karbapenem

Carbapenems are a class of β-lactam antibiotics with a distinctive carbapenem nucleus that makes them among the broadest-spectrum agents available. They were developed to resist many β-lactamases that inactivate other penicillins and cephalosporins. Clinically used examples include imipenem, meropenem, ertapenem, and doripenem. Imipenem is co-formulated with cilastatin to inhibit renal dehydropeptidase I, which would otherwise degrade it in the kidney; other carbapenems do not require cilastatin.

Carbapenems act by binding to penicillin-binding proteins, inhibiting peptidoglycan synthesis and producing bactericidal effects. They cover many Gram-positive cocci, a broad range of Gram-negative enteric bacteria, and anaerobes. Ertapenem has limited activity against Pseudomonas aeruginosa and Acinetobacter species, whereas meropenem, doripenem, and imipenem provide stronger activity against Gram-negative pathogens, including some Pseudomonas strains.

They are used for severe or high-risk infections, such as complicated intra-abdominal infections, complicated urinary tract infections, hospital-acquired pneumonia, community-acquired pneumonia (in certain settings), febrile neutropenia, gynecologic infections, and meningitis caused by susceptible organisms. Most carbapenems are given intravenously, with dosages adjusted for renal function. Meropenem penetrates the CSF well and is commonly used for meningitis; ertapenem, by contrast, penetrates less effectively into CSF and is not used for meningitis.

Resistance to carbapenems arises mainly through carbapenemase production (eg, KPC, NDM, VIM, IMP, OXA-48), porin loss, and efflux mechanisms, contributing to carbapenem-resistant Enterobacterales (CRE). To address resistant infections, combinations with newer β-lactamase inhibitors (for example, meropenem-vaborbactam and imipenem-cilastatin-relebactam) are employed in certain settings. Judicious use and antimicrobial stewardship are essential to preserve their effectiveness.