Diagnostic performance of xylazine test strips in urine from fentanyl-positive hospitalized patients

INTRODUCTION: Xylazine is an α-2-adrenergic agonist increasingly detected in the illicit drug supply, particularly in combination with fentanyl, yet no FDA-cleared rapid diagnostic assay exists for detection in biological specimens. Commercially available xylazine test strips, developed to evaluate drug samples, have been proposed for clinical use. We aim to evaluate the clinical screening performance of xylazine test strips when applied to urine specimens from hospitalized patients with fentanyl-positive routine hospital urine drug screening. METHODS: This single-center diagnostic accuracy study included 250 consecutive residual urine specimens from hospitalized patients with fentanyl-positive routine hospital urine drug screening. Fentanyl positivity was not confirmed by hospital liquid chromatography-mass spectrometry. Each specimen underwent testing with a commercially available xylazine test strips and liquid chromatography-mass spectometry for xylazine detection and quantification as the reference standard. Sensitivity, specificity, predictive values, likelihood ratios, and exact 95% confidence intervals (CIs) were calculated. RESULTS: Liquid chromatography-mass spectometry detected xylazine in 71 of 250 specimens (28.4%). Xylazine test strips identified 19 true positives, 139 true negatives, 40 false positives, and 52 false negatives. Sensitivity was 26.8% (95% CI 16.9-38.6%), and specificity was 77.7% (95% CI 70.8-83.5%). Positive and negative predictive values were 32.2% and 72.8%, respectively. The positive likelihood ratio was 1.2 and the negative likelihood ratio was 0.94. Most LC-MS-positive specimens (91.5%) had xylazine concentrations below the manufacturer-reported xylazine test strips detection threshold of 1,000 ng/mL. DISCUSSION: When applied to urine specimens from hospitalized patients with fentanyl-positive routine hospital urine drug screens, commercially available xylazine test strips demonstrated limited diagnostic utility, largely due to low sensitivity at clinically observed concentration ranges. Xylazine test strips results should not be used in isolation to guide clinical decision-making until validated point-of-care assays designed for biological specimens become available. CONCLUSION: Commercially available xylazine test strips demonstrate poor clinical screening performance when applied to urine specimens from hospitalized patients with fentanyl-positive routine hospital urine drug screens.