β-Lactam antibiotics with novel nuclei

Abstract

Since the isolation of the penicillin nucleus a huge number of semisynthetic penams and cephems have been generated by manipulation of the side chain at the 6 position of 6 amino penicillanic acid and at the 7 and 3 positions of 7 amino-cephalosporanic acid. The objectives of this manipulation have been to secure improvements over the parent compounds in four properties: (1) degree of intrinsic antibacterial activity; (2) extension of antibacterial range to include organisms resistant to the parent compound — an objective that has centred to a substantial extent on Pseudomonas aeruginosa, but has extended to include other naturally resistant Gram-negative rods such as Enterobacter, Serratia, indole-positive Proteus and anaerobic bacteria; (3) stability to a wide range of β-lactamases, the major cause of resistance in an increasing variety of organisms to earlier β-lactams; and (4) improvement in pharmacokinetic behaviour.