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.


METHODS
Descriptive observational study in a 12-bed medical intensive care unit in a university-affiliated hospital.


METHODS
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 PaO(2)/FIO(2). 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.
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, School of Medicine and Biomedical Sciences, Erie County Medical Center, University at Buffalo, Buffalo, NY 14215 , USA. solh@buffalo.edu
Ali A
AA
El-Solh
Mifue
M
Okada
Celestino
C
Pietrantoni
Alan
A
Aquilina
Eileen
E
Berbary
D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D003428:Cross Infection / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D004363:Drug Utilization / Q000592:standards*; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D011014:Pneumonia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome; D012122:Ventilators, Mechanical / Q000009:adverse effects* / Q000382:microbiology
D000900:Anti-Bacterial Agents