Curry International Tuberculosis Center, University of California, San Francisco, California, USA.
Int J Tuberc Lung Dis. 2011 Mar;15(3):305-16.
To provide a descriptive synthesis of the evidence assessing the efficacy and safety of higher doses of rifampin (RMP) for the treatment of pulmonary tuberculosis (TB).
Systematic review of randomized controlled trials that evaluate a range of RMP doses, including doses higher than standard (>10 mg/kg or >600 mg), used as part of combination drug therapies for pulmonary TB. Two reviewers applied inclusion criteria, assessed trial quality and extracted data. Inclusion criteria were smear- or culture-confirmed pulmonary TB, and English and French language articles. Exclusion criteria were RMP monotherapy and smear-negative TB. Outcomes included were sputum culture conversion, treatment failure, recurrence and adverse events, including hepatotoxicity and flu-like syndrome.
Of 14 trials (4256 participants) identified, 12 were conducted before 1980. Four trials were considered high quality according to published guidelines. Study characteristics, including history of prior TB treatment, dose of RMP, duration of treatment, timing of introduction of intervention treatment, concomitant drugs, and duration of follow-up, varied, making synthesis of efficacy data challenging. Several trials suggested an advantage in terms of likelihood of culture conversion among patients receiving at least 900 mg RMP. However, an increased incidence of flu-like syndrome was seen when RMP doses of 900 mg and higher were given intermittently.
Historical trials suggest that higher than standard RMP dosing results in improved culture conversion rates. Phase 2 and 3 clinical trials evaluating higher doses of RMP and other rifamycins are needed to confirm efficacy and assure tolerability. Pharmacokinetic studies will be needed to inform the development of such trials.
对评估利福平（RMP）高剂量治疗肺结核（TB）疗效和安全性的证据进行描述性综合分析。
系统评价评估各种 RMP 剂量的随机对照试验，包括高于标准（>10mg/kg 或>600mg）的剂量，作为肺结核联合药物治疗的一部分。两名审查员应用纳入标准，评估试验质量并提取数据。纳入标准为涂片或培养证实的肺结核，以及英语和法语文章。排除标准为 RMP 单药治疗和涂片阴性的 TB。结局包括痰培养转换、治疗失败、复发和不良反应，包括肝毒性和流感样综合征。
共确定了 14 项试验（4256 名参与者），其中 12 项试验在 1980 年之前进行。根据已发表的指南，有 4 项试验被认为是高质量的。研究特征，包括既往 TB 治疗史、RMP 剂量、治疗持续时间、干预治疗的引入时间、伴随药物以及随访时间的长短各不相同，使得疗效数据的综合分析具有挑战性。几项试验表明，接受至少 900mg RMP 治疗的患者在培养转换的可能性方面有优势。然而，当给予 900mg 及更高剂量的 RMP 间歇给药时，会出现更高的流感样综合征发生率。
历史试验表明，高于标准的 RMP 剂量可提高培养转换率。需要进行评估更高剂量的 RMP 和其他利福霉素的 2 期和 3 期临床试验，以确认疗效并确保耐受性。需要进行药代动力学研究，为这些试验的开展提供信息。
