ENZYMATIC INACTIVATION OF PENICILLINS: AN EMERGING THREAT TO GLOBAL PUBLIC HEALTH

Penicillin antibiotics have been the main-stay armamentarium in the fight against bacterial diseases due to their availability and ease of use. Penicillin resistance has been attributed to modification of penicillin-binding proteins, production of β-lactamases, overexpression of efflux pumps and reduced permeability. In the past 10 years, research was centred on Gram-positive bacteria, particularly Methicillin-Resistant Staphylococcus aureus (MRSA). The key determinant of resistance in MRSA strains is the penicillin-binding protein (PBP2a). Currently, the production of β-lactamases by Gram-negative bacteria has garnered a degree of attention that seems to be rising rapidly. Gram-negative bacteria pose the greatest risk to public health because of the global emergence and spread of metallo-β-lactamases, including Imipenemase (IMP-types), Verona integrin-encoded-metallo-β–lactamases (VIM-types) and New Delhi metallo-β-lactamases (NDM-types). Not only is the increase in resistance of Gram-negative bacteria to beta-lactams faster than in Gram-positive bacteria, but also there are no current and developmental antibiotics active against metallo-β-lactamase-producing Gram-negative bacteria. This review critically examines the current issues in beta-lactamases responsible for penicillins resistance in relation to the current clinically important bacteria pathogens