Wastewater Surveillance for Xylazine in Kentucky

•Wastewater surveillance detected xylazine in Kentucky in the absence of more traditional signals.•Xylazine was in 62% of daily wastewater samples across multiple site types.•A comprehensive drug wastewater surveillance strategy is needed in the U.S. In the U.S., xylazine, the veterinary non-opioid sedative, has emerged as a major threat to people who use illicitly manufactured fentanyl and other drugs. The aim of this study was to compare wastewater detection of xylazine with other public health and safety surveillance data from 2019 to 2023 in Kentucky. Wastewater samples from 5 rest areas, 2 truck weigh stations, and 4 wastewater treatment plants were tested for xylazine. Wastewater xylazine positivity rates were compared with xylazine-positive submission rates from the National Forensic Laboratory Information System and Kentucky's fatal overdoses in 6-month periods (Period 1=January–June; Period 2=July–December). Xylazine was detected in 61.6% (424 of 688) of daily wastewater samples from roadway sites/wastewater treatment plants. For roadways, detection increased from 55% (Period 1, 2021) to 94% (Period 1, 2023), and wastewater treatment plants had an overall detection of 25.8% (n=66 samples, Periods 1 and 2, 2022). Increasing roadway positivity corresponded to trends in National Forensic Laboratory Information System xylazine-positive submission rates: from 0.19 per 1,000 submissions (Period 1, 2019) to 2.9 per 1,000 (Period 2, 2022, latest available). No deaths from xylazine were reported publicly in Kentucky, although this study's authors identified 1–4 deaths (true count suppressed) in the overdose surveillance system, which, in back-of-the-envelope comparisons with other states, is far fewer than expected. Wastewater signals indicate broad geographic exposure to xylazine in Kentucky, yet health outcomes data suggest otherwise. These findings may inform regional, national, and international efforts to incorporate wastewater-based drug surveillance. Harm-reduction activities along roadways and other suitable locations may be needed.