title: Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia.
abstract: BACKGROUND
  Post influenza pneumonia is a leading cause of mortality and morbidity, with mortality rates approaching 60% when bacterial infections are secondary to multi-drug resistant (MDR) pathogens. Staphylococcus aureus, in particular community acquired MRSA (cMRSA), has emerged as a leading cause of post influenza pneumonia.
  
  
  OBJECTIVE
  Linezolid (LZD) prevents acute lung injury in murine model of post influenza bacterial pneumonia.
  
  
  METHODS
  Mice were infected with HINI strain of influenza and then challenged with cMRSA at day 7, treated with antibiotics (LZD or Vanco) or vehicle 6 hours post bacterial challenge and lungs and bronchoalveolar lavage fluid (BAL) harvested at 24 hours for bacterial clearance, inflammatory cell influx, cytokine/chemokine analysis and assessment of lung injury.
  
  
  RESULTS
  Mice treated with LZD or Vanco had lower bacterial burden in the lung and no systemic dissemination, as compared to the control (no antibiotic) group at 24 hours post bacterial challenge. As compared to animals receiving Vanco, LZD group had significantly lower numbers of neutrophils in the BAL (9×10(3) vs. 2.3×10(4), p < 0.01), which was associated with reduced levels of chemotactic chemokines and inflammatory cytokines KC, MIP-2, IFN-γ, TNF-α and IL-1β in the BAL. Interestingly, LZD treatment also protected mice from lung injury, as assessed by albumin concentration in the BAL post treatment with H1N1 and cMRSA when compared to vanco treatment. Moreover, treatment with LZD was associated with significantly lower levels of PVL toxin in lungs.
  
  
  CONCLUSIONS
  Linezolid has unique immunomodulatory effects on host inflammatory response and lung injury in a murine model of post-viral cMRSA pneumonia.
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors: Urvashi
authors: U
authors: Bhan
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors: Amy B
authors: AB
authors: Podsiad
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors: Melissa A
authors: MA
authors: Kovach
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Ohio State University, Columbus, Ohio, United States of America.
authors: Megan N
authors: MN
authors: Ballinger
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors: Venkateshwar
authors: V
authors: Keshamouni
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors: Theodore J
authors: TJ
authors: Standiford
mesh_terms: D000081:Acetamides / Q000008:administration & dosage*; D000818:Animals; D006801:Humans; D056747:Immunomodulation; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000472:pathogenicity; D007251:Influenza, Human / Q000150:complications / Q000188:drug therapy*; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity; D051379:Mice; D023303:Oxazolidinones / Q000008:administration & dosage*; D018410:Pneumonia, Bacterial / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy
chemical_list: D000081:Acetamides; D023303:Oxazolidinones; D000069349:Linezolid
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