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

Lookup NU author(s): Thomas Hellyer, Dr Simon Baudouin, Dr Stephen Wright, Melinda Jeffels, Dr Marie Ruchaud-Sparagano, Dr Emma Browne, Dr Jim Macfarlane, Dr Sarah Wiscombe, Dr John Widdrington, Ian Dimmick, Professor John Simpson

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Abstract

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 >10(4) colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1 beta), 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-1 beta was 0.81; IL-8, 0.74; MMP8, 0.76; MMP-9, 0.79 and HNE, 0.78. A combination of IL-1 beta 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-1 beta 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.


Publication metadata

Author(s): Hellyer TP, Morris AC, McAuley DF, Walsh TS, Anderson NH, Singh S, Dark P, Roy AI, Baudouin SV, Wright SE, Perkins GD, Kefala K, Jeffels M, McMullan R, O'Kane CM, Spencer C, Laha S, Robin N, Gossain S, Gould K, Ruchaud-Sparagano MH, Scott J, Browne EM, MacFarlane JG, Wiscombe S, Widdrington JD, Dimmick I, Laurenson IF, Nauwelaers F, Simpson AJ

Publication type: Article

Publication status: Published

Journal: Thorax

Year: 2015

Volume: 70

Issue: 1

Pages: 41-47

Print publication date: 01/01/2015

Online publication date: 08/10/2014

Acceptance date: 07/09/2014

ISSN (print): 0040-6376

ISSN (electronic): 1468-3296

Publisher: BMJ Publishing Group

URL: http://dx.doi.org/10.1136/thoraxjnl-2014-205766

DOI: 10.1136/thoraxjnl-2014-205766


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