Carbapenem-Resistant Enterobacteriaceae Infection, Pneumonia - Bacterial
Conditions
Brief 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.
Interventions
DEVICEPolymyxin B Sulfate 25mg Jet Nebulization / Vibrating Mesh Nebulization
* 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.
Sponsors
Fujian Medical University Union Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* 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 criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical efficacy | Baseline (pre-treatment); End of Treatment (EOT, 14 days after starting polymyxin B) | Percentage of patients with cure or improvement based on symptom resolution, microbiological clearance, and radiographic findings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 28-Day Survival Rate | Baseline (pre-treatment); End of Treatment (EOT, 28 days after starting polymyxin B) | Survival status assessed at 28 days post-treatment initiation. |
| Microbiological Clearance Rate | Baseline (pre-treatment); End of Treatment (EOT, 14 days after starting polymyxin B) | Eradication or replacement of carbapenem-resistant pathogens. |
Countries
China
Outcome results
None listed