Changes in Pulmonary Cytokines during Antibiotic Therapy for Ventilator-Associated Pneumonia

Background: A major unanswered question in ventilator-associated pneumonia (VAP) management relates to patient response to therapy. We investigated the use of pulmonary cytokines as biomarkers for response to antibiotic therapy for VAP. Methods: Prospective, observational pilot study of 12 critically ill trauma patients with VAP using a bronchoscopic bronchoalveolar lavage (BAL) (>= 100,000 colony-forming units [cfu]/mL). All patients underwent repeat BAL after three days of adequate antibiotic therapy. Changes in pulmonary effluent interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha concentrations measured on diagnostic and repeat BAL were evaluated on the basis of the presence of a microbiologic response (<10,000 cfu/mL on repeat BAL). Results: Six post-therapy BAL samples showed a microbiologic response. In responders, IL-8 and TNF-alpha concentrations decreased significantly (1,303 +/- 1,150 ng/mL in diagnostic BAL sample vs. 309 +/- 448 ng/mL after response; p = 0.08 and 9.9 +/- 18.4 ng/mL in diagnostic vs. 0.1 +/- 0.1 ng/mL in post-treatment sample; p = 0.06, respectively). In non-responders, IL-8 (449 +/- 426 ng/mL vs. 326 +/- 319 ng/mL; p = 0.59) and TNF-alpha (1.2 +/- 1.9 ng/mL vs. 0.3 +/- 0.3 ng/mL; p = 0.31) did not change significantly. Clinical response measures did not change or increased in responders, whereas these parameters did not change or decreased paradoxically in non-responders. Conclusion: This pilot study indicates pulmonary concentrations of IL-8 and TNF-alpha decrease in microbiologic responders with VAP. Conversely, clinical response parameters were discordant with the microbiologic response. The utility of pulmonary cytokine behavior in evaluating the effectiveness of antibiotic therapy for VAP should be studied further.