Study Design:
A randomized, open-label, parallel-group clinical trial comparing the efficacy and safety of jet nebulization versus vibrating mesh nebulization of sulfate polymyxin B in mechanically ventilated patients with carbapenem-resistant Gram-negative bacterial pneumonia.
Participants:
144 patients (72 per group) will be enrolled from December 2023 to December 2025.
Interventions:
Group A: 25mg polymyxin B + 5ml sterile water via jet nebulizer (respirator-assisted).
Group B: 25mg polymyxin B + 5ml sterile water via vibrating mesh nebulizer (respirator-assisted).
Both groups receive additional intravenous polymyxin B (2.0mg/kg loading dose, followed by 1.25mg/kg every 12h) starting 12h after nebulization.
Treatment duration: 14 days.
Key Procedures:
Nebulization parameters: Fixed ventilator settings (SIMV+PSV mode, tidal volume 8ml/kg, PEEP 6cmH₂O).
Bronchoalveolar lavage (BAL) and blood sampling:
BAL fluid (BALF) and blood collected pre-nebulization (baseline), 1h post-nebulization, and at steady-state (days 3-7).
BALF analyzed for polymyxin B concentration, urea nitrogen, and inflammatory mediators (IL-6, TNF-α, etc.).
Primary Outcomes:
Clinical efficacy:
Total response rate (cure + improvement). 28-day survival rate. Time to fever resolution and bacterial clearance.
Drug exposure:
Polymyxin B concentration in alveolar epithelial lining fluid (ELF) and blood.
Secondary Outcomes:
Inflammatory response: Changes in BALF and serum IL-6, TNF-α, CRP levels.
Safety:
Nephrotoxicity (changes in serum creatinine/urea nitrogen). Airway complications (bronchospasm incidence).
Assessment Timeline:
Clinical monitoring: Daily evaluation of vital signs, sputum volume, and ventilator parameters.
Lab tests: Blood tests (hematology, renal function, inflammatory markers) at baseline, days 3/7/14.
Microbiological evaluation: Sputum cultures on days 3/7/14.
Statistical Analysis:
Efficacy and safety endpoints compared between groups using t-tests or chi-square tests.
A p-value \<0.05 will be considered statistically significant.
Pneumonia diagnosed per Chinese Thoracic Society criteria (radiographic + clinical evidence).
Sputum culture-confirmed carbapenem-resistant Gram-negative bacteria susceptible to polymyxin B.
≥3 days of aerosolized polymyxin B therapy.
Mechanically ventilated with an artificial airway.
Polymyxin B aerosol use planned for <3 days.
Terminal status (life expectancy <48h).
Severe liver/kidney dysfunction (ALT/AST >5× ULN; eGFR <30 mL/min).
No informed consent.
Mechanically ventilated adults with carbapenem-resistant Gram-negative bacterial pneumonia (e.g., Pseudomonas aeruginosa) confirmed by sputum culture and susceptible to polymyxin B. Participants must receive ≥3 days of aerosolized polymyxin B via endotracheal tube/tracheostomy. Exclusions: life expectancy \<48h, severe liver/kidney dysfunction, or lack of informed consent.
Cohort
Prospective
Polymyxin B Sulfate 25mg Jet Nebulization / Vibrating Mesh Nebulization
Device* Group A: 25mg polymyxin B sulfate dissolved in 5ml sterile water, administered via jet nebulizer under mechanical ventilation. * Group B: 25mg polymyxin B sulfate dissolved in 5ml sterile water, administered via vibrating mesh nebulizer under mechanical ventilation.
Clinical efficacy
Percentage of patients with cure or improvement based on symptom resolution, microbiological clearance, and radiographic findings.
28-Day Survival Rate
Survival status assessed at 28 days post-treatment initiation.
Microbiological Clearance Rate
Eradication or replacement of carbapenem-resistant pathogens.
Click on the lead sponsor to view all of their trials.
