A multi-site, international laboratory study to assess the performance of penicillin susceptibility testing of Staphylococcus aureus

Author:

Henderson Andrew1,Cheng Matthew P2ORCID,Chew Ka Lip3,Coombs Geoffrey W4,Davis Joshua S56ORCID,Grant Jennifer M78,Gregson Dan9,Giulieri Stefano G1011,Howden Benjamin P1213ORCID,Lee Todd C14ORCID,Nguyen Vi15,Mora Jocelyn M15,Morpeth Susan C1617,Robinson James O1819,Tong Steven Y C1511ORCID,Van Hal Sebastiaan J2021ORCID,Abdul-Hameed Reem,Addidle Michael,Athan Eugene,Bloomfield Max,Bond Katherine,Botheras Carly,Bradbury Susan,Carignan Alex,Chan Wilson,Contronei Rose,Cooley Louise,Creighton Julie,Daley Peter,Daneman Nick,Diggle Matthew,Drinković Dragana,Elvy Juliet,Flett Nadine,Foo Hong,Frazer Jaimie,Ghanem-Zoubi Nesrin,Goodman Anna,Gregory Clair,Harkness Jock,Hoddle Melissa,Howard Julia,Jissam Ali,Kalan Kristin,Kalukottege Pankaja,Kelley Peter,Korman Tony M,Kozak Robert,Lagace-Wiens Philippe,Larrotta Adriana,Leong Queenie,Leroi Marcel,Lorenz David,Martin Philippe,Mathew Susy,McEwan Belinda,McGlinchey Andrew,McKew Genevieve,McMullan Brendan,Merlino John,Mrkusich Angela,Munroe Sean,Newton Peter,Parkes Leighanne O,Pollak Dina,Robinson Murray,Roessler Sharon,Russell Madeline,Satie Maria,Sharma Narinder,Sigal Mendelsohn,Streitberg Richard,Tan Vincent,van der Werff Koen,Virey Evangeline S,Wilson Heather,Yamarura Deb,Yu Yang,Ziochos Helen,

Affiliation:

1. Infection Management Services, Princess Alexandra Hospital , Brisbane , Australia

2. Department of Medicine, and Laboratory Medicine, McGill University Health Centre , Montreal , Canada

3. Department of Laboratory Medicine, National University Hospital , Singapore , Singapore

4. Department of Antimicrobial Resistance, and Infectious Diseases Research Laboratory, Murdoch University , Murdoch , Australia

5. Hunter Medical Research Institute, University of Newcastle , Newcastle , Australia

6. Department of Infectious Diseases, John Hunter Hospital , Newcastle , Australia

7. Department of Medicine, Vancouver Coastal Health , Vancouver , Canada

8. Department of Medicine, University of British Columbia , Vancouver , Canada

9. Department of Pathology, Laboratory Medicine, and Medicine, Cummings School of Medicine at The University of Calgary , Calgary , Canada

10. Department of Microbiology, and Immunology, The University of Melbourne , Melbourne , Australia

11. Victorian Infectious Diseases Services, The Royal Melbourne Hospital , Melbourne , Australia

12. Microbiological Diagnostic Unit Public Health Laboratory, The Peter Doherty Institute for Infection and Immunity , Melbourne , Australia

13. Department of Infectious Diseases, Austin Hospital , Heidelberg , Australia

14. Department of Medicine, McGill University , Montreal , Canada

15. Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne , Australia

16. Microbiology Laboratory, Middlemore Hospital (Counties Manukau Te Whatu Ora) , Otahuhu , New Zealand

17. Faculty of Medical and Health Sciences, University of Auckland , Auckland , New Zealand

18. Department of Infectious Diseases, Royal Perth Hospital , Perth , Australia

19. Department of Infectious Diseases, Fiona Stanley Hospital , Murdoch , Australia

20. Department of Microbiology, and Infectious Diseases, Royal Prince Alfred Hospital , Missenden Road, Camperdown, NSW 2050, Sydney , Australia

21. School of Medicine, The University of Sydney , Sydney , Australia

Abstract

Abstract Objectives There is clinical uncertainty over the optimal treatment for penicillin-susceptible Staphylococcus aureus (PSSA) infections. Furthermore, there is concern that phenotypic penicillin susceptibility testing methods are not reliably able to detect some blaZ-positive S. aureus. Methods Nine S. aureus isolates, including six genetically diverse strains harbouring blaZ, were sent in triplicate to 34 participating laboratories from Australia (n = 14), New Zealand (n = 6), Canada (n = 12), Singapore (n = 1) and Israel (n = 1). We used blaZ PCR as the gold standard to assess susceptibility testing performance of CLSI (P10 disc) and EUCAST (P1 disc) methods. Very major errors (VMEs), major error (MEs) and categorical agreement were calculated. Results Twenty-two laboratories reported 593 results according to CLSI methodology (P10 disc). Nineteen laboratories reported 513 results according to the EUCAST (P1 disc) method. For CLSI laboratories, the categorical agreement and calculated VME and ME rates were 85% (508/593), 21% (84/396) and 1.5% (3/198), respectively. For EUCAST laboratories, the categorical agreement and calculated VME and ME rates were 93% (475/513), 11% (84/396) and 1% (3/198), respectively. Seven laboratories reported results for both methods, with VME rates of 24% for CLSI and 12% for EUCAST. Conclusions The EUCAST method with a P1 disc resulted in a lower VME rate compared with the CLSI methods with a P10 disc. These results should be considered in the context that among collections of PSSA isolates, as determined by automated MIC testing, less than 10% harbour blaZ. Furthermore, the clinical relevance of phenotypically susceptible, but blaZ-positive S. aureus, remains unclear.

Funder

Australian National Health and Medical Research Council

New Zealand Health Research Council

Canadian Institutes of Health Research

Singapore National Medical Research Council

United Kingdom National Institutes of Health Research

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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