Extended-spectrum cephalosporins and related beta-lactams.

Abstract

One of the truly remarkable developments in contemporary science is the discovery, synthesis, and clinical application of the β-lactam antibiotics. This story began in 1928 when Fleming observed the lytic properties of the mould, Penicillium, on cultures of staphylococci. Fully 12 years elapsed, however, until in 1940 the group of workers at Oxford, headed by Chain, Florey and Abraham appreciated and demonstrated the chemotherapeutic properties of penicillin. Following their discovery, a search for other antibiotic-producing organisms was begun on a world-wide basis. In 1945, Professor Giuseppe Brotzu in Sardinia began his work. He examined the microbial flora of sea water near a sewage outlet at Cagliari, Sardinia. He had supposed that the process of self-purification of the water might be due to the effect of bacterial antagonism, with substances produced by certain organisms inhibiting the growth of other bacteria. His early work was fruitful, and he isolated a fungus which he concluded was similar to Cephalosporium acremoniwn . When grown on solid medium, this fungus secreted material that inhibited the growth of a number of Gram-positive and Gram-negative bacteria. This led to a series of studies which resulted in the isolation of a strain of fungus that produced considerable amounts of antibiotic material when grown in broth. Subsequently, both culture filtrates and active concentrates from the Cephalosporium species were tested in patients in Sardinia by injecting the filtrates directly into staphylococcal and streptococcal cutaneous lesions. In addition, the concentrates were administered both intravenously and intramuscularly to patients with typhoid fever, paratyphoid infections, and brucellosis. Brotzu believed that his clinical results were encouraging and published an account of his work in 1948. Because of lack of resources and failure to gain support for his work in Italy, Brotzu sent a culture of his organism to Oxford in 1948, but not until nearly 20 years later did the cephalosporin antibiotics come into widespread clinical use.