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J Infect Dis. 2016 Dec 1;214(11):1638-1646. Epub 2016 Sep 20.

Staphylococcus aureus α-Toxin Response Distinguishes Respiratory Virus-Methicillin-Resistant S. aureus Coinfection in Children.

Author information

1
Department of Pediatrics.
2
Department of Anesthesia, Perioperative, and Pain Medicine, Boston Children's Hospital.
3
Departments of Anaesthesia and Pediatrics, Harvard Medical School.
4
Department of Biostatistics, Harvard T. H. Chan School of Public Health.
5
Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, Massachusetts.
6
Department of Pediatrics, Children's Hospital of Nebraska, Omaha.
7
Department of Pediatrics, Children's Hospital of Philadelphia, Pennsylvania.
8
Department of Pediatrics, Golisano Children's Hospital, Rochester, New York.
9
Department of Pediatrics, Children's Hospital of Orange County, California.
10
Department of Pediatrics, Yale-New Haven Children's Hospital, Connecticut.
11
Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio.
12
Department of Microbiology, University of Chicago, Illinois.

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 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-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.

RESULTS:

 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.

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.

KEYWORDS:

bacteria; influenza; intensive care unit; pediatric; pneumonia; respiratory failure

PMID:
27651418
PMCID:
PMC5144732
DOI:
10.1093/infdis/jiw441
[Indexed for MEDLINE]
Free PMC Article

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