title: Effect of linezolid on clinical severity and pulmonary cytokines in a murine model of influenza A and Staphylococcus aureus coinfection.
abstract: Excessive inflammation contributes to the severity of post influenza pneumonia caused by methicillin resistant S.aureus (MRSA). Linezolid, vancomycin, and clindamycin are antibiotics used for MRSA infections. Linezolid has immunomodulatory properties. We report on the effects of the three antibiotics on microbial clearance, pulmonary cytokines and clinical course in a murine model of influenza and MRSA coinfection.
  
  
  METHODS
  B6 mice were infected with influenza A virus and 3 days later with MRSA, both intranasally. Treatment with placebo, linezolid, vancomycin or clindamycin started immediately after MRSA infection and continued for 72 hours. Bacterial and viral titers as well as cytokine concentrations in the lungs were assessed 4 and 24 hours after MRSA coinfection. Mice were weighted daily for 13 days.
  
  
  RESULTS
  Coinfected mice had increased pulmonary IL-1β, TNF-α and mKC at 4 and 24 hours, IL-6, IL-10 and IL-12 at 4 hours and IFN-γ at 24 hours after MRSA coinfection (all P<0.05). Compared to placebo, coinfected mice treated with linezolid, vancomycin or clindamycin had decreased pulmonary IL-6 and mKC at 4 hours and IFN-γ at 24 hours after MRSA coinfection (all P<0.05). IL-1β, TNF-α and IL-12 were similar in antibiotic-treated and placebo groups. All antibiotics similarly reduced MRSA without effect on influenza titers. Linezolid-treated mice had less weight loss on days 4-6 after influenza infection compared to placebo (all P<0.05). On all other days weight change was similar among all groups.
  
  
  CONCLUSIONS
  This is the first report comparing the effects of antibiotics on cytokines and clinical outcome in a murine model of influenza and MRSA coinfection. Compared to placebo, antibiotic treatment reduced maximum concentration of IL-6, mKC and IFN-γ in the lungs without any difference among antibiotics. During treatment, only linezolid delayed weight loss compared to placebo.
authors.affiliation: Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Liu
authors.forename: Yaling
authors.initials: Y
authors.lastname: He
authors.forename: Kun
authors.initials: K
authors.lastname: Xiao
authors.forename: Julie R
authors.initials: JR
authors.lastname: White
authors.forename: Dahlene N
authors.initials: DN
authors.lastname: Fusco
authors.forename: Genovefa A
authors.initials: GA
authors.lastname: Papanicolaou
mesh_terms: D000081:Acetamides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D058491:Bacterial Load; D060085:Coinfection; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D000069349:Linezolid; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D023303:Oxazolidinones / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load; D015431:Weight Loss
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D007155:Immunologic Factors; D007378:Interleukins; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid