A multi-site, international laboratory study to assess the performance of penicillin susceptibility testing of Staphylococcus aureus
Authors: Henderson Andrew , Cheng Matthew P , Chew Ka Lip , Coombs Geoffrey W , Davis Joshua S , Grant Jennifer M , Gregson Dan , Giulieri Stefano G , Howden Benjamin P , Lee Todd C , Nguyen Vi , Mora Jocelyn M , Morpeth Susan C , Robinson James O , Tong Steven Y C , Van Hal Sebastiaan J ,   Microbiology Working Group of the Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Group, 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 
Published: April 2023

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.