A composite vignette: xylazine,infectious complications and the importance of community-based drug checking services

Abstract

Here we describe a composite vignette of a patient who developed necrotic wounds and systemic infection after reported exposure to xylazine, a veterinary anesthetic found as an adulterant in the unregulated drug supply. While exposure to xylazine-containing compounds via the use of fentanyl is not a new phenomenon, xylazine’s prevalence in overdose deaths has escalated, and its geographic distribution has expanded to include rural areas such as Maine. We use this composite vignette to highlight: (1) the growing number of overdoses in Maine where xylazine was found in combination with fentanyl, (2) the potential severe, infection-related complications of xylazine exposure, and (3) describe novel harm reduction strategies that utilize community- and laboratory-based drug checking technology.

Introduction

Xylazine, or “tranq,” is an alpha-2 adrenergic agonist used as a sedative in veterinary medicine.^1,2 Not approved for human use, xylazine has been found in the unregulated drug supply, notably with fentanyl, and increasingly detected in post-mortem toxicology reports among opioid overdose deaths.^3–5 Whether occurring incidentally or added systematically, the rationale for xylazine’s presence in the opioid supply is not well understood. ⁶ Its duration of effect appears to vary considerably between species, with an average half-life of 1 h in animals, compared to 12 h in humans.^7,8 A recent study in mice has demonstrated kappa-opioid receptor agonism, suggesting a potential synergistic role with fentanyl, which acts at the mu-opioid receptor. ⁹ At the same time, the role of naloxone as a direct reversal agent for xylazine remains poorly evidenced. ⁹ Nevertheless, since xylazine almost always appears in combination with fentanyl, naloxone remains a life-saving intervention. ¹⁰

Xylazine has been documented in the unregulated drug supply in Puerto Rico and Pennsylvania since the mid-2010s, and more recently in Maine in 2021.^11–13 In a few short years, the proportion of overdose deaths in Maine where xylazine was detected nearly doubled from 6% in 2022 to 11% in 2023. ¹² Among the 452 confirmed overdose deaths in 2024, in 65 of the cases (14%) both fentanyl and xylazine were detected. ¹² This trend is similar to elsewhere in the northeast, and, though trailing behind the mid-Atlantic region, far exceeds the national average, highlighting significant regional differences in xylazine prevalence.^13–15

Separate from overdose events, the use of xylazine-containing substances has been associated with severe wounds that can predispose individuals to skin, soft tissue, bone, bloodstream, and cardiac infections.^16–18 Should xylazine persist in the unregulated drug supply, such infectious complications of xylazine exposure may become more prevalent, especially in rural areas, such as Maine, where access to healthcare is limited. Thus, effective harm reduction strategies aimed at xylazine detection and wound care are valuable approaches to increasing safety for people who use drugs.

In this report we: (1) present a composite vignette involving a patient with Methicillin-sensitive Staphylococcus aureus (MSSA) infective endocarditis that likely occurred as a consequence of xylazine-associated wounds; (2) describe “drug checking” as an upstream, primary preventive strategy that allows people who use drugs an opportunity to screen their substances before use and (3) explore current rapid-testing and laboratory-quality drug checking methods being deployed in Maine. To ensure that our observations reflect a valuable contribution to the existing body of literature, this study was conducted and reported in accordance with the CARE guidelines (Supplemental Appendix 1).

Composite vignette: Main symptoms and clinical findings

The following composite vignette was assembled using details from multiple de-identified patient cases that were under the direct care of authors LJ and KT. The use of this methodology allows the authors to highlight several medically and socially important aspects while maintaining patient privacy. ¹⁹

In 2023, a woman with a past medical history significant for chronic hepatitis C, ongoing housing insecurity, and polysubstance use—primarily injection of opioids and stimulants—presented to a tertiary care center in Maine with fever, tachycardia, tachypnea, and hypoxia. She reported several weeks of increased weakness, chills, and fatigue that prevented her from ambulating. She reported having used “tranq” (i.e., xylazine) and associated its use with the development of wounds on her legs. She reported the presence of the wounds as early as 2021, and on review of outpatient medical records, it seemed that the patient delayed seeking medical attention, in part due to fear of lower extremity amputation.

