Faculty Collaboration Database

Staphylococcus aureus α-Toxin Response Distinguishes Respiratory Virus-Methicillin-Resistant S. aureus Coinfection in Children. J Infect Dis 2016 Dec 01;214(11):1638-1646

Date

09/22/2016

Pubmed ID

27651418

Pubmed Central ID

PMC5144732

DOI

10.1093/infdis/jiw441

Scopus ID

2-s2.0-85014660072 (requires institutional sign-in at Scopus site)   17 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 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.

Author List

Yu KO, Randolph AG, Agan AA, Yip WK, Truemper EJ, Weiss SL, Ackerman KG, Schwarz AJ, Giuliano JS Jr, Hall MW, Bubeck Wardenburg J, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) PICFlu Study Group, PALISI PICFlu Study Group

Author

Rainer G. Gedeit MD Associate Chief Medical Officer in the Children's Administration department at Children's Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Animal Experimentation
Animals
Antibodies, Bacterial
Bacterial Toxins
Child
Child, Preschool
Coinfection
Female
Hemolysin Proteins
Humans
Influenza, Human
Intensive Care Units
Male
Methicillin Resistance
Mice
Neutralization Tests
North America
Respiratory Insufficiency
Staphylococcal Infections
Staphylococcus aureus
Survival Analysis