Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia

Anita J Campbell; Shakeel Mowlaboccus; Geoffrey W Coombs; Denise A Daley; Laila S Al Yazidi; Linny K Phuong; Clare Leung; Emma J Best; Rachel H Webb; Lesley Voss; Eugene Athan; Philip N Britton; Penelope A Bryant; Coen T Butters; Jonathan R Carapetis; Natasha S Ching; Joshua Francis; Te-Yu Hung; Clare Nourse; Samar Ojaimi; Alex Tai; Nan Vasilunas; Brendan McMullan; Asha C Bowen; Christopher C Blyth; Australian and New Zealand Pediatric Infectious Diseases (ANZPID) clinical research network (CRN) of the Australasian Society of Infectious Diseases (ASID) and the Australian Group on Antimicrobial Resistance (AGAR)

doi:10.1016/j.jgar.2022.03.012

Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia

J Glob Antimicrob Resist. 2022 Jun:29:197-206. doi: 10.1016/j.jgar.2022.03.012. Epub 2022 Mar 25.

Authors

Anita J Campbell¹, Shakeel Mowlaboccus², Geoffrey W Coombs³, Denise A Daley⁴, Laila S Al Yazidi⁵, Linny K Phuong⁶, Clare Leung⁷, Emma J Best⁸, Rachel H Webb⁹, Lesley Voss¹⁰, Eugene Athan¹¹, Philip N Britton¹², Penelope A Bryant¹³, Coen T Butters⁶, Jonathan R Carapetis¹⁴, Natasha S Ching¹⁵, Joshua Francis¹⁶, Te-Yu Hung¹⁷, Clare Nourse¹⁸, Samar Ojaimi¹⁹, Alex Tai²⁰, Nan Vasilunas²¹, Brendan McMullan²², Asha C Bowen²³, Christopher C Blyth²⁴; Australian and New Zealand Pediatric Infectious Diseases (ANZPID) clinical research network (CRN) of the Australasian Society of Infectious Diseases (ASID) and the Australian Group on Antimicrobial Resistance (AGAR)

