🦠 Since the introduction of penicillins in the 1940s, β-lactam antibiotics have been a cornerstone of modern medicine. However, bacteria quickly fought back by producing β-lactamase enzymes that degrade these antibiotics before they can exert their effect. To overcome this, β-lactamase inhibitors (BLIs) were developed to be co-administered with β-lactam antibiotics, protecting them by irreversibly binding and inactivating β-lactamase enzymes — thereby restoring the antibiotics’ ability to target penicillin-binding proteins (PBPs) and kill the bacteria.

⚙️The discovery of the first BLI, clavulanic acid from Streptomyces clavuligerus, was a key breakthrough. Most people have been prescribed Augmentin^®, the combination of amoxicillin and clavulanic acid that has been in use since 1981. This was followed by synthetic inhibitors like sulbactam and tazobactam, introduced in the mid-1980s and early 1990s respectively. More recently, two new classes of non-β-lactam inhibitors, diazabicyclooctanes (DBOs) and boronates, have been developed.

💡Fast forward to the approval in February 2024 of a new BLI/β-lactam combination: enmetazobactam + cefepime (marketed as Exblifep^®) has now been approved in the USA, Europe, and India for the treatment of complicated urinary tract infections (cUTIs). The enmetazobactam story began in India, where researchers at Orchid Research Laboratories identified that adding a methyl group to the triazole ring of tazobactam created a zwitterionic BLI. This small chemical change dramatically improved bacterial penetration and pharmacokinetic properties. Allecra Therapeutics (headquartered in Germany with operations in France) led the clinical development.

🌟 Enmetazobactam is a great example of how thoughtful chemical modifications, combined with an understanding of resistance mechanisms, can deliver clinical impact.

#AMR #IndiaInnovation #Antibiotics #DrugDevelopment #InfectiousDiseases #Innovation