{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:44:51Z","timestamp":1792712691653,"version":"4.5.0"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T00:00:00Z","timestamp":1660521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003921","name":"Australian Government Department of Health","doi-asserted-by":"publisher","award":["D21-363218"],"award-info":[{"award-number":["D21-363218"]}],"id":[{"id":"10.13039\/501100003921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Background: Defined by the emergence of antibiotic resistant strains, Staphylococcus aureus is a priority bacterial species with high antibiotic resistance. However, a rise in the prevalence of penicillin-susceptible S. aureus (PSSA) bloodstream infections has recently been observed worldwide, including in Australia, where the proportion of methicillin-susceptible S. aureus causing bacteremia identified phenotypically as penicillin-susceptible has increased by over 35%, from 17.5% in 2013 to 23.7% in 2020. Objectives: To determine the population structure of PSSA causing community- and hospital-onset bacteremia in Australia and to evaluate routine phenotypic antimicrobial susceptibility methods to reliably confirm penicillin resistance on blaZ-positive S. aureus initially classified as penicillin-susceptible by the Vitek\u00ae 2 automated microbiology system. Results: Whole genome sequencing on 470 PSSA collected in the 2020 Australian Group on Antimicrobial Resistance Australian Staphylococcus aureus Sepsis Outcome Programme identified 84 multilocus sequence types (STs), of which 79 (463 isolates) were grouped into 22 clonal complexes (CCs). The dominant CCs included CC5 (31.9%), CC97 (10.2%), CC45 (10.0%), CC15 (8.7%), and CC188 (4.9%). Many of the CCs had multiple STs and spa types and, based on the immune evasion cluster type, isolates within a CC could be classified into different strains harboring a range of virulence and resistance genes. Phylogenetic analyses of the isolates showed most CCs were represented by one clade. The blaZ gene was identified in 45 (9.6%) PSSA. Although multiclonal, approximately 50% of blaZ-positive PSSA were from CC15 and were found to be genetically distant from the blaZ-negative CC15 PSSA. The broth microdilution, Etest\u00ae and cefinase, performed poorly; however, when the appearance of the zone edge was considered; as per the EUCAST and CLSI criteria, disc diffusion detected 100% of blaZ-positive PSSA. Conclusions: In Australia, PSSA bacteremia is not caused by the expansion of a single clone. Approximately 10% of S. aureus classified as penicillin-susceptible by the Vitek\u00ae 2 harbored blaZ. Consequently, we recommend that confirmation of Vitek\u00ae 2 PSSA be performed using an alternative method, such as disc diffusion with careful interpretation of the zone edge.<\/jats:p>","DOI":"10.3390\/microorganisms10081650","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T20:58:08Z","timestamp":1660597088000},"page":"1650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Molecular Epidemiology of Penicillin-Susceptible Staphylococcus aureus Bacteremia in Australia and Reliability of Diagnostic Phenotypic Susceptibility Methods to Detect Penicillin Susceptibility"],"prefix":"10.3390","volume":"10","author":[{"given":"Geoffrey W.","family":"Coombs","sequence":"first","affiliation":[{"name":"Antimicrobial Resistance and Infectious Diseases (AMRID) Research Laboratory, Murdoch University, Murdoch, WA 6150, Australia"},{"name":"Department of Microbiology, PathWest Laboratory Medicine-WA, Fiona Stanley Hospital, Murdoch, WA 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7017-5146","authenticated-orcid":false,"given":"Nicholas W. T.","family":"Yee","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance and Infectious Diseases (AMRID) Research Laboratory, Murdoch University, Murdoch, WA 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Daley","sequence":"additional","affiliation":[{"name":"Department of Microbiology, PathWest Laboratory Medicine-WA, Fiona Stanley Hospital, Murdoch, WA 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9581-1612","authenticated-orcid":false,"given":"Catherine M.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Institute of Health Transformation, Deakin University, Melbourne, VIC 3125, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7563-6180","authenticated-orcid":false,"given":"James O.