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Table 3 Studies comparing index test to a composite reference standard

From: Systematic review of studies investigating ventilator associated pneumonia diagnostics in intensive care

Reference Study population Index test Reference test Results (95% confidence intervals where available)
Country n =  Mean age M:F ratio
Charles et al. [53] France 90 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 49 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 91 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 39 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 2080 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 459 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 162 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 82 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 150 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 77 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 54 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) RPDMIa 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 168 NR NR CDC definition (2013) CPIS ≥ 7 and miniBAL culture >  = 104 CFU/mL Sens = 37%
Spec = 100%
  1. aRPDMI score: radiological progression, purulent secretions, duration of mechanical ventilation, immunosuppression