Promising Future of Novel Beta-Lactam Antibiotics Against Bacterial Resistance

Saeed M Tayeb,1 Jaser A Alharbi,1 Bushra B Alattas,1 Dana M Alotaibi,1 Nawaf M Althibaiti,1 Jaser F Alharbi,1 Ahmad E SafirAldeen,1 Ibrahim R Alqurashi,1 Saad M Wali2 1Pharmaceutical Sciences Department, College of Pharmacy, Umm Al-Qura University, Makkah, 24381, Saudi Arabia; 2Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, 24342, Saudi ArabiaCorrespondence: Saad M Wali, Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia, Tel +966543800090, Email [email protected]: Antimicrobial resistance is a growing global concern that compromises the efficacy of antibiotics, particularly due to the misuse and overuse of these agents. Beta-lactam antibiotics, widely used for their broad-spectrum activity, are increasingly threatened by bacterial resistance mechanisms. Recent studies showed that resistant Gram-negative bacteria cause many hospital infections, which makes the search for new treatments very urgent.Objective: This review explores recent advancements in the development of novel beta-lactam antibiotics, including new drug combinations and structural modifications designed to overcome beta-lactamase degradation and effectively target mutated penicillin-binding proteins (PBPs).Literature Review: One of the main resistance mechanisms in Gram-negative bacteria is the production of beta-lactamases, which break the beta-lactam ring and stop the drug from working. New ideas include adding more than one beta-lactam ring in the drug, combining with strong beta-lactamase inhibitors, and making hybrid structures. These strategies have shown promising results in preclinical evaluations.Conclusion: Novel beta-lactam antibiotics demonstrate significant potential in combating resistant bacterial strains. Future directions should emphasize large-scale in vivo validation, the incorporation of novel β-lactamase inhibitors, and the development of advanced drug delivery systems. Integration of these strategies may enhance the clinical applicability of β-lactams and provide sustainable solutions to address the global burden of antimicrobial resistance.Keywords: beta-lactamase, Gram-negative bacteria, Gram-positive bacteria, penicillin-binding proteins, cross-resistance, polymer inclusion nano-complex, beta-lactam antibiotics