• 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 Gould, Marie-Hélène Ruchaud-Sparagano, Jonathan Scott, Emma M Browne, James G MacFarlane, Sarah Wiscombe, John D Widdrington, Ian Dimmick, Ian F Laurenson, Frans Nauwelaers, and A John Simpson.
• Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK.
• Thorax. 2015 Jan 1;70(1):41-7.

BackgroundExcessive 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.ObjectivesWe sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP.MethodsA 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 >10(4) 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.ResultsPaired 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%).ConclusionsLow 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.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.

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