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Cephalosporins 1945–1986

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In 1945, after penicillin had been introduced into medicine, an antibiotic-producing species of Cephalosporium was isolated from a sewage outfall in Sardinia. Four years later in Oxford, this organism was found to produce several antibiotics, one of which was a penicillin with a new side-chain, penicillin N. During a chemical study in 1953, this penicillin was shown to be contaminated with a second substance, cephalosporin C, which contained a β-lactam ring but was resistant to hydrolysis by a penicillinase (β-lactamase). At that time, penicillinase-producing Staphylococci were causing a serious problem in hospitals.

The isolation of the nucleus of cephalosporin C (7-ACA) enabled pharmaceutical manufacturers to produce many thousands of cephalosporins, some of which have been effective in the treatment of serious infections by a number of Gram-positive and Gram-negative bacteria. The cephalosporins, like the newer penicillins, have a very low toxicity and have greatly extended the range of chemotherapy. New, sensitive screening methods have revealed further families of clinically useful substances that contain a reactive β-lactam ring.

Genetic engineering has now begun to throw light on the nature of the enzymes that are involved in the biosynthesis of penicillins and cephalosporins, and x-ray crystallography may soon provide detailed 3-dimensional pictures of some of the bacterial enzymes with which the active β -lactam ring reacts. Rational approaches to the production and design of new and potentially useful compounds may then be within sight.

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  1. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, England

    E. P. Abraham

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Abraham, E.P. Cephalosporins 1945–1986. Drugs 34 (Suppl 2), 1–14 (1987). https://doi.org/10.2165/00003495-198700342-00003

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