Procoagulant and fibrinolytic activity in ventilator-associated pneumonia: impact of inadequate antimicrobial therapy

Objective: To determine the homeostatic balance of patients with ventilator-associated pneumonia (VAP) with respect to the adequacy of antimicrobial therapy. Design and setting: Descriptive observational study in a 12-bed medical intensive care unit in a university-affiliated hospital. Patients: Twenty-nine patients with VAP documented by quantitative culture of bronchoalveolar secretions and a control group of eight mechanically ventilated patients. Methods: Serial bronchoalveolar lavage fluid (BALF) samples were assayed for prothrombin activation fragment (F1+2), thrombin-antithrombin (TAT) complex, fibrinolytic activity, urokinase-type plasminogen activator (u-PA), and plasminogen activator inhibitor type 1 (PAI-1) on days 1, 4, and 7 after VAP onset. Results: Pathogens isolated from patients with inadequate empirical antimicrobial coverage included methicillin-resistant Staphylococcus aureus (n=2), Pseudomonas aeruginosa (n=4), and Acinetobacter baumannii (n=1). Compared to those who received adequate antibiotic therapy, TAT, F1+2, and PAI-1 levels increased while u-PA levels remained unchanged. Despite antibiotic adjustment on day 4, TAT levels remained elevated in those who lacked adequate antimicrobial coverage and were significantly correlated with PaO2/FIO2. The procoagulant activity was accompanied by a local depression of fibrinolytic capacity that was attributed mainly to increased BALF PAI-1 levels. Nonsurvivors showed significantly higher levels of TAT and PAI-1 than survivors. No significant correlation between the bacterial burden and the homeostatic derangements was documented. Conclusions: The lung inflammatory response seems to promulgate a local procoagulant activity associated with hypoxemia in those with inadequate antibiotic therapy. The homeostatic derangement seems to be independent of the lung bacterial burden.