JOHN A. KOLMER 1109 



may become reinfected a few hours later by organisms from localized lesions escaping 

 disinfection. 



But organisms in the fixed tissues can be reached and destroyed only when suffi- 

 cient amounts of the compound in an active bactericidal state leave the blood and 

 permeate the lesion. This in turn involves the questions of rapidity of elimination, 

 production of inert combination compounds, the physical laws of diffusion, capillary 

 permeability, etc.; it also involves the degree and kind of pathological tissue changes 

 which may be present and which constitute the theme of the present discussion. 



In acute bacterial infections the hyperemia is undoubtedly a favoring factor for 

 bringing the bactericide to the sites of infection, and during the processes of acute 

 cellular and serous exudation a part of it may be swept along into the inflammatory 

 exudates even though the compound itself does not possess the physical character- 

 istics which facilitate its passage through the walls of normal vessels. Permeability is 

 of fundamental importance, but in acute inflammatory lesions it may not be as im- 

 portant as in chronic lesions because of the opportunities, in the former, for the com- 

 pound's being carried along mechanically into the infected tissues by the processes just 

 mentioned. We may expect, therefore, better results in acute than in chronic infec- 

 tions. But even when compounds like mercurochrome, acriflavin, gentian violet, 

 optochin, etc., leave the capillaries their diffusion may be hindered by the physical 

 characteristics of the edematous fluid and pus as well as by the leukocytes and other 

 cells containing many of the organisms. The problems, therefore, are many and diffi- 

 cult, and particularly good results may not be obtained until we learn more about the 

 laws governing permeability and diffusion under these circumstances and until we 

 succeed in evolving compounds which will accumulate in the lesions to reach bac- 

 tericidal concentrations. This, I believe, occurs with mercury in the treatment of 

 syphilis and explains its peculiar efficacy in this disease. 



In chronic bacterial diseases the lesions may be quite avascular as in the case of 

 tuberculosis; furthermore, many of the blood vessels are likely to be sclerosed, which 

 may amount to occlusion of the smaller vessels. Serous and cellular exudation are re- 

 duced to a minimum, and we have therefore a set of circumstances very unfavorable 

 for chemotherapy, especially if our compounds possess but feeble permeability for 

 capillaries at best and a low diflfusibility in the products of caseation and liquefying 

 necrosis. 



Needless to state, the pathological lesions produced by bacterial infections may 

 also influence the organotropism or toxicity of compounds for the body cells. It is 

 commonly observed that the tolerance of infected animals for a drug is appreciably 

 less than in normal animals, and I believe the same is true of human beings. The 

 bacterial toxins and exudates are always likely to produce albuminous degeneration 

 of the kidneys, heart, and other organs which may proceed to more advanced lesions 

 and interfere with elimination to such an extent as may increase the chances for 

 toxic effects and especially in the case of chronic diseases. On the other hand, just 

 the opposite may occur during the acute stages; for example, the patient with croup- 

 ous pneumonia has, I believe, a higher tolerance for optochin and quinin compounds 

 in general than normal human beings. This is analogous to the increased tolerance 

 of syphilitics for mercury and of malarial-infected individuals for quinin. In other 



