Different Methods of Aerosolized Polymyxin B Inhalation for Treating Carbapenem-Resistant Gram-Negative Bacterial Pneumonia.
A Prospective Clinical Study on Different Methods of Aerosolized Polymyxin B Inhalation for the Treatment of Carbapenem-Resistant Gram-Negative Bacterial Pneumonia
Fujian Medical University Union Hospital
144 participants
Feb 1, 2023
OBSERVATIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria4
- 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.
Exclusion Criteria4
- 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.
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Interventions
* 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.
Locations(1)
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NCT07086391