Staphylococcus aureus injection drug use-associated bloodstream infections are propagated by community outbreaks of diverse lineages

The ongoing injection drug use (IDU) crisis in the United States has been complicated by an emerging epidemic of Staphylococcus aureus IDU-associated bloodstream infections (IDU-BSI). We performed a case-control study comparing S. aureus IDU-BSI and non-IDU BSI cases identified in a large US Midwestern academic medical center between Jan 1, 2016 and Dec 21, 2019. We obtained the whole-genome sequences of 154 S. aureus IDU-BSI and 91 S. aureus non-IDU BSI cases, which were matched with clinical data. We performed phylogenetic and comparative genomic analyses to investigate clonal expansion of lineages and molecular features characteristic of IDU-BSI isolates. Here we show that patients with IDU-BSI experience longer durations of bacteremia and have lower medical therapy completion rates. In phylogenetic analyses, 45/154 and 1/91 contemporaneous IDU-BSI and non-IDU BSI staphylococcal isolates, respectively, group into multiple, unique clonal clusters, revealing that pathogen community transmission distinctively spurs IDU-BSI. Lastly, multiple S. aureus lineages deficient in canonical virulence genes are overrepresented among IDU-BSI, which may contribute to the distinguishable clinical presentation of IDU-BSI cases. We identify clonal expansion of multiple S. aureus lineages among IDU-BSI isolates, but not non-IDU BSI isolates, in a community with limited access to needle exchange facilities. In the setting of expanding numbers of staphylococcal IDU-BSI cases consideration should be given to treating IDU-associated invasive staphylococcal infections as a communicable disease. Marks and Calix et al. perform a case-control genomic epidemiology study comparing Staphylococcus aureus isolates from intravenous drug use-associated bloodstream infections with those from other bloodstream infections. The authors show there is clonal expansion of lineages in intravenous drug use-associated bloodstream infections suggesting person-to-person transmission of S. aureus. Persons who inject drugs are at increased risk of developing a bloodstream infection caused by the bacterium Staphylococcus aureus. To investigate whether this risk is due to transmission of the bacterium within this community, we compared the complete set of genes (genome) of S. aureus isolated from people with bloodstream infections who do and do not inject drugs. S. aureus causing bloodstream infections in persons who inject drugs were much more likely to belong to one of multiple networks of very closely related subtypes, demonstrating that in some communities the bacteria causing this type of infection can likely be directly transmitted from person to person through high-risk injection drug use practices, such as sharing needles. Therefore, invasive infections in persons who inject drugs can spread like communicable diseases and this can inform future policy on how to prevent them.