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Abstract
Background Ventilator-associated pneumonia (VAP) is the most commonly fatal nosocomial infection. Clinical diagnosis of VAP remains notoriously inaccurate. The hypothesis was tested that significantly augmented inflammatory markers distinguish VAP from conditions closely mimicking VAP.
Methods A prospective, observational cohort study was carried out in two university hospital intensive care units recruiting 73 patients with clinically suspected VAP, and a semi-urban primary care practice recruiting a reference group of 21 age- and sex-matched volunteers.
Growth of pathogens at >104 colony-forming units (cfu)/ml of bronchoalveolar lavage fluid (BALF) distinguished VAP from “non-VAP”. Inflammatory mediators were quantified in BALF and serum. Mediators showing significant differences between patients with and without VAP were analysed for diagnostic utility by receiver operator characteristic (ROC) curves.
Results Seventy-two patients had recoverable lavage—24% had VAP. BALF interleukin-1β (IL-1β), IL-8, granulocyte colony-stimulating factor and macrophage inflammatory protein-1α were significantly higher in the VAP group (all p<0.005). Using a cut-off of 10 pg/ml, BALF IL-1β generated negative likelihood ratios for VAP of 0.09. In patients with BALF IL-1β <10 pg/ml the post-test probability of VAP was 2.8%. Using a cut-off value for IL-8 of 2 ng/ml, the positive likelihood ratio was 5.03. There was no difference in cytokine levels between patients with sterile BALF and those with growth of <104 cfu/ml.
Conclusions BALF IL-1β and IL-8 are amongst the strongest markers yet identified for accurately demarcating VAP within the larger population of patients with suspected VAP. These findings have potential implications for reduction in unnecessary antibiotic use but require further validation in larger populations.
- Assisted ventilation
- cytokine biology
- bacterial infection
- bronchoscopy
- pneumonia
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Footnotes
Linked articles 127308.
Funding Sir Jules Thorn Charitable Trust, 24 Manchester Square, London W1U 3TH. DJD is a Wellcome Trust Career Development Fellow (Fellowship # 078265). Other Funders: Wellcome Trust.
Competing interests ACM has received an academic prize (travel and accommodation to attend an international conference) funded by Eli Lily. AJS has received expenses from Astra Zeneca and Glaxo Smith Kline (for travel and accommodation) to attend international educational conferences. IFL has received expenses from Astra Zeneca (for travel and accommodation) to attend international educational conferences. TSW is the recipient of an unrestricted educational grant from Wyeth Pharmaceuticals for work concerning epidemiology of ICU-acquired infection. All other authors have no conflicts of interest to declare
Ethics approval This study was conducted with the approval of the Lothian Research Ethics Committee.
ACM collected and analysed data, drafted the manuscript and approves the final version. KK conceived the study, collected and analysed data, drafted the manuscript and approves the final version. TSW collected and analysed data, reviewed the manuscript and approves the final version. OLMN collected and analysed data, reviewed the manuscript and approves the final version. KD collected and analysed data, reviewed the manuscript and approves the final version. LF collected data, reviewed the manuscript and approves the final version. TSW identified patients, assisted in data collection reviewed the manuscript and approves the final version. SJM identified patients, assisted in data collection reviewed the manuscript and approves the final version. DGS identified patients, assisted in data collection reviewed the manuscript and approves the final version. PJA identified patients, assisted in data collection reviewed the manuscript and approves the final version. NA analysed the data, reviewed the manuscript and approves the final version. JRG collected the data, reviewed the manuscript and approves the final version. IFL collected the data, reviewed the manuscript and approves the final version. HR identified the matched volunteers, reviewed the manuscript and approves the final version. DJD analysed the data, reviewed the manuscript and approves the final version. CH conceived the study, obtained funding, reviewed the manuscript and approves the final version. JMS conceived the study, obtained funding, reviewed the manuscript and approves the final version. AJS conceived the study, obtained funding, collected and analysed the data, drafted the manuscript and approves the final version.
Provenance and peer review Not commissioned; externally peer reviewed.
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