Aerosolized delivery resulting in high polymyxin B concentration levels in epithelial lining fluid ensures efficacy in ventilator-associated pneumonia
Xiaofen Liu, Lei Yang, Meihua Wang, Yu Wang, Beining Guo, Chuhan Zhang, Xingyi Qu, Chenxue Guo, Yaxin Fan, Hailan Wu, Xin Li, Jin Hu, Jing ZhangAbstract
Background
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.
Methods
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.
Results
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 (AUC24h,ELF) ranged from 283.6 to 1872.9 mg•h/L.
Conclusions
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.