Mitchison D A
Department of Medical Microbiology, St George's Hospital Medical School, London, UK.
Int J Tuberc Lung Dis. 2000 Sep;4(9):796-806.
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.
在化疗过程中，某些药物在杀菌活性方面占主导地位。异烟肼在治疗的头两天负责杀灭约95%的病原体。在强化期，其杀菌作用随后被利福平和吡嗪酰胺取代。在异烟肼/利福平方案的持续期，利福平是唯一对持续菌有效的药物，这一点从初始异烟肼耐药或敏感菌株患者的反应相似性可以看出。如果持续期方案不含利福平但含异烟肼，主要的杀菌药物就是异烟肼。在这种情况下，初始异烟肼耐药患者的反应明显不如敏感菌患者。该综述建议在随机对照试验中探索单独使用利福平（或利福喷汀）的持续期。它还表明了利福平剂量大小的重要性以及探索更高剂量的必要性。最后，它强调了找到作用于对利福平表型耐药但非基因耐药的持续菌的药物的重要性。
