Higher-dose rifampin for the treatment of pulmonary tuberculosis: a systematic review.
Higher-dose rifampin for the treatment of pulmonary tuberculosis: a systematic review.
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发表时间：
2011-03
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通讯作者：
K. Steingart;S. Jotblad;K. Robsky;D. Deck;P. C. Hopewell;D. Huang;P. Nahid
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作者：
K. Steingart;S. Jotblad;K. Robsky;D. Deck;P. C. Hopewell;D. Huang;P. Nahid
目的对评价大剂量利福平(RMP)治疗肺结核疗效和安全性的证据进行描述性综述。方法对评估一系列RMP剂量的随机对照试验进行系统评价，包括高于标准剂量(>；10 mg/kg或>；600 mg)的剂量，作为肺结核联合药物疗法的一部分。两名评价者应用纳入标准，评估试验质量并提取数据。纳入标准为涂片或培养确认的肺结核，以及英语和法语文章。排除标准为RMP单一治疗和涂片阴性结核病。结果包括痰培养转换、治疗失败、复发和不良事件，包括肝毒性和流感样综合征。结果在已确定的14项试验(4256名参与者)中，有12项是在1980年之前进行的。根据公布的指南，四项试验被认为是高质量的。研究的特点多种多样，包括以前的结核病治疗史、RMP剂量、治疗持续时间、引入介入治疗的时间、伴随药物和随访时间，这使得疗效数据的综合具有挑战性。几项试验表明，在接受至少900毫克RMP的患者中，培养转换的可能性方面具有优势。然而，间歇性服用900毫克或更高剂量的RMP会增加流感样综合征的发生率。结论历史试验表明，高于标准的RMP剂量可提高培养转化率。需要评估更高剂量的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。药代动力学研究将需要为此类试验的发展提供信息。
OBJECTIVE 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). METHODS 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. RESULTS 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. CONCLUSION 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.