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The nature of penicillin, mode of action, and principles of penicillin therapy.

Penicillin was first produced on a large scale by fermenting various strains of Penicillium notatum, from which several compounds and derivatives were extracted, i.e. penicillin F, G, X, and K (Bacharach & Hems, 1946). In the effort to develop pure preparations, commercial penicillin came to contain more N-heptylpenicillin (K fraction) and less benzylpenicillin (G fraction). Consequently, the results obtained in treating syphilis became temporarily less good (Moore, 1946) since the other fractions proved less antitreponemal than benzylpenicillin G (Carpenter et al., 1946; Arnold et al., 1947; Eagle & Fleischman, 1948). In syphilis therapy, therefore, benzylpenicillin G became the preparation of choice. It was soon to become commercially available in a nearly pure form (Willcox, 1947). In 1948, the penicillin molecule was shown to consist of a nucleus, 6-aminopenicillanic acid (Brotzu, 1948), and a side chain linked to the amino group of the nucleus. The antibiotic effect was found to depend on the nature of the side chain acid (Chain, 1964). The addition of phenylacetic acid resulted in benzylpenicillin G. The penicillin nucleus contains a fused thiazolidine ,B-lactam ring, on the integrity of which depends the acid stability of penicillin. The penicillin nucleus is capable of forming salts. Among these the procaine penicillin salt of penicillin G (Buckwalter & Dickison, 1948) and its N,N'-dibenzylethylenediamine salt (DBED or benzathine penicillin G) (Szabo et al., 1951) have particular therapeutic value-e.g., in the treponematoses (syphilis, yaws, and pinta). The characteristics of the penicillin molecule are shown in Fig. 1, while Fig. 2 illustrates the structure of the related cephalosporins. In the early years of penicillin production, attempts were made to manufacture different penicillins