2025/03/04 by Xiaofen Liu, Lei Yang, Meihua Wang +10 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Antibiotic Resistance in Bacteria #Antibiotics Pharmacokinetics and Efficacy #Nosocomial Infections in ICU
paper · pdf · doi:10.1093/jacamr/dlaf023
openalex publication_date 2025/03/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
Abstract 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.