Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia

Anita J Campbell1, Shakeel Mowlaboccus2, Geoffrey W Coombs3

  • 1Department of Infectious Diseases, Perth Children's Hospital, Perth, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute. Perth, Australia; School of Medicine, University of Western Australia, Perth, Australia.

Insights

Antimicrobial resistance in Staphylococcus aureus (S. aureus) is critical in childhood infections. Panton-Valentine leukocidin (PVL) positivity in S. aureus bacteraemia (SAB) was the sole molecular predictor of poor outcomes in children.

Area of Science:

  • Microbiology and Infectious Diseases
  • Genomics and Molecular Epidemiology
  • Pediatric Infectious Diseases

Background:

  • Staphylococcus aureus antimicrobial resistance (S. aureus) and its toxins are increasingly recognized as significant factors in childhood disease.
  • Understanding the genetic basis of S. aureus virulence is crucial for effective clinical management and improving patient outcomes.
  • The role of methicillin-susceptible S. aureus (MSSA) in healthcare-associated infections requires further investigation.

Purpose of the Study:

  • To explore the role of S. aureus antimicrobial resistance genes and toxins in childhood disease severity and outcomes.
  • To analyze whole genome sequencing (WGS) data alongside clinical information for children hospitalized with S. aureus bacteraemia (SAB).
  • To identify molecular predictors of poor outcomes in pediatric SAB.

Main Methods:

  • A prospective, multisite study involving Australian and New Zealand children hospitalized with SAB between 2017-2018.
  • Whole genome sequencing (WGS) was performed on 353 SAB isolates, paired with clinical data from the ISAIAH cohort.
  • Analysis included identification of sequence types (STs), clonal complexes (CCs), and the presence of Panton-Valentine leukocidin (PVL).

Main Results:

  • Of 353 SAB isolates, 85% were methicillin-susceptible S. aureus (MSSA) and 15% were methicillin-resistant S. aureus (MRSA).
  • MSSA was predominant in healthcare-associated SAB (87%), while PVL-positive SAB occurred in 22% of cases, predominantly MSSA and community-onset.
  • PVL positivity was the only independent microbiological predictor of poor outcomes in community-onset SAB (aOR 2.6).

Conclusions:

  • MSSA plays a significant, previously under-recognized role in harboring genetic virulence and causing healthcare-associated infections in children.
  • PVL positivity emerged as the sole molecular independent predictor of poor outcomes in pediatric SAB.
  • Further research is needed to understand the implications of PVL-producing S. aureus strains on clinical management strategies.
Abstract

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