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.
El-Solh
Ali A
AA
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
Okada
Mifue
M
Pietrantoni
Celestino
C
Aquilina
Alan
A
Berbary
Eileen
E
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