Biochemical exploration of β-lactamase inhibitors.

Abstract

The alarming rise of microbial resistance to antibiotics has severely limited the efficacy of current treatment options. The prevalence of β-lactamase enzymes is a significant contributor to the emergence of antibiotic resistance. There are four classes of β-lactamases: A, B, C, and D. Class B is the metallo-β-lactamase, while the rest are serine β-lactamases. The clinical use of β-lactamase inhibitors began as an attempt to combat β-lactamase-mediated resistance. Although β-lactamase inhibitors alone are ineffective against bacteria, research has shown that combining inhibitors with antibiotics is a safe and effective treatment that not only prevents β-lactamase formation but also broadens the range of activity. These inhibitors may cause either temporary or permanent inhibition. The development of new β-lactamase inhibitors will be a primary focus of future research. This study discusses recent advances in our knowledge of the biochemistry behind β-lactam breakdown, with special emphasis on the mechanism of inhibitors for β-lactam complexes with β-lactamase. The study also focuses on the pharmacokinetic and pharmacodynamic properties of all inhibitors and then applies them in clinical settings. Our analysis and discussion of the challenges that exist in designing inhibitors might help pharmaceutical researchers address root issues and develop more effective inhibitors.