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Subcutaneous Infection of Methicillin Resistant Staphylococcus Aureus MRSA
Published on: February 9, 2011
Staphylococcus aureus α-Toxin Response Distinguishes Respiratory Virus-Methicillin-Resistant S. aureus Coinfection in
Karl O A Yu1, Adrienne G Randolph2,3, Anna A Agan2,3
1Department of Pediatrics.
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.
Insights
Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in children with viral infections is deadly. This study shows that MRSA
Area of Science:
- Pediatric Infectious Diseases
- Microbiology
- Immunology
Background:
- Pediatric pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) following viral infections has a high mortality rate.
- Staphylococcus aureus alpha-toxin contributes to lung injury and mortality in mouse models, but its role in pediatric viral-bacterial coinfections remains unclear.
Purpose of the Study:
- To investigate the role of Staphylococcus aureus alpha-toxin in pediatric patients with coinfection of MRSA and influenza virus.
Main Methods:
- Children with acute respiratory failure and suspected influenza were enrolled from 34 North American pediatric intensive care units.
- Serum antibody titers and alpha-toxin neutralization capacity were measured in children with MRSA or methicillin-susceptible S. aureus (MSSA) coinfection and influenza-only controls.
- MRSA isolates were assessed for alpha-toxin production and lethality in a murine pneumonia model.
Main Results:
- Influenza virus was detected in most MRSA coinfection cases (22/25), which had a high mortality rate (9 deaths).
- Children with MSSA coinfection (22 patients) survived.
- MRSA-coinfected patients showed increased anti-alpha-toxin antibody titers and neutralization capacity over time, which correlated with mortality in mice.
Conclusions:
- Alpha-toxin is implicated as a key factor in severe pediatric MRSA pneumonia following viral infections.
- These findings suggest that therapies targeting alpha-toxin neutralization may be beneficial.
