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.
Age ≥18 years;
Mechanical ventilation for more than two consecutive days (48 hours);
Suspected or confirmed VAP at the inclusion day;
Patient ventilated through an endotracheal tube for more than four consecutive days (96 hours);
None
Parallel
Colistimethate sodium (CMS)
DrugCMS (colistimethate sodium, 75mg, solubilized in 4 mL 0.9% saline), twice daily. Nebulization will be performed using a vibrating mesh nebulizer (Aeroneb solo, Aerogen, Galway, Ireland) placed in the inspiratory limb of the ventilator tubing, behind the Y-piece, and continued until the nebulizer deposit becomes dry for three consecutive days of mechanical ventilation. To ensure the experiment is conducted under blind conditions, the Nebulizer will be covered by stickers. A filter will be placed on the expiratory limb to protect the ventilator.
The incidence of a first VAP episode from randomization to day 28
calculated as the ratio of the number of patients diagnosed VAP divided by the number of randomized patients in each group
incidence of a first MDR-VAP episode from randomization to day 28
Calculated as the ratio of the number of patients diagnosed VAP divided by the number of randomized patients in each group
Incidence density of adjudicated VAP from randomisation to day 28
per 1000 patient-days of invasive mechanical ventilation
Incidence of gram-negative bacteria-related VAP with in vitro susceptibility to CMS from randomisation to day 28
the incidence of ventilator-associated pneumonia due to gram-negative bacteria with in vitro susceptibility to colistin
The number of antibiotic-days from randomisation to day 28
the sum of the number of systemic antibiotic treatments received each day
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