Diagnostic importance of pulmonary interleukin-1 beta and interleukin-8 in ventilator-associated pneumonia online first

ABSTRACT
Background
Ventilator-associated pneumonia (VAP) is the most commonly fatal nosocomial infection. Clinical diagnosis of VAP remains notoriously inaccurate. We tested the hypothesis that significantly augmented inflammatory markers distinguish VAP from conditions closely mimicking VAP.

Methods
A prospective, observational cohort study 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/ml 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 (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, 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.