Centre for the AIDS Programme of Research in South Africa, Nelson R Mandela School of Medicine, College of Health Sciences, Medical Research Council-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, Department of Pulmonology and Critical Care, Groote Schuur Hospital, University of Cape Town, South Africa.
Centre for the AIDS Programme of Research in South Africa, Nelson R Mandela School of Medicine, College of Health Sciences, Department of Pulmonology and Critical Care, Groote Schuur Hospital, University of Cape Town, South Africa.
Int J Tuberc Lung Dis. 2020 Jan 1;24(1):48-64. doi: 10.5588/ijtld.19.0025.
Low serum concentrations of first-line tuberculosis (TB) drugs have been widely reported. However, the impact of low serum concentrations on treatment outcome is less well studied. A systematic search of MEDLINE/Pubmed and the Cochrane Central Register of Controlled Trials up to 31 March 2018 was conducted for articles describing drug concentrations of first-line TB drugs and treatment outcome in adult patients with drug-susceptible TB. The search identified 3073 unique publication abstracts, which were reviewed for suitability: 21 articles were acceptable for inclusion in the qualitative analysis comprising 13 prospective observational cohorts, 4 retrospective observational cohorts, 1 case-control study and 3 randomised controlled trials. Data for meta-analysis were available for 15 studies, 13 studies of rifampicin (RMP), 10 of isoniazid (INH), 8 of pyrazinamide (PZA) and 4 of ethambutol (EMB). This meta-analysis revealed that low PZA concentration appears to increase the risk of poor outcomes (8 studies, = 2727; RR 1.73, 95%CI 1.10-2.72), low RMP concentrations may slightly increase the risk of poor outcomes (13 studies, = 2753; RR 1.40, 95%CI 0.91-2.16), whereas low concentrations of INH (10 studies, = 2640; RR 1.32, 95%CI 0.66-2.63) and EMB (4 studies, = 551; RR 1.12, 95%CI 0.41-3.05) appear to make no difference to treatment outcome. There was no significant publication bias or between-study heterogeneity in any of the analyses. The potential clinical impact of low concentrations of PZA and RMP warrants further evaluation. Also, comprehensive assessments of the complex pharmacokinetic-pharmacodynamic relationships in the treatment of TB are urgently needed.
血清中一线抗结核药物浓度降低的情况已被广泛报道。然而，药物浓度降低对治疗结果的影响研究较少。本研究系统检索了 MEDLINE/Pubmed 和 Cochrane 中央对照试验注册库，检索时间截至 2018 年 3 月 31 日，以获取描述成人耐多药结核病患者一线抗结核药物药物浓度和治疗结果的文章。共检索到 3073 个独特的文献摘要，对其进行了适宜性评估：21 篇文章纳入定性分析，包括 13 项前瞻性观察队列研究、4 项回顾性观察队列研究、1 项病例对照研究和 3 项随机对照试验。meta 分析获得了 15 项研究的数据，其中 13 项为利福平（RMP）、10 项为异烟肼（INH）、8 项为吡嗪酰胺（PZA）和 4 项为乙胺丁醇（EMB）。meta 分析显示，低 PZA 浓度似乎增加不良结局风险（8 项研究， = 2727；RR 1.73，95%CI 1.10-2.72），低 RMP 浓度可能轻微增加不良结局风险（13 项研究， = 2753；RR 1.40，95%CI 0.91-2.16），而低 INH 浓度（10 项研究， = 2640；RR 1.32，95%CI 0.66-2.63）和 EMB 浓度（4 项研究， = 551；RR 1.12，95%CI 0.41-3.05）似乎对治疗结果无影响。任何分析均未发现明显的发表偏倚或研究间异质性。需要进一步评估 PZA 和 RMP 浓度降低的潜在临床影响。此外，迫切需要全面评估结核病治疗中复杂的药代动力学-药效学关系。
