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Staphylococcus aureus α-toxin Response Distinguishes Respiratory Virus-MRSA Co-infection in Children

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  • Staphylococcus aureus α-toxin Response Distinguishes Respiratory Virus-MRSA Co-infection in Children

    J Infect Dis. 2016 Sep 20. pii: jiw441. [Epub ahead of print]
    Staphylococcus aureus α-toxin Response Distinguishes Respiratory Virus-MRSA Co-infection in Children.

    Yu KO, Randolph AG, Agan AA, Yip WK, Truemper E, Weiss S, Ackerman K, Schwarz A, Guiliani J, Hall MW, Bubeck Wardenburg J; PALISI PICFlu Study Group.
    Collaborators (99)

    Abstract

    BACKGROUND:

      Development of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia after a respiratory viral infection is frequently fatal in children. In mice, S. aureus α-toxin directly injures pneumocytes and increases mortality, whereas α-toxin blockade mitigates disease. The role of α-toxin in pediatric staphylococcal-viral co-infection is unclear.
    METHODS:

     We enrolled children across 34 North American pediatric intensive care units with acute respiratory failure and suspected influenza infection. Serial serum anti-α-toxin antibody titers and functional α-toxin neutralization capacity were compared across children co-infected with MRSA, methicillin-sensitive S. aureus (MSSA), and influenza mono-infected controls. MRSA isolates were tested for α-toxin production and lethality in a murine pneumonia model.
    RESULTS:

     Influenza virus was identified in 22 of 25 children with MRSA co-infection (9 died) and 22 patients with MSSA co-infection (all survived). Initial α-toxin-specific antibody titers were similar compared to the 13 influenza controls. In patients with serial samples, only MRSA co-infected patients showed time-dependent increases in anti-α-toxin titer and functional neutralization capacity. MRSA α-toxin production from patient isolates correlated with initial serologic titers, and with mortality in murine pneumonia.
    CONCLUSIONS:

      These data implicate α-toxin as a relevant antigen in severe pediatric MRSA pneumonia associated with respiratory viral infection, supporting a potential role for toxin-neutralizing therapy.
    ? The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.


    PMID: 27651418 DOI: 10.1093/infdis/jiw441
    [PubMed - as supplied by publisher]
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