917. Effect of Linezolid on Pulmonary Cytokines in a Murine Model of Post-influenza Methicilicn Resistant S.aureus (MRSA) Infection
Session: Poster Abstract Session: Bacterial Pathogenesis
Saturday, October 22, 2011
Room: Poster Hall B1

Background: Necrotizing pneumonia caused MRSA following influenza infection is associated with high mortality despite treatment with antibiotics.  Cytokines are postulated to play a major role in pathophysiology and outcome. Linezolid (L) has been shown superior to vancomycin (V) in clinical trials of MRSA pneumonia. We examined the effect of L on pulmonary cytokines in a murine model of postinfluenza MRSA infection.

Methods: On Day (D) 0, C57BL6 mice were infected intranasally (IN) with 1000 PFU Influenza A WSN strain. On D3, 9x10^6 CFU of MRSA (ATCC43300) was given IN. L (100mg/Kg, q12h), and V (180mg/Kg, q12h) were given subcutaneously. Bacterial and vial titers and cytokines were measured in lung homogenates at 4 and 24 hours after antibiotic treatment. Three groups of mice [untreated (C), L and V]were compared using ANOVA with Bonferroni (All-Pairwise) multiple comparison test.

Results: Bacterial titers were 1 log lower in L and V compared to C at 4 and 24 h. Viral titers were similar in the 3 groups of mice at 24 h.  At 4 hours, L and V had lowered IL-6, mKC(human IL-8), IFN-γ and, IL-10 compared to C.   At 24 hours, L and V had lowered IFN-γ and IL-10 compared to C. There was no difference in change of cytokines above between L and V.  In contract IL-1b was lower only in L compared to C (figure, * p<0.05).

Conclusion:  1) MRSA CFU in the lung were decreased similarly by L and V at 4 and 24 hours. 2) Treatment with L or V reduced pulmonary IL-6, mKC and IL-10 at 4 hours and IFN- γ and IL-10 at 24 hours compared to no treatment. There was no difference across the 2 treatment groups. 3) Only mice treated with Linezolid had lower IL1b at 24 hours compared to Control mice.  4) The decrease in pulmonary IL-1b by Linezolid may contribute to the clinical superiority of Linezolid in the treatment of MRSA pneumonia and merits further study.


Subject Category: B. Bacterial pathogenesis, studies in animal models, molecular pathogenicity

Yaling He, MD1, Xinyan Liu, MD, PhD1, Dahlene Fusco, MD, PhD2 and Genovefa Papanicolaou, MD1, (1)Infectious Diseases, Memorial Sloan-Kettering Cancer Center, New York, NY, (2)Massachusetts General Hospital , Boston, MA

Disclosures:

Y. He, None

X. Liu, None

D. Fusco, None

G. Papanicolaou, Pfizer: Grant Investigator, Research grant

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.