Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Respirology. 2010 May;15(4):603-22. doi: 10.1111/j.1440-1843.2010.01751.x. Epub 2010 Apr 7.
Isoniazid (INH) has been the mainstay of treatment of latent tuberculosis infection for almost 50 years. The currently recommended preferred regimen is 9 months daily self-administered INH (9H); this has efficacy of more than 90% if completed properly. Unfortunately, INH is associated with serious adverse events, including hepatotoxicity. Although risk factors for this complication are well established, allowing for better selection of candidates for therapy, this complication still occurs, and is occasionally fatal. Hence close follow up of patients is necessary, increasing the cost and complexity of treatment. This problem, plus the lengthy duration, results in poor acceptance by patients and providers, and poor adherence by patients. As a result, many preventable cases of tuberculosis continue to occur, and the public health impact of latent tuberculosis infection treatment is suboptimal. These problems have spurred interest in finding shorter, safer and cheaper alternative regimens, with similar efficacy. Of the many regimens that have been examined, 2 months of rifampin and pyrazinamide has excellent efficacy-in experimental studies in mice and randomized trials, largely in HIV-infected persons. However, while the safety of 2 months of rifampin and pyrazinamide appears acceptable in HIV-infected persons and children, in non-HIV-infected adults this regimen is associated with an unacceptably high rate of severe liver toxicity. Three to four months of INH and rifampin has had equivalent effectiveness as 6 months INH in several randomized trials. However, completion of therapy and toxicity has been the same as with INH-possibly because two drugs are taken rather than one. The fourth commonly studied regimen is 4 months rifampin. This has been found to have significantly better completion than 9H, with significantly less toxicity, especially hepatotoxicity. However, only one trial has evaluated efficacy and effectiveness of mono-rifampin therapy. In this trial, 3 months rifampin had somewhat better efficacy than either 3 months of isoniazid and rifampin (3HR) or 6 months isoniazid. Two large scale trials are ongoing; one is comparing efficacy and effectiveness of 9H with 4 months rifampin (both daily and self-administered), while the second, which is nearing completion, compares daily self-administered 9H with 3 months directly observed once weekly INH combined with rifapentine. The results of these two trials will likely shape future recommendations substantially.
异烟肼(INH)已作为治疗潜伏性结核感染的主要药物近 50 年。目前推荐的首选方案是 9 个月每日自行服用异烟肼(9H);如果正确完成,其疗效超过 90%。不幸的是,异烟肼与严重的不良反应有关,包括肝毒性。尽管该并发症的危险因素已得到充分确立,从而能够更好地选择治疗候选者,但这种并发症仍然会发生,偶尔甚至是致命的。因此,需要对患者进行密切随访,这增加了治疗的成本和复杂性。这个问题,再加上治疗时间长,导致患者和提供者的接受程度差,以及患者的依从性差。因此,许多可预防的结核病病例仍在继续发生,潜伏性结核感染治疗对公共卫生的影响并不理想。这些问题激发了人们寻找更短、更安全、更便宜的替代方案的兴趣,这些方案具有相似的疗效。在已经检查过的许多方案中,2 个月的利福平加吡嗪酰胺在实验性的小鼠研究和随机试验中具有极好的疗效,主要在 HIV 感染者中。然而,虽然 2 个月的利福平加吡嗪酰胺在 HIV 感染者和儿童中的安全性似乎可以接受,但在非 HIV 感染者的成年人中,这种方案与无法接受的高严重肝毒性发生率相关。在几项随机试验中,3 至 4 个月的异烟肼加利福平与 6 个月的异烟肼疗效相当。然而,与异烟肼治疗一样,完成治疗和毒性是一样的,这可能是因为服用了两种药物而不是一种。第四个常用的方案是 4 个月的利福平。这项研究发现,与 9H 相比,它的完成率显著提高,毒性显著降低,特别是肝毒性。然而,只有一项试验评估了单利福平治疗的疗效和有效性。在这项试验中,3 个月的利福平的疗效略优于 3 个月的异烟肼加利福平(3HR)或 6 个月的异烟肼。两项大型试验正在进行中;一项比较 9H 和 4 个月利福平(每日和自我管理)的疗效和有效性,另一项接近完成,比较每日自我管理的 9H 与每周一次直接观察的 3 个月异烟肼联合利福喷丁。这两项试验的结果可能会大大改变未来的推荐。