Drug use equipment and skin colonization facilitate Staphylococcus aureus bloodstream infection and reinfection

It is unknown if Staphylococcus aureus bacteremia (SAB) in people who inject drugs is a result of concomitant skin colonization or re-use of contaminated drug use equipment. Further, it remains unclear whether repeat instances of SAB among people who inject drugs are related to relapse of infections with the same S. aureus strain or reinfection by unrelated S. aureus strains. We prospectively recruited 101 patients with SAB, including 50 patients who inject drugs. We used hybrid assembly of short- and long-read whole genome sequencing (WGS) data to compare whole genome single nucleotide polymorphism (wgSNP) differences between blood culture, colonization, drug use equipment, and community syringe S. aureus isolates to assess for clonality (≤20 wgSNP). Plasmidic contigs from WGS of isolates that shared ≥ 99.9% average nucleotide identity with other plasmids were identified as instances of potential plasmid transmission. Hospitalized individuals with SAB and no reported drug use were analyzed as a comparator. Clinical data and hospitalization history were abstracted from the electronic medical record. Bloodstream isolates from people who inject drugs with two or more admissions for SAB between 2016 and 2024 with available isolates of sufficient quality ( n = 47) were sequenced and assessed for clonality. We identified that 22% of SAB isolates from people who inject drugs in the prospective colonization study were related to colonization isolates and 11% to isolates recovered from drug use equipment or discarded syringes. Network analysis revealed that potential plasmid transmission events were primarily driven by injection drug use related isolates (61.2%), MRSA status (72.6%), and sequence type (ST) group 8/1181 isolates (62.4%). Among patients hospitalized with multiple admissions for recurrent SAB, 63.8% were attributed to relapse with related isolates. SAB may result from nonsterile injection practices that facilitate infection with colonizing organisms, as well as shared fomites or common environments. These practices and factors may also contribute to local spread of S. aureus strains among people who inject drugs.