JMM Profile: Carbapenems: a broad-spectrum antibiotic

Abstract

Carbapenems are potent members of the β-lactam family that inhibit bacterial cell-wall biosynthesis inhibitors . They are highly effective against Gram-negative and Gram-positive drug-resistant infections . As such, carbapenems are typically reserved as an antibiotic of last resort. The WHO lists meropenem as an essential medicine. Nausea and vomiting are reported in ≤20% of carbapenem recipients, with 1.5% suffering seizures. Enzymatic hydrolysis of the β-lactam ring is the main driver of clinical resistance. These enzymes can be classified as Class A, B and D. Classes A and D are serine β-lactamases, whereas Class B rely on metal-mediated hydrolysis, typically through zinc.

Keywords: antimicrobial resistance; last resort; β-lactams.

Fig. 1.

Structure of commonly administered carbapenems in comparison to the β-lactam penicillin V.

Fig. 2.

The spectrum and mode of action, plus resistance mechanisms, for carbapenems. Carbapenems enter the bacterial envelope (I) and interact with penicillin binding proteins (PBPs) to disrupt cell-wall biosynthesis leading to cell death (II). Porin downregulation prevents drug molecules from reaching the cellular environment (III). Production of low-affinity PBPs can create resistant strains (IV). Enzymatic hydrolysis of the β-lactam ring deactivates the drug compounds (VI). Upregulation of efflux pumps effectively removes the cytotoxic payload from the cell, reducing (or negating) its therapeutic effects (V).

Fig. 3.

The spectrum of action, side effects and route of delivery for carbapenems.