Beta-Lactam Antibiotics and Resistance Mechanisms

Classification and Mechanism of Action

Carbapenems, such as imipenem, meropenem, and ertapenem, represent the broadest spectrum beta-lactams with exceptional stability against most beta-lactamases, according to Clinical Microbiology and Infection 1
All beta-lactams share a common mechanism: they inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) at the active-site serine, forming a covalent complex that prevents peptidoglycan cross-linking, as reported in Clinical Microbiology and Infection 1
Monobactams, such as aztreonam, have a unique monocyclic structure and activity limited to gram-negative bacteria, as stated in the Journal of Allergy and Clinical Immunology 2

Class A beta-lactamases, including extended-spectrum beta-lactamases (ESBLs) and carbapenemases like KPC, account for 47.4% of meropenem-resistant Enterobacterales globally, according to Praxis Medical Insights 3
Class B beta-lactamases, including metallo-beta-lactamases (MBLs) like NDM, VIM, and IMP, represent 20.6% of carbapenem-resistant isolates, as reported in Praxis Medical Insights 3
Class D beta-lactamases, including oxacillinases like OXA-48, account for approximately 19% of carbapenemases in Enterobacterales, according to Praxis Medical Insights 3

Klebsiella pneumoniae is intrinsically resistant to ampicillin and aminopenicillins and frequently acquires ESBLs conferring resistance to cephalosporins and aztreonam, as stated in Praxis Medical Insights 3
For KPC-producing organisms, first-line treatment is ceftazidime/avibactam or meropenem/vaborbactam, as these combinations effectively inhibit Class A carbapenemases, according to Praxis Medical Insights 4
For MBL-producing organisms, the required regimen is ceftazidime/avibactam PLUS aztreonam or cefiderocol as an alternative, as reported in Praxis Medical Insights 4