ANTIBIOTIC SUBSTANCES 239 



No local or general reactions to these treatments were observed. This 

 material was also administered to 5 human carriers of hemolytic strepto- 

 cocci, 2 of whom were persistent nasal carriers for two months following 

 scarlet fever and the other three convalescent in the third week of this 

 disease. In only one case was an immediate reduction in the number of 

 streptococci obtained ; a striking reduction or complete disappearance of 

 the organisms occurred in the others on the fifth day, after 3 to 4 spray- 

 ings. These observations were said to be sufficiently encouraging to jus- 

 tify the use of the material against carriers harboring streptococci, diph- 

 theria organisms, meningococci, and pneumococci. Injection of 3 to 40 

 mg. tyrothricin into the pleural cavity of rabbits with hemolytic strepto- 

 coccal empyema brought about the sterilization of the pleural cavity and 

 enabled the animal to survive. The injection of 10 mg. of tyrothricin 

 into the pleural cavity of normal rabbits produced certain local tissue re- 

 actions. In excess of 10 mg., adhesions, thickening of the pleura, sterile 

 abscesses, and other disturbances were produced (721). 



The susceptibility of fecal streptococci to tyrothricin varies from 

 strain to strain. Oral administration of the substance may produce in- 

 hibition of the growth of streptococci in the intestines of mice. This 

 inhibition was most readily demonstrated when sulfasuxidine was ad- 

 ministered together with the tyrothricin (761 ). Application of tyrothri- 

 cin to ulcers brought about sterilization and healing of local infections. 

 Application to the mastoid cavity following mastoidectomy also gave 

 favorable results. In staphylococcic infections, resistant strains may de- 

 velop during therapy (722). Certain sulfonamide-resistant strains of 

 iS". fyogenes were eradicated by application of gramicidin (292). 



Tyrothricin and tyrocidine exert a bactericidal effect, and gramicidin 

 is largely bacteriostatic (Figure 29) j the first two are affected by blood 

 and serum, but not the last. In order to be effective against bacteria, 

 the organisms must be in contact with the material (754). Gramicidin 

 is more toxic than tyrocidine, the toxic dose being larger, however, than 

 the dose necessary to kill most gram-positive cocci. Penicillin is one- 

 tenth as toxic as gramicidin (402, 403). 



Both tyrothricin and tyrocidine cause hemolysis of erythrocytes, and 

 both are leukocytolytic, gramicidin being less so. Both tyrothricin and 

 gramicidin cause local and general toxic effects when injected into closed 



