Outcomes
Outcome | Definition |
---|---|
Clinical success (primary outcome) | Composite of:
|
14-day all-cause mortality | |
28-day all-cause mortality | |
Clinical success without modification | Clinical success, as defined above, but any modification to the antibiotic treatment not permitted by protocol will also be considered as a failure. This will include any change or addition of antibiotics not permitted by the study protocol during the first 10 days after randomisation. Early discontinuation of antibiotic treatment will not be considered as a failure. |
Time to defervescence | Time to reach a temperature of <38°C with no recurrence for 3 days |
Time to weaning from mechanical ventilation | Days from randomisation to weaning for patients with VAP weaned alive |
Time to hospital discharge | Days to hospital discharge among patients discharged alive |
Change in functional capacity | Assessed from baseline status before infection onset to discharge from hospital Function capacity will be classified into 3 grades:
|
Microbiological failure | Isolation of the initial isolate (phenotypically identical) in a clinical sample (blood or other) 7 days or more after start of treatment or its identification in respiratory samples (see Data collection and microbiological sampling and table 4 below) |
Superinfection | New clinically or microbiologically documented infections by CDC criteria within 28 days, any and specifically those caused by newly acquired carbapenem-resistant or colistin-resistant Gram-negative bacteria |
Resistant colonisation | Colonisation by phenotypically newly acquired carbapenem-resistant or colistin-resistant Gram-negative bacteria. Assessed by rectal surveillance (see Data collection and microbiological sampling and table 4 below) |
CDI | Diarrhoea with a positive Clostridium difficile toxin test |
Renal failure | Renal failure using the RIFLE criteria39 at days 14 and 28 relative to the day of randomisation |
Seizures | Seizures or other neurological adverse events including critical illness neuropathy |
Other adverse events | Requiring treatment discontinuation |
CDC, Centers for Disease Control and Prevention; CDI, Clostridium difficile infection; FiO2, fractional inspired oxygen; HAP, hospital-acquired pneumonia; PaO2, arterial oxygen tension; SOFA, Sequential Organ Failure Assessment; VAP, ventilator-associated pneumonia.