Pathophysiology
Clinical meaning
Antimicrobial resistance (AMR) is a global health emergency driven by selective pressure from antibiotic overuse. Understanding resistance mechanisms guides empiric therapy selection and antimicrobial stewardship. Key resistant organisms: (1) MRSA (methicillin-resistant Staphylococcus aureus): carries the mecA gene encoding PBP2a (penicillin-binding protein 2a), which has extremely low affinity for all beta-lactam antibiotics (penicillins, cephalosporins, carbapenems). Treatment: vancomycin (standard IV therapy; target trough AUC/MIC 400-600), daptomycin (for vancomycin failure), linezolid (for MRSA pneumonia โ vancomycin has poor lung penetration), TMP-SMX or doxycycline (for outpatient skin/soft tissue infections). (2) ESBL-producing gram-negatives (Extended-Spectrum Beta-Lactamase): produce enzymes that hydrolyze penicillins AND cephalosporins (including third-generation cephalosporins like ceftriaxone); most common in E. coli and Klebsiella pneumoniae. Treatment: carbapenems (meropenem, ertapenem) are the drugs of choice. (3) CRE (Carbapenem-Resistant Enterobacteriaceae): produce carbapenemases (KPC, NDM, OXA-48) that hydrolyze ALL beta-lactams including carbapenems โ the last-resort antibiotics. Treatment: ceftazidime-avibactam, meropenem-vaborbactam, or polymyxins (colistin โ nephrotoxic, reserved for pan-resistant organisms). (4) VRE (Vancomycin-Resistant Enterococcus): altered vancomycin target (D-Ala-D-Lac instead of D-Ala-D-Ala). Treatment: linezolid or daptomycin. (5) Clostridioides difficile: not a resistance problem per se but a consequence of antibiotic disruption...