The purpose of this study is to systematically evaluate the efficacy and safety of bacteriophage cocktail therapy in patients with ventilator-associated pneumonia caused by Gram-negative bacterial infections.

This study investigates the clinical application of bacteriophage therapy in severe infections through a prospective, randomized, multi-center trial targeting ventilator-associated pneumonia (VAP) caused by multidrug-resistant Gram-negative bacteria. The trial will comprehensively assess the efficacy, safety, and applicability of inhaled bacteriophage cocktail therapy, providing high-quality clinical evidence to support the establishment of an evidence-based framework for phage therapy. The primary endpoint is clinical response rate, with secondary endpoints including bacterial clearance and 28-day mortality, aiming to determine the therapeutic potential and clinical value of phage cocktails in VAP treatment.

Inclusion Criteria:

1. Diagnosed with ventilator-associated pneumonia (VAP);
2. Identified infection with MDR Klebsiella pneumoniae, Acinetobacter baumannii, or Pseudomonas aeruginosa via MROSE evaluation and antimicrobial susceptibility testing (AST) from this or other tertiary hospitals;
3. Aged 18 to 85 years;
4. Written informed consent obtained from the patient or legal guardian.

Exclusion Criteria:

1. Pregnant or breastfeeding women;
2. FiO₂ ≥ 70% or PEEP ≥ 15 cmH₂O;
3. Hemodynamic instability (vasopressor dose increased by ≥30% in the last 6 hours or norepinephrine > 0.5 μg/kg/min);
4. Known allergy to phage components.