PURPOSE: Ventilator associated pneumonia (VAP) remains a significant cause of morbidity and mortality in critically ill patients. Until recently, vancomycin remained the only available treatment option for VAP due to methicillin resistant Staphylococcus aureus (MRSA). A pooled analysis of two trials exploring the role of linezolid in the treatment of VAP revealed that the use of linezolid increased significantly the likelihood of cure and improved mortality compared to vancomycin. Recently, elevated plasminogen activator inhibitor-1 (PAI-1) levels were linked to poor outcome. The objective of this study is to determine the impact of antimicrobial therapy on the restoration of homeostatic balance following the use of linezolid versus vancomycin.
METHODS: A total of 16 patients with VAP due to MRSA and four controls were recruited from the critical care units at the Erie County Medical Center in a prospective, open label, randomized 1:1 study of linezolid versus vancomycin. Baseline assessments included medical history, vital signs, chest x-ray, CPIS score, and APACHE II score. A bronchoalveolar lavage was performed at VAP onset and at 72 hours post initiation of therapy. PAI-1 expression and alveolar concentrations were assessed and compared between the linezolid and the vancomycin groups at each time point.
RESULTS: PAI-1 mRNA was significantly elevated at VAP onset compared to controls. Patients in both treatment groups had similar intensity of PAI-1 expression which declined significantly after 72 hours of treatment with either vancomycin or linezolid. There was no difference between the PAI-1 expression and the PAI-1 antigen levels between both groups at each time point.
CONCLUSION: Linezolid is equivalent to vancomycin in reducing the PAI-1 expression in patients with VAP at 72 hours following antibiotic therapy.
CLINICAL IMPLICATIONS: Linezolid is equally effective in reducing the alteration in hemostatic balance in VAP compared to vancomycin.
DISCLOSURE: Ahmad Alhajhusain, Grant monies (from industry related sources) Study was supported by a grant from Pfizer, Inc.; No Product/Research Disclosure Information