ANTIBIOTICS AS CHEMOTHERAPEUTIC AGENTS 273 



treatment of mice infected intramuscularly with CI. ferjringens placed 

 penicillin first, with tyrothricin and aspergillic acid at the bottom of the 

 list. Penicillin also proved superior to sulfonamides and amino acri- 

 dines in experimental infection with CI. welch'n and CI. oedemat'tens 

 (603). 



The in vivo activity of penicillin against CI. sefticum and other 

 anaerobes, as well as many other bacterial pathogens, is brought out in 

 Table 43. A single subcutaneous treatment of mice with 50 units of 

 penicillin at the time of intramuscular inoculation with CI. welchii 

 protected 98 per cent of the infected animals, and repeated small doses 

 gave as good protection as a single large dose. Delay in the institution 

 of therapy lowered the survival rate, but not appreciably unless the de- 

 lay was over 3 hours. Local lesions were completely healed within 3 

 weeks if penicillin was injected repeatedly into the site of infection. 



The effectiveness of penicillin has also been tested against various 

 other infections in experimental animals, with varying degrees of suc- 

 cess. It was found, for example, that the administration to mice of peni- 

 cillin in relatively large doses after injection with murine typhus rick- 

 ettsiae resulted in marked reduction in mortality, particularly when the 

 initial dosage of the rickettsiae was relatively small (654). Its favorable 

 effect on infections due to the ornithosis virus was also indicated (400). 

 It is also effective in the treatment of leptospirosis in experimental ani- 

 mals (17,547)- 



It has been brought out in recent studies that the effects of different 

 forms of penicillin against the same bacteria are different in the animal 

 body and in the test tube. Penicillin K gave one-quarter to one-eleventh 

 in the blood (injected 0.6 mg./kg.) and persisted in demonstrable 

 levels for only a short time, as compared to F, G, and X. The recovery 

 of K in the urine was 30 to 35 per cent, as compared to 74 to 91 per 

 cent in the case of the other forms. In the treatment of experimental in- 

 fections, K was one-sixth to one-eleventh as active as G, and one-eighth 

 to one-thirteenth as active as X. These data point to the more rapid in- 

 activation of penicillin K in the body, resulting in a lower therapeutic 

 activity (224). 



Although the evidence concerning the effectiveness of different 

 forms of penicillin is still very limited, the conclusions were reached 



