BACTERIAL-GROWTH KINETICS OF M-LUFU IN THE PRESENCE AND ABSENCE OF VARIOUS DRUGS ALONE AND IN COMBINATION - A MODEL FOR THE DEVELOPMENT OF COMBINED CHEMOTHERAPY AGAINST MYCOBACTERIUM-LEPRAE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 50  (1) , 20-30
Abstract
Bacterial growth kinetic studies were performed in a series of potential inhibitors of M. leprae using [the incompletely classified] M. lufu as a model strain. Reasons why M. lufu is considered to be a better model than M. tuberculosis are presented. The inhibitor power of the single drugs has been quantified, the activity constants are calculated and the synergistic, additive or antagonistic behavior of the combinations is evaluated. A combination consisting of dapsone (DDS), prothionamide (PTH), isoniazid (INH) and rifampin (RAMP) evidently is a very powerful inhibitor of M. lufu and prevents or delays the development of resistance under the experimental conditions described. This finding is in agreement with the therapeutic effect of this combination (Isoprodian + rifampin) achieved in a leprosy (in humans) eradication program on the Island of Malta. Whereas there is not direct proof that M. lufu is the best suitable model for drug evaluation against M. leprae, there is, however, nothing in the presented results which is against this model, especially as the actions of DDS and PTH or RAMP is concerned. A new combination of DDS with trimethoprim (TMP) or TMP derivatives has also been studied and seems to be a promising candidate. In addition, a technique is described to differentiate between bacteriostatic and bactericidal action of the tested inhibitors against M. lufu.