iii6 CHEMOTHERAPY OF BACTERIAL DISEASES 



DYE FASTNESS OF BACTERIA IN RELATION TO CHEMOTHERAPY 



Of considerable interest in relation to the employment of dyes in the chemo- 

 therapy of bacterial infections is the question of whether or not some species may 

 acquire or naturally possess a resistance or fastness to the anilin dyes, Simon and 

 Wood believe that some members belonging to dye-susceptible groups of organisms 

 exist in nature which are not inhibited by the dyes in question, and that dye sus- 

 ceptibility may be overcome to a greater or less extent by adaptation or the acquisi- 

 tion of fastness (resistance). 



Various spirochetes and trypanosomes, however, have been rendered resistant to 

 anilin dyes, arsenicals, and other substances, and my experience indicates that differ- 

 ent strains of staphylococci, streptococci, and colon and typhoid bacilli may exhibit 

 slightly varying natural resistance to the anilin dyes. I have not tried to render any 

 one strain particularly resistant or fast to a particular dye, but am prepared to be- 

 lieve that this is possible by prolonged and careful experiments in which the organisms 

 are exposed to progressively increasing but sub-bactericidal strengths of the dye, 



INFLUENCE OF THE ANILIN DYES UPON PHAGOCYTOSIS AND ANTIBODIES 



Numerous questions naturally arise when the dyes are employed for the treatment 

 of local or general bacterial infections in relation to their influence upon phagocytosis, 

 antibodies, and immunological reactions. For example, may these substances applied 

 locally to infected wounds or serous membranes inhibit phagocytosis of the organisms 

 by leukocytes? May they destroy complement and bacteriolysins by local application 

 or intravenous injection? May they increase antibody production upon intravenous 

 injection or absorption from the subcutaneous tissues, muscles, or gastro-intestinal 

 tract? These questions are not without interest and some practical importance in re- 

 lation to the use of the dyes for therapeutic purposes. 



Naturally most interest has been commanded by the influence of dyes on phago- 

 cytosis since they have been generally employed in the treatment of local infections of 

 wounds and serous cavities, and numerous investigators have shown that it is not 

 advisable to use the dyes in too high concentration for the local treatment of infected 

 wounds, serous cavities, etc. The natural tendency is to employ them in the strong- 

 est solutions free of manifest irritation for the tissues, but this practice may tend to 

 defeat their curative activities by preventing the antibacterial properties of phago- 

 cytosis and bacteriolysis, the influence of which should not be underestimated. 



May the intravenous injection of the dyes increase antibody production? In my 

 experiments I have not found acriflavin, gentian violet, or acid fuchsin, in doses of 

 coio gm, per kilogram by intravenous injection every five days for four to six doses, 

 to influence appreciably either the complement, or the natural or immune antibodies 

 of the blood of rabbits. It may be that a part of the bactericidal effect of gentian 

 violet and acriflavin injected intravenously in the treatment of bacteremias by 

 streptococci and staphylococci is due to increased leukocytosis as well as the mobi- 

 lization of various enzymes, but I doubt that the dyes actually increase antibody or 

 complement production by stimulation of the bone marrow and other tissues be- 

 lieved to be concerned in their production. 



