Evaluating a Novel Bacteriophage Cocktail for Eradicating Pseudomonas aeruginosa Biofilms in Ventilator-Associated Pneumonia

Abstract

Background: Ventilator-associated pneumonia caused by Pseudomonas aeruginosa remains difficult to treat because of multidrug resistance and biofilm formation, which reduce antibiotic penetration and contribute to persistent infection in mechanically ventilated patients. Objective: To evaluate the efficacy of adjunctive nebulized bacteriophage cocktail therapy in reducing P. aeruginosa biofilm burden and improving microbiological and clinical outcomes in ventilator-associated pneumonia. Methods: A parallel-group randomized controlled trial was conducted in tertiary care intensive care units over five months. Seventy-two mechanically ventilated adults with microbiologically confirmed P. aeruginosa ventilator-associated pneumonia and evidence of biofilm formation were randomized to receive either standard culture-guided antibiotic therapy plus nebulized bacteriophage cocktail twice daily for 14 days or standard care alone. Primary outcomes were biofilm biomass reduction and microbiological clearance; secondary outcomes included duration of mechanical ventilation, Clinical Pulmonary Infection Score, and intensive care unit stay. Results: The final analyzed cohort included 63 participants. Day-14 biofilm biomass was significantly lower in the intervention group than in controls (0.62 ± 0.18 vs 0.94 ± 0.22 OD units; p<0.001). Culture negativity was higher with bacteriophage therapy (75.0% vs 45.2%; p=0.01). The intervention group also had shorter mechanical ventilation duration, lower day-14 Clinical Pulmonary Infection Score, and reduced intensive care unit stay (p<0.05 for all). Conclusion: Adjunctive nebulized bacteriophage cocktail therapy improved biofilm reduction, microbiological clearance, and short-term clinical outcomes in P. aeruginosa ventilator-associated pneumonia.