CHAPTER 6 



ANTIBACTERIAL SUBSTANCES USED IN THE TREATMENT 



OF INFECTIONS 



Since the discovery of the disinfectant action of substances on micro-organisms 

 many attempts have been made to use antimicrobial substances for treating 

 infections of the living animal. Most of these attempts were abortive, for a great 

 number of disinfectants belong to the class of general protoplasmic poisons, and 

 are as likely to kill the host's tissues as they are to kill the parasites infecting 

 the tissues. Only antimicrobial substances with a selective action on the parasite 

 would be suitable ; and the ideal therapeutic agent would be entirely selective, 

 having no action whatsoever on the host's tissues. This ideal has seldom been 

 approached, and we have for the most part to be content with substances that 

 are antimicrobial in concentrations that do not seriously damage the host. There 

 are two types of antibacterial substances to consider, namely, synthetic drugs — 

 the chemotherapeutic agents, etc. — and natural substances, like quinine or penicillin, 

 which are elaborated by plants, moulds and bacteria — the so-called antibiotic 

 agents. 



Chemotherapy was first consistently successful with protozoal and spirochsetal 

 infections, as a result of the great pioneer work of Ehrhch, which started in 1905 

 with a systematic search for a cure for syphilis. The research culminated in the 

 estabhshment of arsphenamine, an organic compound of arsenic, as a cure both 

 for syphilis and for a number of other spirochsetal diseases. The organical arseni- 

 cals, and synthetic dyes like trypan red and trypan blue, were also useful in 

 the treatment of trypanosomiasis. It is beyond the scope of this book to treat 

 of the chemotherapy of these and other protozoal infections ; the student is referred 

 to the standard work of Kolmer (1926) for details. There are, however, a number 

 of noteworthy points to bear in mind in approaching the chemotherapy of bacterial 

 infections. 



Ehrlich devised a measure of chemotherapeutic eflS.ciency, the therapeutic 

 index, which in essence is the ratio of the dose tolerated by the host to the dose 

 that cures the infection. Clearly the measure can give us no more than an indica- 

 tion of the magnitude of the differences in susceptibility to the drug of the host 

 and the parasite. The index would be precise only in an animal whose tissues 

 were uniformly infected by the parasite, receiving a single systemic injection of 

 the drug. Variation in susceptibiUty of different tissues, uneven distribution of 

 parasites in certain organs or in closed lesions of the host, and repeated doses 

 of the drug in sub-toxic concentration, may alter the circumstances so as to make 

 the ratio inapplicable. Nevertheless, for the purposes of investigation, as far as 

 possible using standardized experimental animals with an infection that conforms 



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