Clinical and hemostatic responses to treatment in ventilator-associated pneumonia: Role of bacterial pathogens

Objective. To determine pathogen-specific kinetic changes in the alveolar procoagulant (PC) activity, tissue factor (TF), and tissue factor pathway inhibitor (TFPI) expression during the course of ventilator-associated pneumonia (VAP) and to assess the relationship between clinical resolution, intral-alveolar bacterial eradication, and restoration of hemostatic balance. Design: Prospective, multiple-center study in a cohort of VAP patients. Setting. Two university-affiliated intensive care units. Patients. Thirty-five patients with microbiologically documented VAP who received adequate antimicrobial coverage and 13 controls. Interventions. Nonbronchoscopic bronchoalveolar lavage was performed at the onset of VAP and on days 4 and 8 after initiation of antibiotic therapy. Samples were assayed for PC, TF, TFPI, and thrombin-antithrombin complex (TATc). The corresponding Clinical Pulmonary Infection Score (CPIS) was collected simultaneously. Measurements and Main Results: Isolated pathogens included Pseudomonas aeruginosa (n = 13), methicillin-resistant Staphylococcus aureus (MRSA) (n = 8), methicillin-sensitive S. aureus (MSSA) (n = 7), and Escherichia coli (n = 7). Although PC activity and TF were increased among the various pathogens at the onset of VAP, the levels of those with P. aeruginosa remained elevated at the end of treatment compared with controls and other etiological agents. TFPI levels were elevated for the duration of the study for all pathogens. A universal increase in TATc was noted at the onset of VAP, but the difference among the group of pathogens was significant at days 4 and 8 posttherapy. Despite the persisting hemostatic imbalance and incomplete intra-alveolar eradication of P. aeruginosa at end of therapy, the CPIS fell comparably at each time point irrespective of the etiological agents. Conclusions: Alveolar activation of the TF-dependent pathway may be species-specific in VAP and may not be adequately balanced by TFPI. The disparity between clinical response and eradication of A aeruginosa from the intra-alveolar space suggests the need for biological markers to guide response to therapy.