Machine Learning Prediction of Multidrug Resistance in Swine-Derived Campylobacter spp. Using United States Antimicrobial Resistance Surveillance Data (2013–2023)

<i>Campylobacter</i> spp. are leading causes of bacterial gastroenteritis globally. Swine are recognized as an important reservoir for this pathogen. The emergence of antimicrobial resistance (AMR) and multidrug resistance (MDR) in <i>Campylobacter</i> is a global health concern. Traditional methods for detecting AMR and MDR, such as phenotypic testing or whole-genome sequencing, are resource-intensive and time-consuming. In the present study, we developed and validated a supervised machine learning model to predict MDR status in <i>Campylobacter</i> isolates from swine, using publicly available phenotypic AMR data collected by NARMS from 2013 to 2023. Resistance profiles for seven antimicrobials were used as predictors, and MDR was defined as resistance to at least one agent in three or more antimicrobial classes. The model was trained on 2013-2019 isolates and externally validated using isolates from 2020, 2021, and 2023. Random Forest showed the highest performance (accuracy = 99.87%, Kappa = 0.9962) among five evaluated algorithms, which achieved high balanced accuracy, sensitivity, and specificity in both training and external validation. Our feature importance analysis identified erythromycin, azithromycin, and clindamycin as the most influential predictors of MDR among <i>Campylobacter</i> isolates from swine. Our temporally validated, interpretable model provides a robust, cost-effective tool for predicting MDR in <i>Campylobacter</i> spp. and supports surveillance and early detection in food animal production systems.