Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia

Thomas P Hellyer, Andrew Conway Morris, Daniel F. McAuley, Timothy S Walsh, Niall H Anderson, Suveer Singh, Paul Dark, Alistair I Roy, Simon V Baudouin, Stephen E Wright, Gavin D. Perkins, Kallirroi Kefala, Melinda Jeffels, Ronan McMullan, Cecilia M. O'Kane, Craig Spencer, Shondipon Laha, Nicole Robin, Savita Gossain, Kate GouldMarie-Hélène Ruchaud-Sparagano, Jonathan Scott, Emma M Browne, James G MacFarlane, Sarah Wiscombe, John D Widdrington, Ian Dimmick, Ian F Laurenson, Frans Nauwelaers, A. John Simpson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)
193 Downloads (Pure)


Background: Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare.

Objectives: We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP. 

Methods: A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >104 colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1β), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination. 

Results: Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (p<0.001). The area under the receiver operator characteristic curve for IL-1β was 0.81; IL-8, 0.74; MMP-8, 0.76; MMP-9, 0.79 and HNE, 0.78. A combination of IL-1β and IL-8, at the optimal cut-point, excluded VAP with a sensitivity of 100%, a specificity of 44.3% and a post-test probability of 0% (95% CI 0% to 9.2%). 

Conclusions: Low BALF IL-1β in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.

Original languageEnglish
Pages (from-to)41-47
Number of pages7
Issue number1
Early online date08 Oct 2014
Publication statusPublished - Jan 2015

Bibliographical note

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
This manuscript describes a multicentre trial of a new diagnostic test for detecting pneumonia in ICU patients, for which I was lead microbiologist in a national consortium of trialists. With 28 citations, to date, this reflects impact on the body of evidence on the topic, with an average of almost 6 citations per year since publication.


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