Wednesday, April 2, 2025
4/2/2025
Examination of Xylazine Exposure and the Risk of Skin and Soft Tissue Infections in People Who Inject Drugs - Summary Alterations in the availability, potency, or composition of illicit drugs can lead to shifts in drug use behaviors and drug-related morbidity and mortality. Such changes can expose individuals to new risks, potentially increasing the likelihood of infection. In recent years, Xylazine, also known as tranq or tranq dope or anestesia de caballo, has significantly affected people who inject drugs (PWID). Xylazine, a phenothiazine, induces sedation, giving users a false perception of prolonged fentanyl effects. Xylazine has several adverse effects, including severe infections, skin ulceration, and prolonged sedation. However, little is known about how xylazine contributes to increased rates of severe skin and soft tissue infections (SSTI) among PWID. The possible explanations are allergic reactions to drug adulterants and other drug excipients or xylazine-driven vasoconstriction leading to decreased blood flow into the tissue leading to necrosis followed by skin infections. While there is a strong understanding of factors that are protective against SSTI, additional research is needed to understand if harm reduction measures such as use of clean syringes, good hygiene and stable housing are protective in the context of xylazine exposure. Additional challenges exist in measuring the exposure to xylazine. While tests that can identify xylazine and its metabolites in urine, drug paraphernalia, and drug samples, a single test cannot provide an accurate estimate of xylazine exposure as the drug supply is constantly changing. Therefore, there is a critical need to develop testing regimens to assess time varying exposures to xylazine and to then use the exposure data to better assess associations between xylazine exposure and SSTI incidence. We propose to prospectively recruit 200 PWID from Lowell, Massachusetts and follow them for a period of three months, quantifying exposure to xylazine and other drugs and measuring the incidence of SSTI. We will examine xylazine exposure among PWID using a combination of laboratory assessment, xylazine test strips, and urine analysis at multiple timepoints. We will then examine the incidence of SSTI among PWID in the study and determine the increased risk associated with xylazine use. In addition, we will use a qualitative research framework interviewing 15 PWID who develop SSTI and additional 15 PWID who do not develop SSTI to better understand the context surrounding SSTI risk factors and manifestations, as well as PWID healthcare interests, experiences, and challenges following SSTI. Our proposed mixed methods study will help identify the best assessments of exposure to xylazine and more precise associations between xylazine exposure and SSTI incidence, while also elucidating moderating and mediating risk factors.
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