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance and Infectious Diseases (AMRID) Research Laboratory, Murdoch University, Murdoch, WA 6150, Australia"},{"name":"Department of Microbiology, PathWest Laboratory Medicine-WA, Fiona Stanley Hospital, Murdoch, WA 6150, Australia"},{"name":"Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, WA 6150, Australia"},{"name":"Department of Infectious Diseases, Royal Perth Hospital, Perth, WA 6003, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0321-1180","authenticated-orcid":false,"given":"Marc","family":"Stegger","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance and Infectious Diseases (AMRID) Research Laboratory, Murdoch University, Murdoch, WA 6150, Australia"},{"name":"Department of Bacteria, Parasites and Fungi, Statens Serum Institute, 2300 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9643-9311","authenticated-orcid":false,"given":"Princy","family":"Shoby","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance and Infectious Diseases (AMRID) Research Laboratory, Murdoch University, Murdoch, WA 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9408-6068","authenticated-orcid":false,"given":"Shakeel","family":"Mowlaboccus","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance and Infectious Diseases (AMRID) Research Laboratory, Murdoch University, Murdoch, WA 6150, Australia"},{"name":"Department of Microbiology, PathWest Laboratory Medicine-WA, Fiona Stanley Hospital, Murdoch, WA 6150, Australia"},{"name":"School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1128\/CMR.00134-14","article-title":"Staphylococcus aureus infections: Epidemiology, pathophysiology, clinical manifestations, and management","volume":"28","author":"Tong","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.2217\/fmb.09.30","article-title":"Genetics of antimicrobial resistance in Staphylococcus aureus","volume":"4","author":"Jensen","year":"2009","journal-title":"Future Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1126\/science.99.2579.452","article-title":"Extraction of a Highly Potent Penicillin Inactivator from Penicillin-resistant Staphylococci","volume":"99","author":"Kirby","year":"1944","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S0140-6736(48)92166-7","article-title":"Infection by penicillin-resistant staphylococci","volume":"2","author":"Barber","year":"1948","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3201\/eid0702.010204","article-title":"The changing epidemiology of Staphylococcus aureus?","volume":"7","author":"Chambers","year":"2001","journal-title":"Emerg. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/j.amjmed.2016.01.048","article-title":"Back to the Future: Penicillin-Susceptible Staphylococcus aureus","volume":"129","author":"Cheng","year":"2016","journal-title":"Am. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jinf.2016.05.011","article-title":"The prevalence, population structure and screening test specificity of penicillin-susceptible Staphylococcus aureus bacteremia isolates in Malmo, Sweden","volume":"73","author":"Resman","year":"2016","journal-title":"J. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00680-18","DOI":"10.1128\/AAC.00680-18","article-title":"Increasing Rates of Penicillin Sensitivity in Staphylococcus aureus","volume":"62","author":"Lee","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","first-page":"3353","article-title":"Reappearance and treatment of penicillin-susceptible Staphylococcus aureus in a tertiary medical centre","volume":"70","author":"Chabot","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1080\/22221751.2022.2027218","article-title":"Genomic epidemiology and characterisation of penicillin-sensitive Staphylococcus aureus isolates from invasive bloodstream infections in China: An increasing prevalence and higher diversity in genetic typing be revealed","volume":"11","author":"Jin","year":"2022","journal-title":"Emerg. Microbes. Infect."},{"key":"ref_11","first-page":"2018","article-title":"Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) Annual Report 2020","volume":"46","author":"Coombs","year":"2022","journal-title":"Commun. Dis. Intell."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.ijantimicag.2019.05.020","article-title":"Benzylpenicillin versus flucloxacillin for penicillin-susceptible Staphylococcus aureus bloodstream infections from a large retrospective cohort study","volume":"54","author":"Henderson","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1161\/CIR.0000000000000296","article-title":"Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association","volume":"132","author":"Baddour","year":"2015","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1128\/JCM.03068-13","article-title":"Performance of phenotypic tests for detection of penicillinase in Staphylococcus aureus isolates from Australia","volume":"52","author":"Papanicolas","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1080\/1120009X.1990.11738974","article-title":"Comparison of the efficiency of three methods for the determination of staphylococcal beta-lactamase","volume":"2","author":"Banic","year":"1990","journal-title":"J. Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/j.1469-0691.2008.01997.x","article-title":"Comparison of phenotypic methods for penicillinase detection in Staphylococcus aureus","volume":"14","author":"Kaase","year":"2008","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_17","unstructured":"James, S.L., PharmD, and FIDSA (2022). M100-ED31:2021. Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [31st ed.]. Available online: http:\/\/em100.edaptivedocs.net\/GetDoc.aspx?doc=CLSI%20M100%20ED31:2021&xormat=SPDF&src=BB."