Table 3 Studies comparing index test to a composite reference standard

Charles et al. [53]

France

61.1

2.3

Serum PCT (day of first suspicion of clinical infection)

All of (1) new lung infiltrate on the chest X-ray; (2) ETA culture > 10⁶ CFU/mL; (3) CPIS ≥ 6 points; (4) at least 2 SIRS criteria

Sens = 65.2%

Spec = 83%

Chen et al. [52]

China

54

1.45

Serum PCT

serum CRP

CPIS

(1) Persistent or new invasive shadows in the lung; (2) At least two below items: temperature more than 38 °C or less than 36 °C; leucocyte count > 10 or < 4 × 10/L; purulent sputum; (3) Any of the item below: bronchoscopic aspiration or sputum specimen bacterial culture +++ or pathogenic bacteria cultured from blood

CRP

Sens = 68.0%

Spec = 58.3%

PCT

Sens = 60.0%

Spec = 87.5%

CPIS

Sens = 72.0%

Spec = 75.0%

Grover et al. [44]

UK

59

1.5

7 marker score: BAL/blood ratio mTREM-1 and mCD11b, BALF sTREM-1, IL-8 and IL-1b, and serum CRP and IL-6

VAP was predefined as CPIS > 5 and

positive BALF microbiology. Non-VAP was predefined as CPIS score < 6 and negative microbiology

Sens = 88.9%

Spec = 100%

Jovanovic et al. [64]

Serbia

47.9

5.5

Serum sCD14-ST

PCT

CRP

Leucocyte count

New persistent pulmonary infiltrates (not otherwise explainable) on CXR > 48 h after admission to the ICU, PLUS one systemic and two pulmonary criteria

Systemic criteria

Fever > 38 °C, white cell count < 4000 WBC/mm³ or > 12,000 WBC/mm³

altered mental status, with no other recognized cause (for adults older than 70 years of age)

Pulmonary criteria

new onset of purulent sputum (or a change in the character of the sputum, increased respiratory secretions or increased suctioning requirements),

worsening gas exchange (desaturations, increased oxygen requirements or increased ventilator demand),

new onset or worsening cough, and dyspnoea, tachypnoea, rales or bronchial breath sounds

sCD14-ST

AUROCC = 0.908

PCT

AUROCC = 0.863

CRP

AUROCC = 0.703

Leucocyte count AUROCC = 0.668

Klein Klouwenberg et al. [61]

Netherlands

62

1.6

CDC surveillance definition (2013)

Existing local surveillance criteria divided into possible, probable, and definite VAP

Possible (CPIS > 6, dubious abnormalities on radiographic examination, semi-quantitative culture from respiratory secretions—ETA or bronchoscopic aspirate)

Probable (CPIS > 6, new or progressive infiltrates, consolidation, cavitation or pleural effusion, BAL culture > 10⁴ CFU/mL or PSB culture > 10³ CFU/mL OR positive blood culture with pathogen also isolated from airway culture)

Definite (CPIS > 6, new or progressive infiltrates, consolidation, cavitation or pleural effusion OR radiographic evidence of lung abscess or empyema, histopathologic evidence of pneumonia (abscess with PMN concentration and positive tissue culture) OR if empyema, positive culture of aspirate))

Sens = 22% (for probable or definite reference standard VAP)

Spec = 98%

Klompas et al. [62]

USA

55.3

1.5

Objective algorithm of electronic patient record (precursor of CDC surveillance definition 2013)

CDC definition (2008)

Sens = 95

Spec = 100

Liu et al. [68]

China

61.6

1.5

BAL neutrophil intracellular organisms

(1) histopathological diagnosis performed within 7 days of bronchoscopy OR

(2) BAL culture ≥ 10⁴ CFU/mL, and responded to antibiotic therapy OR

(3) rapid cavitation of the lung infiltrate on chest x-ray film or CT scan associated with responded to antibiotic therapy OR

(4) positive culture of the pleural effusion, and the same microorganisms isolated from cultures of pleural effusion and lower respiratory tract secretions, and responded to antibiotic therapy OR

(5) complete resolution with appropriate antibiotic therapy with no other disease explaining chest radiograph abnormality

Sens = 94.12%

Spec = 88.33%

Mauri et al. [71]

Italy

59

2.6

BAL fluid pentraxin 3

1. New and persistent radiographic infiltrates associated with at least two of the following:

a. Internal body temperature > 38 °C,

b. White blood cells count > 12,000 or < 4000 cells/mm³ and/or

c. Purulent tracheobronchial secretions; AND

2. BAL culture > 10⁴ CFU/mL and/or significant noncontaminant viral load

Sens = 92%

Spec = 60%

Medford et al. [72]

UK

62.3

1.5

ETA culture > 10⁵ or BAL culture > 10⁴

New/progressive CXR infiltrates without other

obvious cause in patients mechanically ventilated for more than 4 days in the ICU and at least 2 of the following: temperature ≥ 38 °C or ≤ 35 °C, white cell count ≥ 12 or ≤ 4 × 10⁹/L, purulent tracheobronchial secretions, with increasing oxygen requirements, computed tomography evidence of a rapidly cavitating infiltrate, positive pleural fluid culture and/or histological evidence of neutrophilic alveolitis, bronchiolitis, and consolidation in conjunction with pleural fluid microbiology, CT evidence, and histological evidence

BAL

Sens = 64.1%

Spec = 83.0%

ETA

Sens = 42.6%

Spec = 33.7%

Textoris et al. [78]

France

30.75

NR

blood Transcriptome DNA microarray analysis (HuSG9 k)

purulent bronchial sputum; body temperature more than 38 °C or less than 36 °C; leukocytes more than 10 × 10⁹/L or less than 4 × 10⁹/L; chest radiograph showing new or progressive infiltrates; BAL culture ≥ 10⁴ CFU/mL, or ETA culture ≥ 10⁶ CFU/mL

Sens = NR

Spec = NR

Vernikos et al. [80]

Greece

72

1.3

1) Johansen criteria,

2) Modified CPIS > 6 REF

3) Johansen criteria combined with relative neutrophil count

4) CPIS > 6 combined relative neutrophil count

5) RPDMI^a score

CDC definition (2015)

Johansen criteria

Sens = 85.7%

Spec = 73.7%

Modified CPIS > 6

Sens = 62.9%

Spec = 73.7%

Johansen criteria combined with relative neutrophil count (20% cut off)

Sens = 67.6%

Spec = 81.3%

CPIS > 6 combined relative neutrophil count (20% cut off)

Sens = 47.1%

Spec = 81.3%

RPDMI score

Sens = 94.3%

Spec = 84.2%

Waltrick et al. [81]

Brazil

NR

NR

CDC definition (2013)

CPIS ≥ 7 and miniBAL culture >  = 10⁴ CFU/mL

Sens = 37%

Spec = 100%