Inhaled Polymyxin E to Prevent VAP

Ventilator associated pneumonia is the most common manifestation of hospital acquired infections in ICU. The incidence of ventilator-associated pneumonia in patients receiving mechanical ventilation is as high as 20% -71%, which can lead to increased systemic antibiotic use, prolonged mechanical ventilation time and ICU stay, and increased treatment costs. In addition, ventilator-associated pneumonia is also the main cause of hospital infection related deaths in critically ill patients.

However, there is a certain buffer time for patients to develop ventilator-associated pneumonia after receiving endotracheal intubation. Previous studies have found that the peak incidence occurs after 7 days of mechanical ventilation, so there is an opportunity for early treatment to prevent infection. Despite the implementation of numerous preventive measures for ventilator-associated pneumonia over the decades, such as reducing sedation and withdrawal protocols, patient positioning, oral care, prophylactic probiotics, prophylactic antibiotics, and the use of silver plated endotracheal tubes. Among them, the research on the preventive use of antibiotics has a history of over 30 years and is a topic of substantial debate. Prophylactic use of antibiotics includes systemic application and local nebulization inhalation, and inhaled antibiotics may be an effective measure for preventing ventilator-associated pneumonia. Potential extensively drug-resistant Gram negative (XDR-GN) bacteria, such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, are common pathogens causing VAP in ICU. The mortality rate of VAP caused by XDR-GN pathogen may be higher than 70%. With the increasing incidence of multidrug-resistant microorganisms, nebulized or inhaled aminoglycoside antibiotics are often used as empirical or definitive treatment for VAP in ICU patients. The previous group of antibiotics, polymyxin, has returned to the view of medical staff. Sodium polymyxin E methanesulfonate has been used as a salvage therapy for XDR-GN bacteria causing pneumonia, demonstrating its activity against XDR-GN causing VAP in critically ill patients. The guidelines of the Infectious Diseases Society of America (IDSA) on hospital acquired pneumonia also indicate that patients with Gram negative pneumonia caused by drug-resistant bacteria are sensitive to polymyxins. In this randomized controlled study, we aim to investigate the effect of prophylactic use of polymyxin E nebulized inhalation on the incidence of VAP.


Eligibility Criteria:
Inclusion Criteria:

1. Age \>18 years old
2. Patients with brain injury admitted to ICU (including brain injury caused by trauma, cerebral hemorrhage, cerebral infarction, and cardiac arrest)
3. GCS score\<12 points
4. Mechanical ventilation time ≥ 48 hours
5. Sign informed consent

Exclusion Criteria:

1. Existing lung diseases that require long-term inhaled medication treatment.
2. Lower respiratory tract infection at admission.
3. New or persistent infiltration on chest imaging within 48 hours after admission.
4. Expected removal of endotracheal tube within the next 24 hours.
5. Mechanical ventilation time before enrollment exceeds 96 hours.
6. Tracheostomy patients.
7. Current or recent use of polymyxin E (within 24 hours).
8. Allergy to polymyxin E.
9. Allergic pregnant or lactating women.
10. Severe neuromuscular lesions.
11. Severe other organ dysfunction. Expected short-term death (48 hours) or palliative treatment.
12. Late stage solid organ or blood system tumors. Expected survival\<30 days. 13. Participate in other clinical studies within 30 days