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.
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.