Antibiotic stewardship encompasses systematic strategies to optimize antimicrobial use, improve patient outcomes, and reduce the emergence of resistant organisms. Understanding resistance mechanisms at the molecular level is essential for RN-level clinical decision-making. Beta-lactamase production is the most common resistance mechanism in gram-negative bacteria. These enzymes hydrolyze the beta-lactam ring, rendering penicillins, cephalosporins, and carbapenems inactive. Extended-spectrum beta-lactamases (ESBLs), primarily CTX-M enzymes encoded on mobile plasmids, confer resistance to third-generation cephalosporins (ceftriaxone, ceftazidime) and are treated with carbapenems. Carbapenem-resistant Enterobacterales (CRE) produce carbapenemases (KPC in K. pneumoniae, NDM-1 in E. coli) that destroy even last-resort carbapenems — these infections carry 40-50% mortality and require ceftazidime-avibactam or polymyxin-based regimens. Efflux pumps are transmembrane protein complexes that actively transport antibiotics out of the bacterial cell before they can reach their intracellular targets. Multiple families exist: MexAB-OprM in Pseudomonas aeruginosa confers resistance to beta-lactams, fluoroquinolones, and chloramphenicol simultaneously. Efflux pump overexpression is a major contributor to multidrug resistance (MDR), as a single pump system can expel multiple antibiotic classes. Target modification alters the antibiotic's binding site, reducing drug affinity. The mecA gene in MRSA...