150 



OXIDATION-REDUCTION POTENTIALS 



One disadvantage of streptomycin in treatment is the ease with which strains of 

 bacteria become resistant to it. This is particularly disadvantageous in long-contin- 

 ued treatment of tuberculosis. Some observations in the case of C. dipJithericB may 

 be mentioned (Hewitt, 1948, a). Active prophylaxis is reducing the incidence of 

 diphtheria, but carriers remain and hospital treatment is frequently unduly prolonged 

 owing to the persistence of the organisms in the throat, so an effective bactericidal 

 agent was sought. Although inferior to penicillin in its in vitro bacteriostatic activity 

 against C. dipJdhericB streptomycin proved very much superior in saving guinea-pigs 

 infected with the organisms. Resistant strains were, however, developed rapidly 

 in vitro in the case of some strains and these strains were also resistant to strepto- 

 mycin in vivo, so that adequate initial dosage is necessary to minimise the risk of 

 development of resistance. The development of streptomycin resistance did not 

 affect toxin production or the pathogenicity of the organisms. 



In view of the two basic guanido groups in streptomycin it was thought possible 

 that the two basic groups in the diamidines might point to a similar mechanism of 

 effect. Hence strains of C. diphthericB were made resistant to various diamidines, to 

 streptomycin and to both (Hewitt, 1948, b). 



TABLE 29 

 Bacterial Resistance to Streptomycin and Diamidines 



TABLE 30 

 Cross-resistance of C. Diphtheriae to Diamidines 



It will be seen that there is no cross-resistance developed between the strepto- 

 mycin-resistant organisms and the diamidine-resistant strains, although organisms 

 which developed resistance to one of the diamidines were resistant to the others. 

 Hence it would appear that the mechanism of the effect of streptomycin is different 

 from that of the diamidines despite their common basic groups. 



