Effect of linezolid on clinical severity and pulmonary cytokines in a murine model of influenza A and Staphylococcus aureus coinfection.

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.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.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