PHARMACOLOGY OF ANTIBIOTICS — WELCH 407 



From the standpoint of the amounts injected, particularly in the 

 treatment of gram-positive and gram-negative infections, strepto- 

 mycin may be considered to be a drug of low toxity. In the process 

 of the development of streptomycin, the organism Streptomyces 

 griseus produces substances in addition to the antibiotic. Among 

 these substances are histamine and histaminelike substances which 

 in the early impure lots were carried over into the finished drug. 

 These histaminelike substances were responsible for the reports of 

 nausea, vomiting, headache, and flushing of the face following paren- 

 teral use of the drug. Streptomyces griseus not only produces unre- 

 lated chemical compounds that cause untoward reactions on injection, 

 but produces also vitamin B l2 and several other growth-promoting sub- 

 stances during the fermentation process. 



Pyrogenic substances are produced in every batch of streptomycin, 

 or for that matter in every batch of any antibiotic produced by the 

 fermentation process. These pyrogens result from breakdown of the 

 cell of the micro-organism, thereby releasing material that on injec- 

 tion raises the body temperature. The elimination of pyrogens from 

 antibiotics has been a problem since their first use in man. It will be 

 remembered that one of the first side reactions of penicillin was a 

 pyrogenic response in man. Present-day penicillin rarely, if ever, 

 contains pyrogenic substances since they are eliminated in the proc- 

 ess of manufacture. Similarly, these substances are rarely found 

 in present-day commercial lots of streptomycin. The presence of 

 histaminelike substances and pyrogens in dihydrostreptomycin has 

 been rarely noted also since in the case of this drug its clinical use 

 came about only after relatively pure streptomycin was available. 

 Some evidences of renal irritation occasionally accompanied by im- 

 pairment of renal function have been reported, particularly with 

 early lots of streptomycin. Similarly, intramuscular administration 

 of partially purified streptomycin gave rise to some degree of sore- 

 ness and induration at the site of injection. As the purity of the drug 

 increased, however, reports of renal irritation and impairment of renal 

 function decreased in number. It should be emphasized in any case 

 that impairment of renal function ocurred in most instances during 

 therapy in presence of a probable renal disease which had existed 

 before streptomycin treatment was instituted. There appears to be 

 no significant evidence that dihydrostreptomycin produces renal im- 

 pairment with ordinary dosage regimens. 



There is some evidence that streptomycin hydrochloride is more 

 irritating than streptomycin sulfate on intramuscular administration, 

 and this irritation seems to be related to the hydrochloride portion 

 of the molecule. The apparent greater toxicity of the hydrochloride 

 salt of streptomycin has been sufficient to result in the elimination 



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