Klebsiella pneumoniae carbapenemase-3 (KPC-3) (KPC-3)

Klebsiella pneumoniae carbapenemase-3 (KPC-3) is a plasmid-encoded Ambler Class A serine beta-lactamase that confers high-level resistance to a broad spectrum of beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems [1.3.1, 1.3.5]. Originally identified in Klebsiella pneumoniae, it has since spread to other Enterobacteriaceae and Gram-negative pathogens via mobile genetic elements [1.3.4, 1.5.1]. The enzyme utilizes a catalytic serine residue to hydrolyze the beta-lactam ring, effectively neutralizing the antibiotic's ability to inhibit bacterial cell wall synthesis [1.3.3, 1.4.3]. KPC-3 is a critical target in the management of carbapenem-resistant Enterobacteriaceae (CRE) infections, which are associated with significant morbidity and mortality [1.3.4, 1.5.3]. Therapeutic interventions typically involve the use of beta-lactamase inhibitors such as avibactam, vaborbactam, or relebactam, which bind to and inhibit KPC-3, thereby restoring the activity of co-administered antibiotics like ceftazidime or meropenem [1.4.2, 1.4.4]. However, the emergence of KPC-3 variants that exhibit resistance to these newer inhibitor combinations represents a major clinical challenge and underscores the need for continuous antibiotic stewardship and drug development [1.1.2, 1.5.1].

Other names

KPC-3blaKPC-3Klebsiella pneumoniae carbapenemase 3Class A carbapenemase KPC-3Serine carbapenemase KPC-3

Inhibition of the enzyme's catalytic serine residue by beta-lactamase inhibitors (BLIs) such as avibactam, vaborbactam, or relebactam, which prevents the hydrolysis of co-administered beta-lactam antibiotics by forming a stable or reversible covalent complex with the active site [1.4.1, 1.4.2].