Pharmacology of Antibiotics 1 



By Henry Welch 



Director, Division of Antibiotics 



Food and Drug Administration 



U. S. Department of Health, Education, and Welfare 



The impetus given to the search for new antibiotics after the dis- 

 covery of tyrothricin by Dubos in 1939 and the development of peni- 

 cillin during World War II has resulted in the reporting of literally 

 hundreds of new and untried antimicrobial substances. There has 

 been compiled recently a dictionary of these substances in which are 

 listed some thousands of antibiotics and, because of the large number 

 of screening programs in progress, their number is increasing. It is 

 significant, however, that of these thousands of antimicrobial sub- 

 stances less than ten have been found to be useful in the treatment 

 of human or animal diseases. 



The pharmacological study of a new antibiotic is usually not a 

 simple one, particularly if the agent is impure. It will be remembered 

 that both penicillin and streptomycin when first used clinically were 

 relatively crude drugs, much more so in the case of penicillin than 

 streptomycin. As a result, some of the toxicity first attributed to 

 penicillin, such as irritation on injection and damage to nerve tissue, 

 could not be immediately assigned to the pure crystalline substance 

 per se. The purification of penicillin revealed that intramuscular 

 irritation was related to purity while toxicity for nerve tissue was in- 

 herent in the drug itself. At the present time it is difficult, if not 

 impossible, to determine whether the nephrotoxicity of bacitracin 

 and neomycin is due to impurities or whether it is a quality inherent 

 in the drugs themselves, though it appears that the latter is the case. 

 The "broad spectrum" antibiotics — aureomycin, chloramphenicol, and 

 terramycin — are crystalline drugs which contain few if any impuri- 

 ties. Thus any toxicity demonstrated for them can be attributed to 

 the drugs themselves. It is perhaps unfortunate that, because of the 

 need, it was necessary to use penicillin and streptomycin prior to their 

 purification to the crystalline state. However, the progress made in 



1 Reprinted by permission from the Journal of the History of Medicine and Allied 

 Sciences, vol. 3, 1951. 



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