02217nas a2200289   4500000000100000008004100001260001300042653001200055653002600067653001200093653003000105653001100135653001300146653002300159653001200182653000900194653001800203653002500221100001500246700001400261245018600275856004100461300001000502490000700512520139400519022001401913       1982                            d  c1982 Mar10aAnimals10aAntitubercular Agents10aDapsone10aDrug Therapy, Combination10aHumans10aKinetics10aLeprostatic Agents10aleprosy10aMice10aMycobacterium10aMycobacterium leprae1 aSeydel J K1 aWempe E G00aBacterial 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 M. leprae?  uhttp://ila.ilsl.br/pdfs/v50n1a03.pdf  a20-300 v503 a<p>Bacterial growth kinetic studies were performed in a series of potential inhibitors of M. leprae using "M. lufu" as a model strain. Reasons why "M. lufu" is considered to be a better model than M. tuberculosis are presented. The inhibitory 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. It is demonstrated that a combination consisting of dapsone (DDS), prothionamide (PTH), isoniazid (INH), and rifampin (RAMP) 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 eradication program on the Island of Malta. Whereas there is no 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."</p>
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