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Effect of linezolid on clinical severity and pulmonary cytokines in a murine model of influenza A and Staphylococcus aureus coinfection.
PLoS One 2013; 8(3):e57483Plos

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+Show Affiliations

Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23478252

Citation

Liu, Xinyan, et al. "Effect of Linezolid On Clinical Severity and Pulmonary Cytokines in a Murine Model of Influenza a and Staphylococcus Aureus Coinfection." PloS One, vol. 8, no. 3, 2013, pp. e57483.
Liu X, He Y, Xiao K, et al. Effect of linezolid on clinical severity and pulmonary cytokines in a murine model of influenza A and Staphylococcus aureus coinfection. PLoS ONE. 2013;8(3):e57483.
Liu, X., He, Y., Xiao, K., White, J. R., Fusco, D. N., & Papanicolaou, G. A. (2013). Effect of linezolid on clinical severity and pulmonary cytokines in a murine model of influenza A and Staphylococcus aureus coinfection. PloS One, 8(3), pp. e57483. doi:10.1371/journal.pone.0057483.
Liu X, et al. Effect of Linezolid On Clinical Severity and Pulmonary Cytokines in a Murine Model of Influenza a and Staphylococcus Aureus Coinfection. PLoS ONE. 2013;8(3):e57483. PubMed PMID: 23478252.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of linezolid on clinical severity and pulmonary cytokines in a murine model of influenza A and Staphylococcus aureus coinfection. AU - Liu,Xinyan, AU - He,Yaling, AU - Xiao,Kun, AU - White,Julie R, AU - Fusco,Dahlene N, AU - Papanicolaou,Genovefa A, Y1 - 2013/03/05/ PY - 2012/05/30/received PY - 2013/01/24/accepted PY - 2013/3/13/entrez PY - 2013/3/13/pubmed PY - 2013/8/21/medline SP - e57483 EP - e57483 JF - PloS one JO - PLoS ONE VL - 8 IS - 3 N2 - UNLABELLED: 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23478252/Effect_of_linezolid_on_clinical_severity_and_pulmonary_cytokines_in_a_murine_model_of_influenza_A_and_Staphylococcus_aureus_coinfection_ L2 - http://dx.plos.org/10.1371/journal.pone.0057483 DB - PRIME DP - Unbound Medicine ER -