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Class C AmpC β-lactamases are clinically significant enzymes produced by various Gram-negative bacteria, including the SPACE organisms (Serratia, Pseudomonas, Acinetobacter, Citrobacter, and Enterobacter), which mediate resistance to a broad spectrum of β-lactam antibiotics [1][2]. These enzymes are serine-hydrolases that efficiently degrade penicillins, cephalosporins, and monobactams, but are notably not inhibited by first-generation β-lactamase inhibitors like clavulanic acid [3]. The expression of AmpC can be chromosomal and inducible or plasmid-mediated, with the latter facilitating rapid spread between bacterial species [4]. A major clinical concern is derepression, where mutations lead to permanent high-level enzyme production, rendering even advanced cephalosporins ineffective during the course of therapy [3][5]. To combat this, newer diazabicyclooctane and boronate-based inhibitors, such as avibactam and vaborbactam, have been developed to specifically target and neutralize Class C enzymes [6]. Monitoring for AmpC-mediated resistance is essential for selecting appropriate carbapenem-sparing regimens and preventing the escalation of antimicrobial resistance [1][4].
Inhibition of the enzyme's catalytic activity through covalent or non-covalent binding to the serine active site, preventing the hydrolysis of co-administered beta-lactam antibiotics [3][6].
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