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

Abstract

Recently, we identified a Staphylococcus aureus 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 S. aureus strains. We collated Vitek 2 susceptibility data for S. aureus 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 S. aureus isolates, non-multidrug-resistant methicillin-resistant S. aureus (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 dfrG within SCCmec 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-SCCmec IVo clone that is SXT susceptible by Etest and causes clinical disease similar to that caused by ST93-MRSA-SCCmec IVa. Reliance on Vitek 2 SXT reporting may lead to unnecessary restriction of effective oral treatment options for S. aureus infections. Whether the presence of dfrG within SCCmec IVo provides a selective advantage at the population level is currently unclear. IMPORTANCE Staphylococcus aureus 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 S. aureus strains with specific virulence factors and resistance to beta-lactam antibiotics. Recently, an S. aureus strain with discrepant antimicrobial susceptibility testing results has emerged in northern Australia. This ST5-MRSA-SCCmec IVo clone is reported as resistant to trimethoprim-sulfamethoxazole by Vitek 2 but susceptible by phenotypic methods. ST5-MRSA-SCCmec 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-SCCmecIVo is causing a clonal outbreak across a large geographical region. Although phenotypic testing suggests in vitro susceptibility to trimethoprim-sulfamethoxazole, it is unclear at this stage whether the presence of dfrG within SCCmec IVo provides a selective advantage at the population level.

Methicillin-resistant Staphylococcus aureus in China: a multicentre longitudinal study and whole-genome sequencing

“…pvl was only carried by a small proportion of isolates, and there was no significant association with CA-MRSA lineage ST59 in our data. The presence of PVL has previously been strongly associated with CA-MRSA in many studies [ 49 , 50 ], while the findings of our study do not support this notion. Most of ST338, CC30, CC398, ST8 and CC22 carried pvl in the present study, demonstrating the pathogenic potential of these MRSA lineages.…”

Molecular Mechanisms of Drug Resistance in Staphylococcus aureus

“…1, LC425379.1); IVm (JCSC8843-AB872254); IVn (ST93-KX385846. 1); IVo [ 28 , 32 , 37 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ]; Va (WIS(WBG8318)-AB121219); Vb (TSGH17, JCSC7190), PM1, JCSC5952-AB512767, AB462393, AB478780); Vc (S0385, JCSC6944-AM990992, AB505629) [ 26 , 45 , 52 , 67 ].…”

and

“…ST93 has disseminated throughout Australia and much of New Zealand 10 and is often isolated from health care facilities as well as the general community. 6 More recent is the emergence of a CC5 PVL+ CA-MRSA strain, also in north-western or northern Australia, and this appears to be in the expansion phase 11 perhaps repeating what was seen with ST93. Other PVL+ strains of current or recent significance in northern Australia include a ST30 MRSA that has long been associated with the Pacific region, and has reduced in prevalence in recent years, 8,12 and ST121 (CC121), which is a PVL+ strain mainly associated with south-east and east Asia, and almost always MSSA.…”