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• W2068045331 abstract "30 years ago, Canetti warned implicitly ‘. . . Since optimal chemotherapy of tuberculosis produced by wild strains reduces the frequency of emergence of resistance drastically, the general feeling tends to prevail that resistance has slipped into history . . .‘I The medical community has subsequently learned the hard way, from experience in the USAzA and elsewhere,5” that Canetti really meant optimal chemotherapy and not availability of optimal drugs. The British Medical Research Council’s streptomycin trial7 revealed early on what is now abundantly clear: in each wild strain of tubercle bacilli, approximately 1 out of every l-10 000 000 organisms is spontaneously resistant to at least 1 of the known drugs.* Because patients with cavitary pulmonary lesions may harbor 10 000 000-l 000 000 000 tubercle bacilli,’ any patient treated with only a single effective drug has a very high probability that the drug-resistant mutants are preferentially selected while the susceptible ones are killed off. Conversely, a patient continuously treated with 2 or more drugs, in concentrations to which the strain is susceptible, has a very high probability of escaping the fate of incurable drug-resistant tuberculosis. The role of chemotherapy is paramount in the production of all clinically important drug resistance. Three phases in the development of antituberculosis chemotherapy might be distinguished. They are characterized by increasing knowledge about principles of treatment, accompanied by neglect of that knowledge by large segments of the medical community. The first phase began with the discovery of streptomycin and the early observation of the iatrogenic creation of streptomycin resistance in clinical trials. An insight into the harm inflicted by monotherapy was gained in this period. In the second phase, it was shown that streptomycin resistance could be largely overcome with the addition of para-aminosalicylic acid and isoniazid, and" @default.
• W2068045331 created "2016-06-24" @default.
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• W2068045331 date "1994-10-01" @default.
• W2068045331 modified "2023-09-29" @default.
• W2068045331 title "Drug-resistant tuberculosis: issues in epidemiology and challenges for public health" @default.
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• W2068045331 doi "https://doi.org/10.1016/0962-8479(94)90075-2" @default.
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