Table 1

Inclusion criteria for infections

Type of infectionDefinition
BSIGrowth of the relevant bacteria in one or more blood culture bottles accompanied by the SIRS within 48 h of blood culture taken time. BSIs can be either primary or secondary to any other source of infection.
VAP or HAPPneumonia fulfilling CDC/NHSN surveillance definition of healthcare-associated infection for pneumonia with specific laboratory findings (PNU2) with modifications to the laboratory criteria.29 Ventilator-associated pneumonia will be defined in persons who had a device to assist or control respiration continuously through a tracheostomy or by endotracheal intubation within the 48 h period before the onset of infection. BAL will not be performed routinely for the purposes of the trial. The specific criteria required for diagnosis of pneumonia will be all of the following:

  1. Chest radiograph with new or progressive and persistent infiltrate, consolidation or cavitation;

  2. At least 1 of the following signs of sepsis: fever >38°C with no other recognised cause; leucopaenia <4000 WCC/mm3 or leucocytosis >12 000 WCC/mm3; for adults aged >70 years, altered mental status with no other recognised cause;

  3. At least 1 of the following respiratory signs/symptoms: new onset of purulent sputum or change in character of sputum or increased respiratory secretions or increased suctioning requirements; new onset or worsening cough or dyspnoea or tachypnoea >25 breaths per minute; rales or bronchial breath sounds; worsening gas exchange, including O2 desaturations, PaO2/FiO2 <240 or increased oxygen requirements;

  4. Laboratory criterion: growth of the relevant bacteria in culture of sputum, tracheal aspirate, BAL or protected specimen brushing. For any lower respiratory secretion other than BAL or PSB, the respiratory sample has to contain >25 neutrophils and <10 squamous epithelial cells per low power field, identified by Gram stain.

Probable VAPPneumonia fulfilling the CDC/NHSN 2013 revised surveillance definition, omitting the criterion of antimicrobial treatment before randomisation and modifying the microbiological criteria:30

  1. Mechanical ventilation for ≥3 calendar days;

  2. Worsening oxygenation, following ≥2 calendar days of stable or decreasing FiO2 or PEEP, presenting as:

    • Minimum daily FiO2 values increase ≥0.20 (20 points) over baseline and remain at or above that increased level for ≥2 calendar days OR

    • Minimum daily PEEP values increase ≥3 cm H2O over baseline and remain at or above that increased level for ≥2 calendar days.

  3. Temperature >38°C or <36°C, OR white cell count ≥12 000 cells/mm3 or ≤4000 cells/mm3;

  4. Purulent respiratory secretions AND positive respiratory culture; OR positive culture of pleural fluid. For any lower respiratory secretion other than BAL or PSB, the respiratory sample has to contain >25 neutrophils and <10 squamous epithelial cells per low power field, identified by Gram stain.

UrosepsisPositive urine culture with relevant bacteria ≥105 CFU/mL with pyuria, accompanied by the SIRS within 48 h of taken time and no other explanation for SIRS

  • BAL, bronchoalveolar lavage; BSI, bloodstream infection; CDC/NHSN, Centers for Disease Control and Prevention/ National Healthcare Safety Network; FiO2, fractional inspired oxygen; HAP, healthcare-associated pneumonia; PaO2, arterial oxygen tension; PEEP, positive end-expiratory pressure; PSB, protected specimen brush; SIRS, systemic inflammatory response syndrome; VAP, ventilator-associated pneumonia; WCC, white cell count.