},{"key":"ref_18","unstructured":"(2021, August 01). Breakpoint Tables for Interpretation of MICs and Zone Diameters Version 11.0. Available online: http:\/\/www.eucast.org."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1128\/jcm.14.4.437-440.1981","article-title":"Correlation of penicillin minimum inhibitory concentrations and penicillin zone edge appearance with staphylococcal beta-lactamase production","volume":"14","author":"Gill","year":"1981","journal-title":"J. Clin. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1093\/jac\/dkab208","article-title":"Penicillin susceptibility among invasive MSSA infections: A multicentre study in 16 Spanish hospitals","volume":"76","author":"Mama","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jgar.2022.03.012","article-title":"Whole genome sequencing and molecular epidemiology of pediatric Staphylococcus aureus bacteremia","volume":"29","author":"Campbell","year":"2022","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e102","DOI":"10.1002\/cpbi.102","article-title":"Using SPAdes De Novo Assembler","volume":"70","author":"Prjibelski","year":"2020","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: Rapid prokaryotic genome annotation","volume":"30","author":"Seemann","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1093\/bioinformatics\/btv421","article-title":"Roary: Rapid large-scale prokaryote pan genome analysis","volume":"31","author":"Page","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1093\/molbev\/msab120","article-title":"MEGA11: Molecular Evolutionary Genetics Analysis Version 11","volume":"38","author":"Tamura","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"W293","DOI":"10.1093\/nar\/gkab301","article-title":"Interactive Tree Of Life (iTOL) v5: An online tool for phylogenetic tree display and annotation","volume":"49","author":"Letunic","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_27","unstructured":"(2022, February 01). Mlst, Github. Available online: https:\/\/github.com\/tseemann\/mlst."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"124","DOI":"10.12688\/wellcomeopenres.14826.1","article-title":"Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications","volume":"3","author":"Jolley","year":"2018","journal-title":"Wellcome Open Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1101\/gr.232397.117","article-title":"GrapeTree: Visualization of core genomic relationships among 100,000 bacterial pathogens","volume":"28","author":"Zhou","year":"2018","journal-title":"Genome Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e00483-19","DOI":"10.1128\/AAC.00483-19","article-title":"Validating the AMRFinder Tool and Resistance Gene Database by Using Antimicrobial Resistance Genotype-Phenotype Correlations in a Collection of Isolates","volume":"63","author":"Feldgarden","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1093\/jac\/dkx217","article-title":"PointFinder: A novel web tool for WGS-based detection of antimicrobial resistance associated with chromosomal point mutations in bacterial pathogens","volume":"72","author":"Zankari","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e02511-19","DOI":"10.1128\/AAC.02511-19","article-title":"Novel Insights into the Classification of Staphylococcal beta-Lactamases in Relation to the Cefazolin Inoculum Effect","volume":"64","author":"Carvajal","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","unstructured":"(2021, August 01). BD BBL\u2122 Cefinase\u2122 Paper Discs. Available online: https:\/\/www.bd.com\/en-ca\/offerings\/capabilities\/microbiology-solutions\/identification-and-susceptibility-testing\/bd-bbl-sensi-disc-products\/bd-bbl-cefinase-paper-discs."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jinf.2017.07.010","article-title":"Genomic epidemiology of methicillin-susceptible Staphylococcus aureus across colonisation and skin and soft tissue infection","volume":"75","author":"Grinberg","year":"2017","journal-title":"J. Infect."},{"key":"ref_36","first-page":"E309","article-title":"Australian Staphylococcus aureus Sepsis Outcome Programme annual report, 2013","volume":"38","author":"Coombs","year":"2014","journal-title":"Commun. Dis. Intell. Q. Rep."},{"key":"ref_37","first-page":"203","article-title":"Slipped-strand mispairing: A major mechanism for DNA sequence evolution","volume":"4","author":"Levinson","year":"1987","journal-title":"Mol. Biol. Evol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1093\/jac\/dkab032","article-title":"Evaluation of methods for detection of beta-lactamase production in MSSA","volume":"76","author":"Skov","year":"2021","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/8\/1650\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:09:03Z","timestamp":1760141343000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/8\/1650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,15]]},"references-count":38,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["microorganisms10081650"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms10081650","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,15]]}}}