Dicloxacillin covalently binds penicillin-binding proteins (PBPs), halting the transpeptidation step of peptidoglycan synthesis and leading to bactericidal cell wall disruption. Its bulky side chain protects the beta-lactam ring from hydrolysis by staphylococcal penicillinases, making it effective when aminopenicillins fail. Time above the MIC drives activity; therefore, q6h dosing on an empty stomach is critical to maintain therapeutic levels.