Validation of the riboleukogram to detect ventilator-associated pneumonia after severe injury.

Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in the critically ill, occurring in 10% to 20% of those patients receiving mechanical ventilation.1 The rate of VAP is highest in trauma patients and is independently associated with death in those that are less severely injured.2,3 Because VAP also increases days on the ventilator, the resulting increase in trauma-associated costs is substantial, as high as $57,000 per episode.4 These significant increases in morbidity, mortality, and cost have made lowering VAP rates an obvious target for quality care. Recent reports indicate that preventative measures are effective in significantly decreasing the rates of VAP after injury, sparking interest in VAP as a metric for performance improvement.5–7 Improvements in the treatment of VAP, however, are confounded by the absence of accurate and timely diagnostics. Without a “gold standard,” the diagnostic criteria for VAP remain controversial, as it is difficult to distinguish VAP from tracheal colonization in patients with other forms of lung injury.6,8,9 Thus, “the establishment of an appropriate diagnosis of VAP is one of the most crucial and difficult issues in the care of critically ill patients.”10 There is a tendency for clinicians to over diagnose VAP, because of the dire consequences of untreated or inappropriately treated pneumonia.6,9,11,12 This practice not only risks the harm of unnecessary antibiotics, but also increases the likelihood of infection with resistant organisms.9 Advances in molecular diagnostics thus hold great promise for VAP, especially if these tests could determine earlier the offending organism(s). Recent reports suggested the clinical utility of riboleukograms, that is, circulating leukocyte transcriptional profiles over time, used to track the host response to and recovery from critical illness complicated by pneumonia.13,14 On the basis of the report of an 85-gene riboleukogram,13 coupled with our own preclinical data,15–17 we hypothesized that gene expression analysis could be used to classify host responses to severe injury complicated by VAP. We tested this hypothesis using data from an existing cohort of 158 intubated trauma patients to validate the ability of these 85 genes to detect VAP and to predict its occurrence days previous to the clinical diagnosis. The patient data are housed in a Trauma-related Database (TRDB)18 created by the Inflammation and Host Response to Injury Program (Trauma Glue Grant),19 a 10-year, large-scale collaborative research program funded by the National Institute of General Medical Sciences. Sample collection and processing protocols had been developed in a series of experiments that sought to validate the informational value of changes in the relative abundance of mRNA in circulating leukocytes.20,21