408 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1952 



of this salt of streptomycin from the market, so that at the present 

 time streptomycin sulfate and streptomycin calcium chloride trihydro- 

 cliloride are the only salts available for clinical use. The only dihy- 

 drostreptomycin salt available is the sulfate salt. 



In a general way, the toxicity of dihydrostreptomycin is similar to 

 that of streptomycin, but this toxicity should be compared with rela- 

 tively pure streptomycin only since dihydrostreptomycin is produced 

 from relatively pure lots of streptomycin. The neurotoxicity of 

 dihydrostreptomycin when tested in animals is approximately one-half 

 that of streptomycin. The lower neurotoxicity of dihydrostrepto- 

 mycin has been shown clinically in man by several investigators. A 

 delayed neurotoxic effect of dihydrostreptomycin on the auditory 

 system of patients evidenced by delayed deafness several weeks after 

 treatment had been discontinued has also been reported. There is 

 some question as to whether this "delayed deafness" is in reality 

 delayed or whether it is actually a slow progressive increase in deafness. 

 Studies are now in progress in an attempt to determine the facts 

 in this unexpected toxic reaction in a relatively large group of pa- 

 tients. 3 In any case, careful investigation has failed to demonstrate 

 a greater neurotoxicity of dihydrostreptomycin over streptomycin on 

 the auditory system in cats. Indeed, in these animals dihydrostrepto- 

 mycin appears to affect the auditory and vestibular systems to a lesser 

 degree than does streptomycin. 



As with the other antibiotic drugs, streptomycin causes skin erup- 

 tions during the course of treatment. These are relatively common 

 but usually are transient and not considered to be an indication for 

 the discontinuance of therapy. Although the impurities present in the 

 early crude preparations of streptomycin may have been responsible 

 for some of the skin reactions observed, the drug is capable inherently 

 of producing sensitivity. Skin reactions occur in about 4 percent of 

 the cases treated. Occasionally severe urticaria complicating strepto- 

 mycin therapy occurs, and two deaths have been reported from derma- 

 titis and stomatitis during streptomycin therapy. Contact dermati- 

 tis is caused by streptomycin more often than by penicillin. Not infre- 

 quently, individuals in industrial plants handling the drug become 

 sensitive to it. In addition, nurses having intimate contact with the 

 drug often show epidermal sensitization to streptomycin. 



Absorption and excretion. — Following injection, streptomycin is 

 readily absorbed and excreted. The usual method of administration 

 is by the intramuscular route, and although intravenous administra- 



*This study has now been completed (February 1953) and has shown dihydrostrepto- 

 mycin to have a higher toxicity for tbe auditory branch of the eighth nerve than strep- 

 tomycin, while the reverse is true for the vestibular branch of this nerve. Recent studies 

 bave also shown a marked reduction in toxicity for both branches of the eighth nerve 

 through use of a mixture containing equal parts of these drugs. 



