The Impact of Inappropriate Use Patterns on Sub-Lethal Antibiotic Exposure: A Multivariate Analysis on the Selection Risk of Resistant Mutants

Background: Antimicrobial resistance (AMR) is an evolutionary crisis accelerated by inappropriate antibiotic use. While awareness studies often focus on descriptive knowledge, evidence-based predictive models identifying how cognitive deficits trigger treatment non-adherence are lacking. This study analyzed predictors of antibiotic non-adherence among university students using a multivariate behavioral-microbiological approach. Methods: A cross-sectional KAP (Knowledge, Attitude, and Practice) survey was conducted with 1044 students (Nursing: n = 620; non-healthcare: n = 424) in Northern Cyprus. A validated questionnaire assessed antimicrobial awareness. Multivariate logistic regression identified independent predictors (Adjusted Odds Ratio AOR) of treatment non-adherence. Results: Nursing students achieved significantly higher median scores in knowledge (9 vs. 7), attitude (10 vs. 8), and practice (9 vs. 7) compared to non-healthcare students (p < 0.001). Within the nursing cohort, a significant linear progression in KAP scores occurred from the 1st to 4th academic years (p < 0.05). The strongest independent predictor of antimicrobial non-adherence was inappropriate attitude (AOR: 2.100; 95% CI: 1.586–2.780; p < 0.001), followed by inadequate knowledge (AOR: 1.536; 95% CI: 1.160–2.033; p = 0.003). Conversely, nursing education was a significant protective factor (AOR: 0.669; p = 0.005). Conclusions: Antibiotic non-adherence is a complex psychological behavior management issue rather than merely an information deficit. Incorrect attitudes primarily drive sub-lethal dose exposure, theoretically increasing the epidemiological risk associated with resistant mutant selection. Future antimicrobial stewardship (AMS) programs must transcend traditional educational models and incorporate behavioral economics principles, such as digital nudging, to modify inappropriate attitudes.