Her exam was notable for impressive, crusted, necrotic-appearing bilateral lower extremity wounds with surrounding erythema and purulence as well as islands of spared normal skin. With ulceration and black eschar covering a large portion of the wounds, it was evident the wounds were chronic and had only recently become infected. Initially, two out of two blood culture bottles were positive for MSSA. Blood cultures remained positive for 10 days. After a comprehensive workup that included cross-sectional imaging and transesophageal echocardiography, the patient was diagnosed with bilateral lower extremity cellulitis, septic shock secondary to MSSA bacteremia, psoas and hand abscesses, tricuspid valve infective endocarditis, and acute hypoxic respiratory failure in the setting of extensive septic pulmonary emboli and superimposed pneumonia. She was treated with cefazolin 2 g intravenously every 8 h. Initial wound care involved debridement and removal of overlying eschar, followed by frequent dressing changes with cleansing soaks, medical-grade honey, and nonadherence dressings. Early assessment by cardiothoracic surgery favored a short trial of medical management with IV cefazolin prior to pursuing surgical intervention. AngioVac-assisted vegetation debulking was considered, though ultimately deemed futile in the setting of further decline. ²⁰ As medical therapy proved insufficient to change disease trajectory, particularly with respect to respiratory status, the patient’s family elected to pursue comfort-directed care.

To summarize, the patient described in this composite vignette developed chronic skin wounds after presumed exposure to xylazine, likely via the use of injection drugs. These wounds were slow to heal and predisposed her to infection of the skin. When she did develop an infection, the bacteria entered her bloodstream and infected her heart valve and lungs. These complications led to respiratory failure and necessitated the use of a ventilator. Throughout hospitalization, treatment was attempted with antibiotics, but ultimately could not prevent the patient’s death.

Discussion

Xylazine-associated wounds and related complications have been documented broadly since its domestic debut in the unregulated drug supply almost two decades ago. Our composite vignette describes xylazine-related infective endocarditis in Maine and serves as a humanizing complement to ongoing statewide reporting. ¹² It highlights severe life-threatening complications of xylazine exposure that are likely to become more common if xylazine persists in the unregulated drug supply, and while access to preventive care is limited. This composite vignette demonstrates an opportunity to improve clinical outcomes by supporting and enhancing access to low-barrier harm reduction services, specifically wound care resources and tools for substance screening.^21,31

Severe, necrotic wounds, such as those detailed in this composite vignette, are consistent with other examples documented previously.^22–25 Hallmark features include areas of slowly healing ulceration and necrotic eschar with islands of normal tissue. Interestingly, xylazine-associated wounds can develop independently of injection site or route of administration; wound biopsies may therefore be nonspecific (showing inflammation and necrosis) and also not practical to perform in low-barrier clinical settings.^22,23,26 In the context of this composite vignette, post-mortem blood or urine testing might have revealed recent xylazine exposure, but could not confirm the etiology of her chronic wounds. As such, clinicians rely on patient testimony and a high degree of clinical suspicion when attributing wound development to xylazine exposure.

Extensive soft tissue involvement of the wounds posed serious risks for the development of the infectious complications described in this clinical vignette. The patient may have developed high-grade MSSA bacteremia and resultant endocarditis due to translocation of skin flora into the bloodstream at wound sites. Alternatively, it is possible she developed bacteremia via direct inoculation through the use of nonsterile intravenous needles. Each scenario highlights a role for harm reduction, namely through wound care services and safe injection supplies, which may minimize the risk of local and systemic infection.^25,26

It is notable that the patient described in this composite vignette intermittently accessed care at a low-barrier outpatient clinic. This particular clinic offers walk-in and follow-up care, case management, mental health services, dental care, substance use treatment, and wound care. ²⁷ During routine visits, the patient was offered examination as well as Xeroform rolls, gauze wraps, and 3M^™ Coban,^™ considered standard of care for the treatment of xylazine wounds. ²⁶ Unfortunately, despite receiving wound care instruction and encouragement to seek higher levels of care, the patient struggled to change dressings with regularity, likely predisposing her to infection. This is perhaps due to more systemic barriers such as housing instability and incomplete care coordination, or stigma, whether enacted, anticipated, or internalized.^28–31

