46 RAPER 



and the parasitic amoebae. It is generally less toxic than Chloromycetin, and 

 it possesses great penetrating powers which commend it for use in deep tissue 

 infections. 



The third of the broad-spectrum antibiotics, terramycin (oxy tetracycline), 

 was discovered by a team of research microbiologists at the Charles Pfizer 

 Company in 1950, and it is manufactured on a large scale by that pharma- 

 ceutical firm. In general, terramycin is used for the same types of therapy 

 as aureomycin. Like that drug, it is used in the treatment of amoebic dysen- 

 tery, and it is reported to be effective in the treatment of African sleeping 

 sickness, caused by another type of protozoa, the trypanosomes. Terramycin 

 is obtained from 5. rimosus. 



The fourth broad-spectrum antibiotic, ilotycin (erythromycin), was dis- 

 covered by J. M. McGuire and coworkers in the Research Laboratories of 

 the Eli Lilly Company and is derived from S. erythreus. This antibiotic is 

 currently produced in substantial amounts by this firm and by two additional 

 ones, who market the drug under different trade names. Erythromycin finds 

 its greatest usefulness in combating infections caused by gram-positive patho- 

 gens that have developed resistance to the earlier-discovered antibiotics. 



The fifth broad-spectrum antibiotic, tetracycline, is very closely related 

 to aureomycin and terramycin, differing from these in the absence of a chlo- 

 rine atom and an OH group, respectively. This antibiotic can be produced 

 by chemical means wherein the chlorine is removed from aureomycin by 

 simultaneous dechlorination and hydrogenation, or it can be produced by 

 conducting a primary fermentation using a strain of Streptomyces different 

 from those employed to produce aureomycin or terramycin. The drug is now 

 being produced in large amounts by each of these processes. Tetracycline 

 seems to be generally the most useful and the least toxic of the five broad- 

 spectrum drugs. It possesses curative properties equal to aureomycin and 

 terramycin coupled with fewer disagreeable side reactions, hence is preferred 

 for many types of therapy. It is currently produced in amounts almost equal 

 to that of the other four broad-spectrum drugs combined. The total pro- 

 duction of all broad-spectrum antibiotics in 1955 was somewhat in excess of 

 450,000 pounds. The net value of these drugs (produced and marketed by 

 single companies, except for tetracycline and erythromycin) in the same 

 year amounted to approximately $195 million. The tetracycline produced 

 in that year alone was marketed for $95 million. 



Additional to these major drugs obtained from species of Streptomyces, 

 two additional antibiotics of actinomycetous origin should be mentioned. 

 Neomycin, produced by S. jradiae and discovered by Waksman, finds im- 

 portant uses in the preparation of ointments for topical use and as a pre- 

 operative drug in surgery. It is often combined with other antibiotics. The 

 other, nystatin, discovered by Hazen and Brown and produced by S. noursei, 

 exhibits much desired fungistatic properties. One of the drawbacks of the 



