[Resistance to antituberculous drugs].
Mycobacteria responsible for tuberculosis (M. tuberculosis, M. bovis, M. africanum) are susceptible to a very small number of antibiotics. As soon as these drugs were used in humans all gave rise to the selection of resistant mycobacteria. Study of the mechanisms of acquired resistance, with the help of the genetics of mycobacteria, led to a more accurate understanding of the mode of action of antituberculous drugs. The antibiotics isoniazid, pyrazinamide, ethionamide and ethambutol are mycobacteria-specific because they inhibit the synthesis of mycolic acids, which are specific constituants of the bacterial wall. Mutations responsible for resistance to these drugs affect genes coding for activator enzymes (katg for isoniazid, pncA for pyrazinamide) or genes coding for their target (inhA for isoniazid/ethionamide, embB for ethambutol). With rifamycins, aminosides and quinolones, mechanisms of action and resistance are the same for mycobacteria as for non-mycobacterial organisms. No plasmid or resistance transposon has been described in M. tuberculosis. Currently a test for the quick detection of resistance to rifampicin is widely available but in the future DNA chips may allow the simultaneous detection of multiple resistances. Monitoring of antituberculous drugs shows that in France the prevalence of multiresistance ( resistance to both isoniazid and rifampicin) is 0.5%, primary resistance (before treatment) is 9%, and secondary resistance (after treatment) is 16%.
Veziris
N
N
Laboratoire de bactériologie-Hygiène, CHU Pitié-Salpêtrière, Assistance-publique-Hôpitaux-de-Paris, 75651 Paris cedex 13, France. veziris@chups.jussieu.fr
Cambau
E
E
Sougakoff
W
W
Robert
J
J
Jarlier
V
V
D000995:Antitubercular Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D012293:Rifampin / Q000494:pharmacology; D018088:Tuberculosis, Multidrug-Resistant
D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin