The Correlation between the Inhibition of Drug Resistance and Synergism in Streptomycin and Penicillin.

The problem of drug resistance has become an important limiting factor in the therapeutic efficiency of streptomycin (Buggs et al., 1946; Finland et al., 1946; Bondi et al., 1946). We have previously shown in the case of streptomycin that of 13 strains tested all had the ability to throw off, spontaneously, variants resistant to streptomycin (Klein and Kimmelman, 1946; Klein, 1947). The destruction by streptomycin of the mass of susceptible bacteria and the multiplication of the fe.w highly resistant variants was indicated to be a mechanism for the development of streptomycin resistance. Alexander and Leidy (1947), working with Hemophilus influertae, have recently obtained similar results. Clinically, the inhibition of the rapid development of streptomycin resistance may then require the destruction of a relatively small number of resistant bacteria, which might be effected by the addition of a low concentration of another drug. In the present work we have therefore studied the combined action of streptomycin, penicillin, and sulfadiazine in vitro and determined the relationship between the synergistic action of the compounds and the inhibition of the development of streptomycin resistance.