PURPOSE: Bacterial pneumonia is a well described complication of influenza. In recent years, community-onset methicillin-resistant Staphylococcus aureus (cMRSA) infection has emerged as a contributor to morbidity and mortality in patients with influenza. Linezolid (LZD) is an oxazolidinone, the first new class of antibiotic developed in the last three decades. Although it is predominantly bacteriostatic, linezolid exhibits effective in-vitro and in-vivo activity against a wide variety of Gram-positive organisms, including methicillin susceptible S. aureus and methicillin-resistant S.aureus (MRSA). In this study we wanted to assess the effect of Linezolid on lung inflammatory response as well as lung injury in a murine model of post viral bacterial pneumonia as compared to Vancomycin (Vanco).
METHODS: Mice were infected with HINI strain of influenza and then challenged with cMRSA at day 7, treated with Abx at 6 hours and lungs harvested at 24 hours for bacterial clearance, inflammatory cell influx, cytokine/chemokines analysis and evidence of lung injury.
RESULTS: Mice treated with LZD or Vanco had significantly lower bacterial CFU in the lung with no systemic dissemination at 24 hours, though as compared to Vanco, mice treated with LZD had significantly lower number of neutrophils in the BAL (9x103 vs 2.3x104, p< 0.01) as compared to Vanco treated group. This was associated with significantly lower levels of proinflammatory cytokine TNF-α as well as chemokines KC, KE and IP-10. Interestingly, mice treated with LZD were protected from acute lung injury as measured by albumin leak in the BAL as compared to the Vanco treated group.
CONCLUSIONS: In conclusion, our study suggests that Linezolid has unique immunomodulatory effects on host inflammatory response and lung injury in a murine model of post-viral cMRSA pneumonia
CLINICAL IMPLICATIONS: LZD has immunomodulatory effects and protects against acute lung injury in post viral bacterial pneumonia
DISCLOSURE: Urvashi Bhan: University grant monies: ASPIRE grant
The following authors have nothing to disclose: Carol Wilke, Megan Ballinger, Theodore Standiford
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