The Cephalosporins

In recent years the cephalosporin antibiotics have been used with increasing success in the fight against bacterial infection. This success is the result of considerable endeavour and perseverance, especially by Abraham and Newton at Oxford in the early years after the discovery of the Cephalosporium acremonium mould near a sewage outlet in Sardinia. It was 10 years before the first cephalosporin, cephalosporin C, was isolated, and almost another 10 years passed before cephalosporins became available for successful clinical use. Since then the cephalosporin family has increased rapidly in size and potency, and it now provides us with a whole range of powerful and clinically successful antibiotics. One key reason for this success is the highly selective action of the cephalosporins, which kill bacteria by inhibiting target proteins essential to the synthesis of bacterial cell walls; these bacterial targets are not present in man. A study of the structure and synthesis of bacterial cell walls indicates how the cephalosporins act at a molecular level and provides some clues for the design of improved cephalosporins. The development of the cephalosporins has also been closely linked to the study of bacterial resistance, and this interrelationship will be explored.