Background/Objectives: Antibiotic resistance (ABR) is a global crisis leading to increased mortality and economic burden. Antimicrobial stewardship (AMS) promotes responsible antibiotic use and prescribing practices to combat ABR. This study assessed the knowledge, awareness, and perceptions of final-year medical and pharmacy students in Saudi Arabia regarding antibiotic use, ABR, and AMS. Methods: A national cross-sectional survey was conducted from January to April 2024 using a 49-item questionnaire. The survey assessed knowledge of antibiotic use, ABR, and AMS using predefined scoring, while perceptions were evaluated with a 5-point Likert scale. Data were analyzed using descriptive statistics and Chi-square tests to explore associations between independent variables and outcomes. A logistic regression analysis identified factors associated with good knowledge, and results were reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Among 197 participants from 26 Saudi universities, pharmacy students comprised 73.1% of the sample. Good knowledge was observed in 44.7% for antibiotic use, 47.7% for ABR, and 52.8% for AMS. However, 28.4% lacked awareness of AMS, and 5.6% were unaware of ABR. Pharmacy students demonstrated significantly higher knowledge and confidence in AMS and antibiotic handling compared to medical students (p < 0.001). Higher knowledge was also associated with the university’s region and prior education on resistance or AMS during college. Conclusions: This study highlights significant gaps in knowledge and awareness of antibiotic use, ABR, and AMS among final-year medical and pharmacy students in Saudi Arabia. The findings emphasize the need for targeted educational strategies, standardized curricula, and enhanced AMS training to better prepare future healthcare professionals to combat ABR effectively.
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