or 50 mg, q12h) and intravenous infusion (50-100 mg, q12h) of polymyxin B, it was observed that the concentrations of polymyxin B in ELF were significantly higher in ELF (20.6-97.6 mg/L) compared to those in plasma (1.19-5.16 mg/L) during the steady sate. The area under the concentration-time curve for 24 h (AUC_24h,ELF) ranged from 283.6 to 1872.9 mg•h/L.<h4>Conclusions</h4>This study presented polymyxin B concentrations in ELF following aerosolized delivery, supporting its clinical use from a PK/PD perspective. Following combined aerosol and intravenous administration, polymyxin B achieved notably higher concentrations in ELF than those observed in plasma.