ANTIBIOTIC SUBSTANCES 237 



are inactive in vitro can, when given by the oral route, become highly 

 active against hemolytic streptococci (599, 600). 



Production. Because of the limited amounts of penicillin available 

 at the present time, many attempts have been made by physicians and 

 hospitals to grow P. notatum on a suitable medium and use the crude 

 culture filtrate for the treatment of wounds and infections. Since such 

 cultures cannot be standardized and their activity cannot always be de- 

 termined and since unforeseen toxic substances may be produced by cer- 

 tain contaminants in the culture, this practice should not be encouraged, 

 unless carefully supervised by properly qualified bacteriologists. 



The production of penicillin-destroying enzymes by bacteria and 

 fungi (4, 379, 516) can be utilized for the purpose of testing the steril- 

 ity of penicillin preparations. The penicillin, which would otherwise 

 cause inhibition of growth of the contaminating organism in the test 

 medium, is destroyed by the enzyme previous to the test. No apparent 

 relation was said ( lOOO) to exist between the resistance of an organism 

 to penicillin and its ability to produce penicillinase, a fact not generally 

 accepted (73-75). The mode of action of the enzyme is still not clearly 

 understood, although there is apparently an increase in the number of 

 carboxyl groups, as measured by ^H change ( lOOo). 



Clavacin {Patulin) 



The treatment of common colds that were prevalent in an English 

 naval establishment by the use of clavacin in the form of nasal sprays or 

 snuffed up by hand gave 57 per cent complete recovery in 48 hours, as 

 compared with 9.4 per cent for the controls} no ill effects were observed 

 (713). These results were not confirmed, however, the conclusion hav- 

 ing been reached that, compared with the natural evolution of the dis- 

 ease, patulin has no demonstrable effect on the course of a cold (847a). 

 This substance also proved to be unsatisfactory for the treatmnt of bo- 

 vine mastitis by udder infusion (681 a). 



Tyrothricin 



Dubos (193) reported that 0.002 mg. of gramicidin, one of the two 

 chemical constituents of tyrothricin, when injected intraperitoneally 

 into white mice, exerted a therapeutic action against experimental peri- 



