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- Title
Staphylococcus aureus α-Toxin Response Distinguishes Respiratory Virus-Methicillin-Resistant S. aureus Coinfection in Children.
- Authors
Yu, Karl O. A.; Randolph, Adrienne G.; Agan, Anna A.; Wai-Ki Yip; Truemper, Edward J.; Weiss, Scott L.; Ackerman, Kate G.; Schwarz, Adam J.; Giuliano Jr, John S.; Hall, Mark W.; Wardenburg, Juliane Bubeck; Yip, Wai-Ki; Giuliano, John S Jr; Bubeck Wardenburg, Juliane; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) PICFlu Study Group; PALISI PICFlu Study Group
- Abstract
<bold>Background: </bold> 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 coinfection is unclear.<bold>Methods: </bold> We enrolled children across 34 North American pediatric intensive care units with acute respiratory failure and suspected influenza virus infection. Serial serum anti-α-toxin antibody titers and functional α-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 α-toxin production and lethality in a murine pneumonia model.<bold>Results: </bold> Influenza virus was identified in 22 of 25 children with MRSA coinfection (9 died) and 22 patients with MSSA coinfection (all survived). Initial α-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-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.<bold>Conclusions: </bold> 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.
- Subjects
NORTH America; STAPHYLOCOCCUS aureus; RESPIRATORY insufficiency; PEDIATRIC respiratory diseases; INFLUENZA; PNEUMONIA; INTENSIVE care units; INFLUENZA complications; ANIMAL experimentation; BACTERIAL toxins; METHICILLIN resistance; MICE; PROTEINS; RESEARCH funding; STAPHYLOCOCCAL diseases; SURVIVAL analysis (Biometry); BACTERIAL antibodies; NEUTRALIZATION tests; MIXED infections; DISEASE complications
- Publication
Journal of Infectious Diseases, 2016, Vol 214, Issue 11, p1638
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiw441