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