Affiliations

¹ Department 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. Electronic address: [email protected].
² College of Science, Health, Engineering and Education, Murdoch University, Murdoch; Department of Microbiology, PathWest Laboratory Medicine WA, Fiona Stanley Hospital, Western Australia; School of Biomedical Sciences, University of Western Australia, Nedlands.
³ College of Science, Health, Engineering and Education, Murdoch University, Murdoch; Department of Microbiology, PathWest Laboratory Medicine WA, Fiona Stanley Hospital, Western Australia.
⁴ Department of Microbiology, PathWest Laboratory Medicine WA, Fiona Stanley Hospital, Western Australia; The Australian Group on Antimicrobial Resistance (AGAR).
⁵ Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman; Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Sydney, Australia; The Children's Department of Infectious Diseases and Microbiology, the Children's Hospital at Westmead, NSW, Australia.
⁶ Department of General Medicine, Infectious Diseases Unit, Royal Children's Hospital, Melbourne, Australia; Infection and Immunity Group, Murdoch Children's Research Institute, Melbourne, Australia.
⁷ Department of Paediatrics, Wagga Wagga Base Hospital, New South Wales, Australia.
⁸ Department of Paediatrics; Child and Youth Health, The University of Auckland; The National Immunisation Advisory Centre, The University of Auckland; Department of Infectious Diseases, Starship Children's Hospital, Auckland, New Zealand.
⁹ Department of Paediatrics, Child and Youth Health, The University of Auckland; Department of Infectious Diseases Starship Children's Hospital, Auckland, New Zealand; Department of Paediatrics, Kidz First Hospital, Auckland, New Zealand.
¹⁰ Department of Paediatrics, Child and Youth Health, The University of Auckland; Department of Infectious Diseases, Starship Children's Hospital, Auckland, New Zealand.
¹¹ Department of Infectious Disease, Barwon Health, Geelong, Australia; School of Medicine, Deakin University, Geelong, Australia.
¹² Sydney Medical School and Marie Bashir Institute, University of Sydney, NSW, Australia; Department of Infectious Diseases and Microbiology, the Children's Hospital at Westmead, Sydney, Australia.
¹³ Infectious Diseases Unit, Department of General Medicine, The Royal Children's Hospital, Parkville, Victoria, Australia; Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
¹⁴ Department of Infectious Diseases, Perth Children's Hospital, Nedlands, Western Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia; University of Western Australia. School of Medicine, Perth, Western Australia.
¹⁵ Infection and Immunity, Monash Children's Hospital, Monash Health, Clayton, Victoria, Australia; Department of General Paediatrics, Monash Children's Hospital, Monash Health, Victoria, Australia; Department of Paediatrics, Monash University, Clayton, Australia.
¹⁶ Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia; Department of Paediatrics, Royal Darwin Hospital, Darwin, Australia.
¹⁷ Department of Paediatrics, Royal Darwin Hospital, Darwin, Australia.
¹⁸ Queensland Children's Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Australia.
¹⁹ Infection & Immunity, Monash Children's Hospital, Monash Health, Clayton, Victoria, Australia; Department of Paediatrics, Monash University, Clayton, Australia; Monash Infectious Diseases, Monash Health, Clayton, Victoria, Australia.
²⁰ Department of Infectious Disease, Barwon Health, Geelong, Australia.
²¹ Infectious Diseases Department, Women's and Children's Hospital, Adelaide.
²² Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Sydney, Australia; School of Women's and Children's Health, University of New South Wales, Sydney, Australia; National Centre for Infections in Cancer, University of Melbourne, Melbourne, Australia.
²³ Department of Infectious Diseases, Perth Children's Hospital, Nedlands; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute; School of Medicine, University of Western Australia, Subiaco; Menzies School of Health Research, Charles Darwin Hospital, Darwin, NT.
²⁴ Department of Infectious Diseases, Perth Children's Hospital, Nedlands; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute and School of Medicine, University of Western Australia; Department of Microbiology, PathWest Laboratory Medicine, QEII Medical Centre, Perth, Western Australia.

PMID: 35342022
DOI: 10.1016/j.jgar.2022.03.012

Abstract

Objectives: The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration.

Methods: A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017-2018). Whole genome sequencing (WGS) data were paired with clinical information from the ISAIAH cohort.

Results: 353 SAB isolates were sequenced; 85% methicillin-susceptible S. aureus ([MSSA], 301/353) and 15% methicillin-resistant S. aureus ([MRSA], 52/353). There were 92 sequence types (STs), most commonly ST5 (18%) and ST30 (8%), grouped into 23 clonal complexes (CCs), most frequently CC5 (21%) and CC30 (12%). MSSA comprised the majority of healthcare-associated SAB (87%, 109/125), with principal clones CC15 (48%, 11/21) and CC8 (33%, 7/21). Panton-Valentine leukocidin (PVL)-positive SAB occurred in 22% (76/353); predominantly MSSA (59%, 45/76), community-onset (92%, 70/76) infections. For community-onset SAB, the only microbiological independent predictor of poor outcomes was PVL positivity (aOR 2.6 [CI 1.0-6.2]).

Conclusion: From this WGS paediatric SAB data, we demonstrate the previously under-recognized role MSSA has in harbouring genetic virulence and causing healthcare-associated infections. PVL positivity was the only molecular independent predictor of poor outcomes in children. These findings underscore the need for further research to define the potential implications PVL-producing strains may have on approaches to S. aureus clinical management.

Keywords: Bacteraemia; Molecular; Outcomes; Paediatrics; Staphylococcus aureus; Whole genome sequencing.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Australia / epidemiology
Bacteremia* / epidemiology
Bacteremia* / microbiology
Child
Humans
Methicillin-Resistant Staphylococcus aureus*
Molecular Epidemiology
Prospective Studies
Staphylococcal Infections* / epidemiology
Staphylococcal Infections* / microbiology
Staphylococcus aureus
Whole Genome Sequencing