DISTRIBUTION OF DRUG-RESISTANT 



INDIVIDUALS IN CULTURES OF 



MYCOBACTERIUM TUBERCULOSIS 



R. Knox 



Department of Bacteriology, Guy''s Hospital Medical School, London 



Tuberculosis shows perhaps more clearly than any- 

 other disease the dangers associated with the development 

 of drug resistance. With streptomycin, ^-aminosalicylic acid 

 (PAS), isoniazid and other less commonly used drugs, initial 

 success in chemotherapy has often been followed by subse- 

 quent failure associated with the development of drug- 

 resistant strains. In vitro tests of drug sensitivity however 

 are in many respects unsatisfactory, and the information they 

 give is often difficult to interpret and to correlate with results 

 obtained in vivo. One of the reasons for this is the difficulty 

 in obtaining accurate information about the number of viable 

 tubercle bacilli and the proportions of drug-resistant indivi- 

 duals present in a given bacterial population. 



Recently, we have been using semi-solid (0-125 per cent) 

 agar as a convenient medium for rapid culture of Mycobac- 

 terium tuberculosis and for the performance of viable counts 

 (Knox, 1955; Knox, Swait and Woodroffe, 1956). We have 

 also found media of this kind very useful for the performance 

 of drug sensitivity tests and for determining what proportion 

 of individuals in a given culture is resistant to different drug 

 levels (Knox and Woodroffe, 1957). Preliminary work 

 showed some interesting differences between streptomycin, 

 PAS and isoniazid in the patterns of resistance they showed 

 in this medium. It seemed, therefore, that it would be interest- 

 ing to investigate by the use of semi-solid medium the distri- 

 bution of drug-resistant individuals in different conditions of 

 incubation, with different drugs separately and together. 



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