Skip to main content
  • Poster presentation
  • Published:

Biomarker-based exclusion of ventilator-associated pneumonia: a multicentre validation study


Ventilator-associated pneumonia (VAP) remains a leading cause of nosocomial infection in the ICU [1]. VAP is confirmed by positive microbiology in approximately one-third of patients with suspected VAP [2], implying that there is scope to improve antibiotic stewardship. In a single-centre study, bronchoalveolar lavage fluid (BALF) inflammatory mediators (in particular interleukin-1 beta (IL-1β)) [3] and neutrophil proteases [4] demonstrated potential as biomarkers to exclude VAP. We aimed to validate these findings in a multicentre study.


We conducted a prospective, multicentre observational study of 167 patients with clinically suspected VAP from 12 ICUs across the UK. VAP was confirmed by growth of a potential pathogen in BALF at >104 colony-forming units/ml. IL-1β, IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were measured in BALF by cytometric bead array. IL-6, IL-8, MMP-8, MMP-9 and HNE were measured in serum. Patients were dichotomised into VAP and non-VAP groups and receiver operating characteristics (ROC) curves were constructed for individual biomarkers and combinations of markers before optimum cutoff points were determined.


A total of 150 patients had paired semi-quantitative culture and biomarker results. Fifty-three (35%) patients had VAP and 97 (65%) patients formed the non-VAP group. All BALF biomarkers were significantly higher in the VAP group (P < 0.001). The area under the ROC curve for IL-1β was 0.81, for IL-8 was 0.736, for MMP-8 was 0.758, for MMP-9 was 0.785 and for HNE was 0.777. Using a cutoff value of 17 pg/ ml, IL-1β had a sensitivity of 96.2%, a specificity of 43.3%, a negative predictive value (NPV) of 95.5% and a post-test probability of 4.5% (95 CI: 1 to 16%). A combination of IL-1β and IL-8 excluded VAP with a sensitivity of 100%, a specificity of 44.3% and a NPV of 1. There was no significant difference in serum biomarkers between the VAP and non-VAP groups.


This study demonstrates that IL-1β effectively excludes VAP when validated in a multicentre study. The performance is further improved by the addition of IL-8, and the combination could form a rapid diagnostic assay to exclude VAP. Biomarker analysis appears to have the potential to improve antibiotic stewardship, and this concept should be formally tested in the setting of a randomised controlled trial.


  1. Vincent JL, et al.: JAMA. 2009, 302: 2323-2329. 10.1001/jama.2009.1754

    Article  CAS  PubMed  Google Scholar 

  2. Chastre J, et al.: Am J Respir Crit Care Med. 2002, 165: 867-903. 10.1164/ajrccm.165.7.2105078

    Article  PubMed  Google Scholar 

  3. Conway Morris A, et al.: Thorax. 2010, 65: 201-207. 10.1136/thx.2009.122291

    Article  Google Scholar 

  4. Wilkinson TS, et al.: Chest. 2012, 142: 1425-1432. 10.1378/chest.11-3273

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and permissions

About this article

Cite this article

Hellyer, T., Simpson, J. Biomarker-based exclusion of ventilator-associated pneumonia: a multicentre validation study. Crit Care 18 (Suppl 1), P303 (2014).

Download citation

  • Published:

  • DOI: