Table 3

Outcomes

OutcomeDefinition
Clinical success (primary outcome)Composite of:
  • Patient alive

  • Systolic blood pressure >90 mm Hg without need for vasopressor support

  • Stable or improved SOFA score, defined as:

    • For baseline SOFA ≥3: a decrease of at least 30%

    • For baseline SOFA <3: stable or decreased SOFA score

  • For patients with HAP/VAP, PaO2/FiO2 ratio stable or improved

  • For patients with bacteraemia, no growth of the initial isolate in blood cultures taken on day 14 if patient still febrile

14-day all-cause mortality
28-day all-cause mortality
Clinical success without modificationClinical 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 defervescenceTime to reach a temperature of <38°C with no recurrence for 3 days
Time to weaning from mechanical ventilationDays from randomisation to weaning for patients with VAP weaned alive
Time to hospital dischargeDays to hospital discharge among patients discharged alive
Change in functional capacityAssessed from baseline status before infection onset to discharge from hospital
Function capacity will be classified into 3 grades:
  1. Independent

  2. Need for assistance for activities of daily living

  3. Bedridden

Microbiological failureIsolation 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)
SuperinfectionNew 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 colonisationColonisation 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)
CDIDiarrhoea with a positive Clostridium difficile toxin test
Renal failureRenal failure using the RIFLE criteria39 at days 14 and 28 relative to the day of randomisation
SeizuresSeizures or other neurological adverse events including critical illness neuropathy
Other adverse eventsRequiring 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.