Evaluation of the prevalence of xylazine and etiology of xylazine related invasive infections

ABSTRACT / PROJECT SUMMARY Xylazine is an alpha 2 adrenergic receptor agonist with sedative and analgesic properties which is increasingly being found in the US illegal drug supply and linked to numerous adverse health outcomes including overdose deaths, skin ulcerations and infections. Public health efforts are limited by a lack of data on the type of illicit controlled substances that have been adulterated by xylazine, while at the same time clinicians face an increasing number of patients presenting with large painful skin ulcerations, many of which are complicated by necrotizing infections or underlying osteomyelitis. However, it is unclear to what degree these xylazine related complications are the result of infections due to pathogens directly injected from a contaminated drug supply, compared with secondary superinfections from skin colonizing microbes of vasoconstriction mediated chemical injuries. Our proposed grant application seeks to fill this critical gap in the literature. In aim 1 we will conduct active surveillance of the local illicit drug supply in St. Louis Missouri using mass spectrometry and microbiologic cultures of syringe residue. This will allow us to identify the full spectrum of illicit drugs associated with xylazine while also performing ongoing surveillance for the potential emergence of any other novel adulterants. Microbiologic analyses of syringe residue will allow us to determine if xylazine contaminated illicit drugs support increased levels of bacterial contamination compared to other illicit drugs which might explain the high degree of invasive infections associated with this novel adulterant. Aim 2 will consent hospitalized patients with xylazine related invasive infections and compare bacterial pathogens isolated from clinical specimens with skin colonizing microflora and bacterial and fungal species isolated from xylazine containing syringe residue collected in Aim 1. By comparing core genome single nucleotide polymorphism (cgSNP) distances we will determine if clinical sites of infection are the result of bacterial superinfection from skin colonizing organisms or arose directly from bacterial species innoculated along with xylazine containing illicit drugs. The work proposed in this application has the potential to directly impact public health and patient care. A clear understanding of what pathogens people who use xylazine are routinely exposed to, and an increased understanding of the etiology of xylazine related infectious complications is urgently needed to guide public health policy and target harm reduction interventions.