Efficacy of polymyxin B against different pathogens in carbapenem-resistant gram-negative bacterial pneumonia and its relationship with alveolar epithelial lining fluid concentration: a prospective cohort study

Background The relationship between polymyxin B (PMB) concentrations in alveolar epithelial lining fluid (ELF) and pathogen clearance in carbapenem-resistant Gram-negative bacilli (CRGNB) pneumonia remains unclear. This study evaluated the efficacy of combined nebulized and intravenous PMB and its association with ELF exposure.Methods This prospective cohort study included 104 patients with CRGNB pneumonia caused by Pseudomonas aeruginosa (CRPA, n=34), Acinetobacter baumannii (CRAB, n=38), and Klebsiella pneumoniae (CRKP, n=32) receiving nebulized PMB (25 mg every 12 h) plus intravenous PMB (1.25 mg/kg every 12 h) for approximately 14 days. PMB ELF concentrations were measured by the urea dilution method. The primary outcome was bacterial clearance rate; secondary outcomes included time to bacterial clearance, clinical efficacy, fever normalization, 28-day survival, CRGNB-related mortality, inflammatory markers and adverse events.Results Bacterial clearance rates (70.59% CRPA, 71.05% CRAB, 78.12% CRKP) and clinical efficacy rates (70.59%, 81.58%, 78.12%) showed no significant intergroup differences (all p > .05). CRKP had a shorter time to clearance than CRAB (median, 5.00 vs. 7.00 days, p = .004). No significant differences were observed in 28-day survival, CRGNB-related mortality, or adverse events. PMB ELF trough concentration and mechanical ventilation duration were independent predictors of bacterial clearance (both p < .05). Higher PMB ELF peak and trough concentrations were associated with shorter clearance/replacement time (both p < .05).Conclusion The combined PMB regimen achieves favorable bacterial clearance and clinical efficacy in CRGNB pneumonia. Higher local pulmonary PMB exposure was associated with improved bacteriological outcomes, supporting ELF-guided dose optimization.