Clinical and Molecular Epidemiology of an Emerging Panton-Valentine Leukocidin-Positive ST5 Methicillin-Resistant Staphylococcus Aureus Clone in Northern Australia

Recently, we identified a sequence type 5 (ST5) clone in northern Australia with discrepant trimethoprim-sulfamethoxazole (SXT) susceptibility results. We aimed to identify isolates of this clone using Vitek 2 SXT resistance as a proxy and to compare its epidemiology with those of other circulating strains. We collated Vitek 2 susceptibility data for isolates collected through our laboratory and conducted a prospective, case-control study comparing clinical, microbiological, epidemiological, and genomic data for subsets of isolates reported as SXT resistant (cases) and SXT susceptible (controls) by Vitek 2. While overall SXT resistance rates remained relatively stable from 2011 to 2018 among 27,721 isolates, non-multidrug-resistant methicillin-resistant (MRSA) strains almost completely replaced multidrug-resistant MRSA strains as the predominant SXT-resistant MRSA phenotype. Demographic and clinical features of 51 case-control pairs were similar, but genotyping revealed stark differences: clonal complex 5 (CC5) MRSA predominated among SXT-resistant cases (34/51 [67%]), while CC93 MRSA predominated among susceptible controls (26/51 [51%]). All CC5 isolates were an ST5 clonal lineage that possessed the trimethoprim resistance gene within SCC IVo; all were SXT susceptible by Etest. The replacement of Vitek 2 reported SXT-resistant multidrug-resistant MRSA by non-multidrug-resistant MRSA appears related to the emergence of an ST5-MRSA-SCC IVo clone that is SXT susceptible by Etest and causes clinical disease similar to that caused by ST93-MRSA-SCC IVa. Reliance on Vitek 2 SXT reporting may lead to unnecessary restriction of effective oral treatment options for infections. Whether the presence of within SCC IVo provides a selective advantage at the population level is currently unclear. is an important human pathogen that causes a wide range of clinical infections. In the past 2 decades, an epidemic of community-associated skin and soft tissue infections has been driven by strains with specific virulence factors and resistance to beta-lactam antibiotics. Recently, an strain with discrepant antimicrobial susceptibility testing results has emerged in northern Australia. This ST5-MRSA-SCC IVo clone is reported as resistant to trimethoprim-sulfamethoxazole by Vitek 2 but susceptible by phenotypic methods. ST5-MRSA-SCC IVo is now the second most common community-associated MRSA clone in parts of Australia and causes a spectrum of clinical disease similar to that caused by the virulent ST93-MRSA lineage. Whole-genome sequence analysis demonstrates that ST5-MRSA-SCCIVo is causing a clonal outbreak across a large geographical region. Although phenotypic testing suggests susceptibility to trimethoprim-sulfamethoxazole, it is unclear at this stage whether the presence of within SCC IVo provides a selective advantage at the population level.