Mechanism of Action of Cefuroxime
Cefuroxime is a bactericidal agent that exerts its antibacterial effect by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs), ultimately producing autolysis. 1
Core Mechanism
Cell wall synthesis inhibition: Cefuroxime, characterized by its β-lactam ring structure, binds to various PBPs in the bacterial cell wall, disrupting peptidoglycan synthesis and leading to cell death 2, 1
Bactericidal action: The drug is rapidly bactericidal and induces the formation and subsequent lysis of filamentous bacterial forms over a narrow concentration range 3
Autolytic process: Following PBP binding, cefuroxime triggers bacterial autolysis, which is the self-destruction of the bacterial cell 2
Enhanced β-Lactamase Stability
Increased stability: Cefuroxime demonstrates enhanced stability against certain β-lactamases (both penicillinases and cephalosporinases) produced by gram-negative and gram-positive bacteria, which broadens its spectrum compared to first-generation cephalosporins 1, 3
Spectrum expansion: This β-lactamase stability allows cefuroxime to remain active against many organisms that produce these enzymes and are resistant to earlier cephalosporins, including certain strains of Enterobacter, Klebsiella, and indole-positive Proteus species 3
Resistance Mechanisms
Primary resistance pathways: Bacteria develop resistance to cefuroxime through three main mechanisms: hydrolysis by β-lactamase enzymes, alteration of PBPs (reducing drug binding affinity), and decreased permeability of the bacterial cell wall 1
Clinical limitation: Despite its enhanced stability, cefuroxime's β-lactamase resistance is not absolute in all cases, and certain resistant organisms (such as Pseudomonas aeruginosa, enterococci, and Bacteroides fragilis) remain inherently resistant 3, 4