1 1 12 CHEMOTHERAPY OF BACTERIAL DISEASES 



Practically only the synthetic dyestuffs prepared from coal tar have been em- 

 ployed for the staining of bacteria and for bacteriostatic and bactericidal purposes. 

 Natural dyes, like Indian yellow, quercetin, chrysin, cochineal, carmine, cudbear, 

 hydrastis, etc., have been proved to be without parasiticidal properties and have not 

 been employed for these purposes. 



A very large number of dyes have been prepared from coal tar, and their chemis- 

 try is exceedingly involved, the exact constitution of not a few being still in dispute 

 and their preparation kept as trade secrets. Furthermore, the various dyes as avail- 

 able are not always in a pure state and sometimes vary greatly in their staining prop- 

 erties, toxicity, bacteriostatic and bactericidal activity. Those mostly employed have 

 belonged to the nitroso, azo, triphenylmethane, diphenylamin, acridin, and pyronin 

 groups. 



BACTERIOSTATIC AND BACTERICmAL ACTIVITY OF THE SYNTHETIC 

 DYES IN RELATION TO CHEMOTHERAPY 



The synthetic dyes vary greatly in bacteriostatic and bactericidal activity. Some 

 dyes, and especially certain members of the triphenylmethane and acridin series, like 

 gentian violet, acid and basic fuchsin, brilliant green, acrifiavin, proflavin and 

 rivanol, are very highly bactericidal, while others like methylene blue and fluorescein 

 are relatively feeble and mainly employed in chemotherapy for the purpose of com- 

 bination with mercury or some other more highly bactericidal substances for aiding 

 penetrability. Gentian violet and magenta may inhibit the growth of staphylococci 

 and streptococci in culture media in dilutions as high as 1:100,000 to 1:1,000,000 

 in agar or egg medium and are commonly employed for aiding in the isolation of tu- 

 bercle bacilli and organisms of the typhoid-colon group. 



As a general rule, however, the majority of anilin dyes are relatively feeble in 

 bactericidal activity, and especially in the presence of serum, blood, pus, and other 

 organic matters. Probably gentian violet, acid fuchsin, brilliant green, and acrifiavin 

 possess the highest bacteriostatic and bactericidal properties, gentian violet being par- 

 ticularly destructive for gram positive bacteria and the fuchsins for gram negative 

 bacilli; but even dyes of the same series vary greatly in these properties. 



Of great interest and importance in relation to the chemotherapy of bacteremia 

 is the question of bactericidal activity and fate of the dyes when introduced into the 

 blood, usually by intravenous injection. This has been studied by injecting the dyes 

 and withdrawing blood at intervals for bactericidal tests and also by producing ex- 

 perimental bacteremias of rabbits and treating with intravenous injections of the 

 dyes. From such experiments it would appear that large doses of gentian violet and 

 acrifiavin injected intravenously may at least temporarily increase the bactericidal 

 activity of the blood (for about an hour), but these effects may not be sufficient for 

 materially infiuencing a severe experimentally produced bacteremia, since the dyes 

 are rapidly absorbed by the tissues. 



BACTERICroAL ACTIVITY OF MIXTURES OF THE DYES 



The question of the bactericidal activity of mixtures of various dyes deserves 

 brief consideration. Gay and Morrison have tested various combinations for strepto- 

 cocci, staphylococci, and typhoid bacilli and found that the final bactericidal dilution 



