Role of β-Lactamase Inhibitors as Potentiators in Antimicrobial Chemotherapy Targeting Gram-Negative Bacteria

Abstract

Since the discovery of penicillin, β-lactam antibiotics have commonly been used to treat bacterial infections. Unfortunately, at the same time, pathogens can develop resistance to β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems by producing β-lactamases. Therefore, a combination of β-lactam antibiotics with β-lactamase inhibitors has been a promising approach to controlling β-lactam-resistant bacteria. The discovery of novel β-lactamase inhibitors (BLIs) is essential for effectively treating antibiotic-resistant bacterial infections. Therefore, this review discusses the development of innovative inhibitors meant to enhance the activity of β-lactam antibiotics. Specifically, this review describes the classification and characteristics of different classes of β-lactamases and the synergistic mechanisms of β-lactams and BLIs. In addition, we introduce potential sources of compounds for use as novel BLIs. This provides insights into overcoming current challenges in β-lactamase-producing bacteria and designing effective treatment options in combination with BLIs.