Use and control of cephalosporins.

It is now over 20 years since Professor Brotzu recovered the mould Cephalosporium acremonium from Sardinian sewage and found that it produced antibiotic material. Figure 1 represents a simplified cephalosporin family tree. The first antibiotic to be isolated from the mould was cephalosporin N, an acyl derivative of 6-aminopenicillanic acid, susceptible to the action of stapylococcal penicillinase and much less active against Gram-positive bacteria than benzyl penicillin. Cephalosporin P consists of one major component and at least four minor components: its major component is a steroid related chemically to, but considerably less active than, fusidic acid. The most important antibiotic elaborated by the cephalosporium mould is cephalosporin C, but it is only produced in minute quantities. It is from cephalosporin C that the semi-synthetic cephalosporins have been derived. Several hundred analogues have been produced by substitution of different chemical groups at the 7 and 3 position (R1 and R2 in the diagram) of the cephalosporin nucleus and have been investigated for antimicrobial activity. Four cephalosporins have been extensively studied in various parts of the world-cephaloridine, cephalothin, cephalexin, and cephaloglycine-and of these the first three drugs are now available commercially in Britain and it is with them that this paper is concerned. Cephaloridine has been available since 1964 and cephalothin and cephalexin much more recently.