Pathophysiology
Clinical meaning
Antibiotic stewardship at the clinician prescriptive level requires deep understanding of resistance mechanisms, pharmacokinetic/pharmacodynamic (PK/PD) optimization, and evidence-based prescribing. Key resistance mechanisms include: ESBL-producing Enterobacterales (plasmid-mediated CTX-M enzymes hydrolyzing third-generation cephalosporins), carbapenem-resistant Enterobacterales (CRE via KPC, NDM, OXA-48 enzymes), MRSA (mecA gene encoding PBP2a with reduced beta-lactam affinity), and vancomycin-resistant Enterococcus (vanA/vanB gene clusters). PK/PD targets drive dosing: time-dependent antibiotics (beta-lactams) target fT>MIC >40-70%, concentration-dependent antibiotics (aminoglycosides) target Cmax/MIC >10, and AUC-dependent antibiotics (vancomycin, fluoroquinolones) target AUC/MIC ratios. The clinician must select empiric therapy based on local antibiograms, optimize dosing using PK/PD principles, de-escalate based on culture data, determine appropriate duration, and implement stewardship quality metrics.