iio8 CHEMOTHERAPY OF BACTERIAL DISEASES 



ESSENTIAL PROPERTIES OF A CHEMICAL AGENT FOR THE CHEMOTHERAPY 

 OF BACTERIAL DISEASES BY SYSTEMIC ADMINISTRATION 



By systemic medication I refer to the administration of compounds by ingestion 

 or injection (subcutaneous, intramuscular, intravenous, etc.) and their subsequent 

 distribution by the blood. This introduces new problems concerning the fate of the 

 compound before it has had an opportunity for attacking the organisms, and the op- 

 portunities and chances for effective disinfection are greatly reduced in comparison 

 with disinfection by direct application. The essential properties of medicaments for 

 this purpose may be summarized as follows: 



1. It must be of sufficiently low toxicity for the body cells to permit of the safe 

 administration of adequate amounts without delayed toxic effects or the production 

 of too violent immediate reactions by incompatibility with the blood. 



2. It must be sufficiently toxic for the bacteria to exert bactericidal and bac- 

 teriostatic effects. For this purpose it must be either sufficiently high in bactericidal 

 activity to be effective in the blood despite high dilution or be a compound convertible 

 in the blood and tissues into a new compound of higher parasitropic activity. 



3. It must not enter too rapidly into physical or chemical union with the con- 

 stituents of the blood or fixed tissues, with the production of inert compounds. 



4. From the standpoint of the treatment of tuberculosis and other bacterial in- 

 fections characterized by the production of pathological exudates and tissues, it must 

 possess the property of penetration sufficient for disinfective purposes by conforming 

 to the physical laws of diffusion or by possessing a chemical affinity for the proteins 

 or other constituents of the organisms according to Ehrlich's conception of parasi- 

 tropic activity. This, however, is not required for the disinfection of the blood and 

 lymph although an affinity between compound and organism must exist. 



5. The compound should not depress immunological processes and especially 

 phagocytosis. On the other hand, it should produce leukocytosis and enhance pha- 

 gocytosis in both the blood and fixed tissues. 



6. In addition to these desirable qualities, the curative activity of a chemo- 

 therapeutic agent or drug may be enhanced if it possess some degree of dynamogenic 

 and chemotactic activity, the properties of exciting hyperemia about lesions with 

 serous and cellular exudation and promoting the proliferation of connective tissue 

 which tends to wall off chronic lesions and gradually aid in their disinfection by 

 cutting off oxygen and food supply and allowing the acids of waste products of 

 bacteria and the products of caseation and liquefying necrosis to check and eventu- 

 ally destroy the organisms. 



BACTERIAL DISEASES IN RELATION TO CHEMOTHERAPY 

 INFLUENCE OF PATHOLOGICAL TISSUE CHANGES 



As would be expected, better results are observed in the chemotherapy of acute 

 than of chronic infections. Probably best results of all are secured in the disinfection 

 of the blood in cases of bacteremia (septicemia). This is true because we have a few 

 drugs like ethylhydrocuprein hydrochlorid, mercurophen, mercurochrome, meta- 

 phen, gentian violet, and acriflavin which may be given in sufficient amounts to raise 

 temporarily the bactericidal titre of the blood for effective sterilization although it 



