410 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1952 



presence of renal damage, markedly different results may be obtained. 

 The renal clearance in man is approximately 70 percent of the simul- 

 taneously determined glomerular nitration rate. In the dog practi- 

 cally all the streptomycin administered can be accounted for by ex- 

 cretion in the urine. In man, however, a considerable amount of the 

 drug is frequently not found in the urine. 



Several daily injections of streptomycin parenterally usually pro- 

 duce an equilibrium between the quantities administered and the 

 amounts excreted. In the individual with normal renal clearance, a 

 balance is reached rather rapidly and, as long as it remains normal, 

 may be maintained for considerable periods of time. In the presence 

 of renal damage, however, the blood concentrations may rise very rap- 

 idly. In any case, it is advisable and in some instances essential that 

 the concentration of streptomycin in the serum be followed by labora- 

 tory assay. As has been indicated previously, the development of neu- 

 rotoxic symptoms is related to the height of the blood concentration 

 and duration of treatment. High concentrations of streptomycin in 

 the serum for prolonged periods of time may result in evidences of 

 neurotoxicity. 



BACITRACIN 



Although the bacitracin originally produced was made by the sur- 

 face-culture method, the present material is produced by deep-tank 

 fermentation. Production of this drug in the United States is largely 

 by one manufacturer, but approximately five have produced small 

 quantities during the past two years. There appear to be no dif- 

 ferences in the antibacterial activity of that produced by surface cul- 

 ture and that produced by deep tank. 



There is little doubt concerning the toxicity of the bacitracin now 

 commercially available. It is produced fairly uniformly at a potency 

 of 40 units per mg., and this is approximately 60 percent pure. Fur- 

 ther purification beyond 45 units per mg. results in some instability 

 which becomes pronounced at potencies much in excess of 45 units 

 per mg. Animal tests invariably show the drug at these potencies 

 to be nephrotoxic, producing damage to the renal tubules of mice 

 and rats. Kidney damage is observed in dogs given 5,000 units per 

 kg. twice daily for 3 days. 



In man, bacitracin has been shown to produce local pain and injury 

 on intramuscular injection. At the site of injection, petechiae of the 

 skin and macular rashes have been observed. Some nausea and 

 vomiting have also been noted, and occasionally tinnitus occurs. Of 

 more importance, however, is the appearance of albuminuria and an 

 increase in blood urea nitrogen in some patients. Most patients treated 

 with bacitracin show some nephrotoxic phenomena. These vary in 

 degree with different lots of bacitracin. The nephrotoxicity is re- 



