Colistin Methanesulfonate Sodium Inhalation for Prophylaxis of Ventilator-Associated Pneumonia (CIVAP): A Prospective, Multicentre, Double-Blind, Randomized, Placebo-Controlled Trial
Previous studies have identified Acinetobacter baumannii (AB), Pseudomonas aeruginosa (PA), and Klebsiella pneumoniae (KP) as the predominant pathogens responsible for ventilator-associated pneumonia (VAP). The challenge of drug resistance, especially against carbapenem is intensifying, with variations noted across different regions. Multidrug-resistant organisms associated VAP (MDR-VAP) are increasing in frequency and are associated with significant morbidity, mortality, therefore imposes a heavy burden on the healthcare system. Colistin methanesulfonate sodium (CMS) has shown effectiveness against gram-negative bacteria, including carbapenem-resistant organisms (CRO) such as carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Klebsiella pneumoniae (CRKP). This trial aims to evaluate the efficacy of a 3-day course of inhaled CMS in lowering the incidence of VAP among patients undergoing invasive mechanical ventilation for at least two days and at high risk of MDR-VAP.
‣ Participants will be enrolled if they meet the following criteria:
• Age ≥18 years;
• Mechanical ventilation for more than two consecutive days (48 hours);
• Patient has high-risk factors for multidrug-resistant bacterial infections, which meet any of the following criteria:
‣ (1)History of antibiotic exposure within 30 days; (2)Hospitalization time\>5 days (120 hours); (3)Septic shock; (4) ARDS; (5)Accept renal replacement therapy; (6)Previous colonization of multidrug-resistant bacteria; 4. Informed consent of the patient or a proxy was written.
‣ Participants will be excluded in case of:
• Suspected or confirmed VAP at the inclusion day;
• Patient ventilated through an endotracheal tube for more than four consecutive days (96 hours);
• Expected that endotracheal intubation will be removed within the next 24 hours;
• Tracheostomy;
• Allergy to CMS;
• Patients has polymyxins medication history within 7 days or clinical indication for systemic CMS therapy at the inclusion day;
• Chronic kidney failure with baseline glomerular filtration ≤30 mL/min or Stage 3 classification AKI (KDIGO) (excluding patients undergoing renal replacement therapy);
• Expected survival time not exceeding 48 hours;
• Pregnancy or breastfeeding period;
⁃ Patients previously included in this study or are using any inhaled antibiotics or are participating in other clinical studies within 30 days.