title: Staphylococcus aureus α-Toxin Response Distinguishes Respiratory Virus-Methicillin-Resistant S. aureus Coinfection in Children.
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.
authors.affiliation: Department of Pediatrics.
authors.forename: Karl O A
authors.initials: KO
authors.lastname: Yu
authors.affiliation: Department of Anesthesia, Perioperative, and Pain Medicine, Boston Children's Hospital.|Departments of Anaesthesia and Pediatrics, Harvard Medical School.
authors.forename: Adrienne G
authors.initials: AG
authors.lastname: Randolph
authors.affiliation: Department of Anesthesia, Perioperative, and Pain Medicine, Boston Children's Hospital.|Departments of Anaesthesia and Pediatrics, Harvard Medical School.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Agan
authors.affiliation: Department of Biostatistics, Harvard T. H. Chan School of Public Health.|Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Wai-Ki
authors.initials: WK
authors.lastname: Yip
authors.affiliation: Department of Pediatrics, Children's Hospital of Nebraska, Omaha.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Truemper
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Pennsylvania.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Weiss
authors.affiliation: Department of Pediatrics, Golisano Children's Hospital, Rochester, New York.
authors.forename: Kate G
authors.initials: KG
authors.lastname: Ackerman
authors.affiliation: Department of Pediatrics, Children's Hospital of Orange County, California.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Schwarz
authors.affiliation: Department of Pediatrics, Yale-New Haven Children's Hospital, Connecticut.
authors.forename: John S
authors.initials: JS
authors.lastname: Giuliano
authors.affiliation: Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Hall
authors.affiliation: Department of Pediatrics.|Department of Microbiology, University of Chicago, Illinois.
authors.forename: Juliane
authors.initials: J
authors.lastname: Bubeck Wardenburg
mesh_terms: D000293:Adolescent; D032761:Animal Experimentation; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001427:Bacterial Toxins / Q000276:immunology* / Q000633:toxicity*; D002648:Child; D002675:Child, Preschool; D060085:Coinfection / Q000150:complications / Q000473:pathology*; D005260:Female; D006460:Hemolysin Proteins / Q000276:immunology* / Q000633:toxicity*; D006801:Humans; D007251:Influenza, Human / Q000150:complications*; D007362:Intensive Care Units; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D009500:Neutralization Tests; D009656:North America; D012131:Respiratory Insufficiency / Q000473:pathology*; D013203:Staphylococcal Infections / Q000150:complications / Q000473:pathology*; D013211:Staphylococcus aureus / Q000145:classification / Q000302:isolation & purification; D016019:Survival Analysis
chemical_list: D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin
keywords: bacteria; influenza; intensive care unit; pediatric; pneumonia; respiratory failure