Key Concepts
Introduction
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...