The patient’s wounds may have been avoided altogether if she had a reliable way to test her substances for xylazine. People who use drugs have found various ways to detect contaminants to make drug use as safe as possible. They might taste or smell their drugs to check for any abnormalities, visually inspect drugs for any unsuspected colors, do a small tester shot to verify it provides the intended or sought-after effect, ask friends how their experiences were with the drug, and use other methods.^32–34 Today, the process of “drug checking” has become an important primary preventive strategy of harm reduction programs.^33,34 It has been observed that empowering people who use drugs, through community-based drug checking and learning about the chemical composition of their drugs, may influence drug use behaviors in ways that reduce harm (reduce or avoid use, or change suppliers).^32,33 Prior work has shown that people who use drugs both support and use drug checking services when embedded within syringe services programs or low-barrier settings, such as the services our patient accessed.^34,35 The low-barrier clinic where our patient accessed care provides rapid lateral flow immunoassay fentanyl test strips that utilize antibody-antigen binding to signal the presence of a contaminant.^36,37 Such test strip technology has been developed to reliably identify fentanyl, but has significant limitations with respect to xylazine. Xylazine test strips have been shown to (a) have too high a level of detection (i.e., do not identify xylazine at low concentrations), (b) require a large sample, (c) induce cross-reactivity with lidocaine which generates false positive results, (d) have poor sensitivity which leads to false negatives, and (e) while accessible through online vendors, costs can vary.^38–40 Together, these limitations undermine the use of xylazine test strips as an isolated public health strategy; their distribution at low-barrier healthcare centers may not have reliably helped our patient avoid xylazine exposure. To address these issues, harm reduction programs in Maine and elsewhere are deploying novel testing strategies using laboratory-grade technology in conjunction with xylazine test strips.

Fourier-transform infrared spectroscopy (FTIR) instruments allow on-site, real-time point-of-care testing by harm reduction programs. Ideally, programs partner for additional laboratory testing to conduct off-site advanced testing: liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). In contrast to test strips, FTIR and GC-MS can identify multiple components in a drug sample and quantify their relative abundance with gold-standard accuracy. Crucially, while test strips only detect specific substances, such as fentanyl or xylazine, FTIR and GC-MS may detect an extensive range of substances, including adulterants, rare psychoactive compounds, and cutting agents. This increased capability does come at a cost—one study estimates about $500 per drug checked—however, low-barrier access to such FTIR- and MS-based testing methods could have an immediate impact in alleviating the challenges of a contaminated drug supply. ⁴⁰

In Maine, community-based FTIR instruments and off-site laboratory testing are now being deployed as a new and unique collaboration between syringe services programs, a not-for-profit integrated health system, and academic and other community partners as part of a statewide drug checking program. ⁴¹ This, and other initiatives, have been made possible by supportive partners in Maine, which also include state agencies, healthcare leaders, and numerous nonprofit organizations. Together, they have mobilized state, federal, and opioid settlement funds to expand capacity for substance use care, including harm reduction. They also worked with government and public health partners to draft, advocate for, and pass legislation to allow drug checking through community programs in Maine (LD 1745 “An Act to Support Public Health by Clarifying Authorized Activities Regarding Drug Checking”). ⁴² Syringe services programs also obtained additional funding to support a mobile unit to conduct drug checking in rural Maine counties. Some practical considerations for operating drug checking services in rural areas, such as Maine, include budgeting for costs such as FTIRs, mobile units, staff time to perform drug checking outreach, as well as costs of mailing samples for complementary (i.e., LC-MS or GC-MS) testing.

Inevitably, there are, and will continue to be, waves of contaminants in the unregulated drug supply besides xylazine. While desomorphine (synthetic opioid) and levamisole (anti-helminthic) were commonly found in the unregulated drug supply prior to xylazine emerging, most recently, “BTMPS” (bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate—an industrial chemical) and nitazenes (synthetic opioids) have both been identified in some locations across the United States, including rural areas. ⁴³ Drug checking services are thus essential to inform PWUD and their communities as the unregulated drug supply continues to change over time.

Conclusion

Paired with consistent access to wound care supplies and non-stigmatizing care, real-time information about the chemical composition of the drug supply can minimize harm for people who use drugs and may have changed our patients’ outcomes. Exploring the use of these services by people who use drugs and their role in avoiding wounds, hospitalizations, and mortality, particularly in rural areas, should be a public health priority. As the unregulated drug supply changes over time and new contaminants emerge, drug checking services can serve as an important public health tool to help inform people who use drugs and their communities.

Supplemental Material

sj-docx-1-tai-10.1177_20499361251365090 – Supplemental material for A composite vignette: xylazine, infectious complications and the importance of community-based drug checking services

Supplemental material, sj-docx-1-tai-10.1177_20499361251365090 for A composite vignette: xylazine, infectious complications and the importance of community-based drug checking services by Liam John, Nathaniel Flint, Francesca Piccolo, Katherine Hill, Marion Anderson, Brian Townsend, Michael Fletcher, Cole Altomare-Jarczyk, Kristen Silvia, Traci Green, Dasan Thamattoor, Jean Bessette and Kinna Thakarar in Therapeutic Advances in Infectious Disease