L'approche experimentale de la chimiotherapie de la tuberculose

Because it is easy to handle in terms of size, supply, maintenance, robustness and reproducibility, the mouse infected with Mycobacterium tuberculosis and treated with antimicrobial drugs is the choice model for experimental chemotherapy on tuberculosis. It provides results that may be applied to man on the condition that age, race, body weight of mice are precisely defined as well as the strain of M. tuberculosis used (at best the H37Rv reference strain), the way its virulence is maintained and subcultures are made. In addition, because of the important pharmacokinetic differences between mice and man, antimicrobial drugs should be given to the mouse only at dosages equivalent to those given to man, at best in terms of AUC. Experimental methods to test the activity of a single drug are different from the methods used to test the activity of a drug combination. In the first case to prevent a possible interference with the selection of drug resistant mutants, either mice are infected with 5 x 10³ cfu and the treatment starts two weeks later when the microbial population reaches 10⁶ cfu or they infected with 10⁶ cfu and the treatment starts on the day after infection. In the second case, mice are infected with 5 x 10⁶ cfu and the treatment starts two weeks later when the microbial population reaches 10⁸ cfu. Experimental chemotherapy for tuberculosis could lead to: possible improvements of the present short-course chemotherapy by further shortening the total duration of treatment or by increasing the intervals between drug administration; new regimens for the treatment of multidrug resistant tuberculosis; and curative and preventive treatment of tuberculosis in HIV-infected patients.