Structure-Activity Relations of New β-Lactam Compounds and in Vitro Activity Against Common Bacteria

Abstract

Molecular modifications of the penicillin and cephalosporin nuclei have made it possible to create molecules that more readily cross the outer membranes of bacterial cells, resist destruction by p-lactamases, or bind more avidly to receptors involved in bacterial cell wall synthesis. Penicillin compounds, such as the penicillin mecillinam, owe their activity against gram-negative bacilli to their affinity for a specific penicillin-binding protein (PBP), PBP2. Agents such as apalcillin, azlocillin, mezlocillin, and piperacillin, which are ureido derivatives of ampicillin, are active against many organisms even though they are not p-lactamase-stable because they pass readily through the outer membrane and have a high affinity for PBPs 1 and 3. The methoxyimino cephalosporins, cefotaxime, ceftizoxime, cefmenoxime, and ceftriaxone combine high resistance to hydrolysis by both plasmid and chromosomal p-lactamases with a great affinity for PBPs. The presence of an acid function on the acyl side chain confers both resistance to the cephalosporinases of Pseudomonas and activity against various species to such different compounds as cefsulodin, ceftazidime, and moxalactam. In spite of these changes in structure, which have improved antibacterial activity, organisms resistant to all of the new and novel agents have already been found.