Infectious multiple drug resistance / S. Falkow.

  • Falkow, Stanley.
Date:
1975
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Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Infectious multiple drug resistance / S. Falkow. Source: Wellcome Collection.

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    2 Chapter 1 characteristic for penicillin, tetracycline, and chloramphenicol. One would expect therefore that development of resistance to penicillin, for example, might be a prolonged, arduous process. Indeed, whilst the development of penicillin resistance in the pneumococcus and gonococcus can be accomplished in the laboratory by sequential growth in the presence of the drug, nonetheless, after thirty years of penicillin therapy, the pneumococcus has yet to show a significant degree of penicillin resistance and the gonococcus has only just recently begun to show increased resistance to this drug. The correlation between the studies in vitro and the resistance patterns characteristic of naturally occurring strains seemed most satisfactory at first view. 1.1 Mutation is not the only answer Staphylococci, like the pneumococcus and gonococcus, show resistance in vitro to penicillin after sequential growth in the presence of increasing amounts of the drug. The staphylococci, however, unhke the pneumococcus and gonococcus, have been the cause of great clinical concern because of the prevalence of penicilUn-resistant strains. What is different about the staphylococci? The answer is that clinical isolates of staphylococci have acquired a mechanism of penicilhn resistance, the ability to produce penicillinase, which cannot be dupUcated in the laboratory despite numerous attempts by many investigators. Moreover it was observed as early as 1949 by Mary Barber that staphylococci spontaneously lose the ability to produce penicillinase at a relatively high rate and that reverse mutations to penicillinase production did not occur. More will be said about drug resistance in staphylococci in later pages, but for the moment one can simply say that both of these observations suggested that mutation was not a satisfactory explanation of the mechanism of penicillin resistance in staphylococci. In the Enterobacteriaceae also, several observations were recorded which indicated that the origin of drug- resistant strains could be accounted for by a mechanism other than mutation and selection. At the end of World War 2 the sulphonamides (Su) were found to be most effective against the Shigella causing outbreaks of dysentery in Japan. According to surveys, however, this effectiveness lasted for only a relatively few years and by 1952 more than 80% of the Shigella isolates were highly resistant to sulphonamides. The introduction of streptomycin (Sm), tetracycline (Tc), and chloramphenicol (Cm) to Japan in 1950 was subsequently followed by their extensive use and, as might be expected, some resistance to these agents was encountered. Initially, strains were resistant to either tetracycline or streptomycin alone but, in 1956, Kitamoto reported the isolation of a Shigella flexneri 4a strain resistant to streptomycin, tetracycUne, chloramphenicol, and sulphonamides. By 1957, a significant number of Shigella strains showing multiple resistance were