Staphylococcus aureus a-toxin response distinguishes respiratory virus-methicillin-resistant s. aureus coinfection in children

Karl O.A. Yu, Adrienne G. Randolph, Anna A. Agan, Wai Ki Yip, Edward J. Truemper, Scott L. Weiss, Kate G. Ackerman, Adam J. Schwarz, John S. Giuliano, Mark W. Hall, Juliane Bubeck Wardenburg

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9 Scopus citations

Abstract

Background. Development of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia after a respiratory viral infection is frequently fatal in children. In mice, S. aureus a-toxin directly injures pneumocytes and increases mortality, whereas a-toxin blockade mitigates disease. The role of a-toxin in pediatric staphylococcal-viral coinfection is unclear. Methods. We enrolled children across 34 North American pediatric intensive care units with acute respiratory failure and suspected influenza virus infection. Serial serum anti-a-toxin antibody titers and functional a-toxin neutralization capacity were compared across children coinfected with MRSA or methicillin-susceptible S. aureus (MSSA) and control children infected with influenza virus only. MRSA isolates were tested for a-toxin production and lethality in a murine pneumonia model. Results. Influenza virus was identified in 22 of 25 children with MRSA coinfection (9 died) and 22 patients with MSSA coinfection (all survived). Initial a-toxin-specific antibody titers were similar, compared with those in the 13 controls. In patients with serial samples, only MRSA-coinfected patients showed time-dependent increases in anti-a-toxin titer and functional neutralization capacity. MRSA a-toxin production from patient isolates correlated with initial serologic titers and with mortality in murine pneumonia. Conclusions. These data implicate a-toxin as a relevant antigen in severe pediatric MRSA pneumonia associated with respiratory viral infection, supporting a potential role for toxin-neutralizing therapy.

Original languageEnglish
Pages (from-to)1638-1646
Number of pages9
JournalJournal of Infectious Diseases
Volume214
Issue number11
DOIs
StatePublished - Jan 1 2016

Keywords

  • Bacteria
  • Influenza
  • Intensive care unit
  • Pediatric
  • Pneumonia
  • Respiratory failure

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    Yu, K. O. A., Randolph, A. G., Agan, A. A., Yip, W. K., Truemper, E. J., Weiss, S. L., Ackerman, K. G., Schwarz, A. J., Giuliano, J. S., Hall, M. W., & Wardenburg, J. B. (2016). Staphylococcus aureus a-toxin response distinguishes respiratory virus-methicillin-resistant s. aureus coinfection in children. Journal of Infectious Diseases, 214(11), 1638-1646. https://doi.org/10.1093/infdis/jiw441