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Category: Bacterial Pathogenesis
Antibacterial Treatment of Leprosy, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555815929/9781555812379_Chap46-1.gif /docserver/preview/fulltext/10.1128/9781555815929/9781555812379_Chap46-2.gifAbstract:
Acquired resistance of Mycobacterium lepraeto the thioamides has been demonstrated in patients suffering from lepromatous leprosy treated with thioamides alone. Only the antibacterial treatment of leprosy, the principles on which it is based, the combinations with recommended antibiotics, and the results obtained to date in the field are discussed in this chapter. The whole argument behind modern chemotherapy of leprosy is based on the treatment of lepromatous or multibacillary leprosy, in the same way that the rationale for the chemotherapy of tuberculosis is based on the treatment of patients suffering from cavitary pulmonary tuberculosis. Dapsone, rifampin, and clofazimine therefore are automatically part of the initial phase of the chemotherapy of leprosy. From 109 at the beginning of treatment, the total number of viable M. leprae bacilli in a patient suffering from multibacillary leprosy therefore fell to 104! The majority of susceptible bacilli and mutants resistant to dapsone and clofazimine, which by definition are susceptible to rifampin, were eliminated. The first reason for continuing treatment beyond the first doses of rifampin is to prevent the risk of selection of rifampin-resistant bacilli. The second reason is that after very short-term multidrug therapy in patients suffering from Bamako multibacillary leprosy, it was found that the shorter the duration of antibiotic administration, the earlier relapses occurred. It is difficult to reduce the duration of the multidrug therapy recommended by the WHO. It is based on the combination of the three best-tolerated antibiotics, rifampin, dapsone, and clofazimine, of which only rifampin is highly bactericidal.
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Comparative chemical structures of sulfanilamide, dapsone, and acedapsone
Rifampin
Structure of the clofazimine molecule
Chemical structure of ethionamide and protionamide
Principal viable microbial populations in multibacillary leprosy and their response to multidrug therapy during initial phase of treatment
Regression of the total number of M. leprae bacilli and the probable number of viable M. leprae bacilli persisting on multidrug therapy in multibacillary leprosy
Principal pharmacokinetic parameters of the four antileprosy antibiotics
Susceptibilities to dapsone and rifampin of strains of M. leprae isolated from previously treated patients (acquired resistance)
Susceptibilities to dapsone and rifampin of strains of M. leprae isolated from previously untreated patients (primary resistance)
Relationship between the duration of treatment with rifampin and early and late relapse rates a
Relationship between bacteriological index on discontinuation of treatment and relapse rate a