Role of individual drugs in the chemotherapy of tuberculosis.
During the course of chemotherapy, certain drugs are predominant in their bactericidal activities. Isoniazid is responsible for an initial kill of about 95% of organisms during the first 2 days of treatment. Its bactericidal role is then replaced by rifampicin and pyrazinamide during the intensive phase. In the continuation phase with an isoniazid/rifampicin regimen, rifampicin is the only effective drug against persisters, as shown by the similarity of response by patients with initially isoniazid-resistant or sensitive strains. If the continuation phase regimen does not contain rifampicin but does contain isoniazid, the dominant bactericidal drug is isoniazid. In this case, the response of patients with initial isoniazid resistance is appreciably less good than in those with sensitive organisms. The review suggests exploration in randomised control trials of a continuation phase of rifampicin (or rifapentine) alone. It also suggests the importance of the dose size of rifampicin and the need for exploring a higher dose. Finally, it emphasises the importance of finding drugs that act on persisting organisms that are phenotypically but not genetically resistant to rifampicin.
Mitchison
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DA
Department of Medical Microbiology, St George's Hospital Medical School, London, UK. dmitchis@sghms.ac.uk
D000904:Antibiotics, Antitubercular / Q000494:pharmacology / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D011322:Primary Prevention / Q000379:methods; D011718:Pyrazinamide / Q000494:pharmacology / Q000627:therapeutic use; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin