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鸟分枝杆菌胞内复合群肺病治疗中微生物学结局的Meta分析及证据基础

Meta-analyses and the evidence base for microbial outcomes in the treatment of pulmonary Mycobacterium avium-intracellulare complex disease.

作者信息

Pasipanodya Jotam G, Ogbonna Deborah, Deshpande Devyani, Srivastava Shashikant, Gumbo Tawanda

机构信息

Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA.

出版信息

J Antimicrob Chemother. 2017 Sep 1;72(suppl_2):i3-i19. doi: 10.1093/jac/dkx311.

Abstract

OBJECTIVES

To perform a systematic review and meta-analysis of the level of funding support and the sputum culture conversion rates in pulmonary Mycobacterium avium-intracellulare complex (P-MAC) disease in adult patients without cystic fibrosis or HIV infection, treated with recommended antibiotic regimens.

METHODS

We performed a literature search to identify clinical trials, prospective studies and registries that reported outcomes in P-MAC patients. Studies that reported P-MAC diagnosis and treatments based on established guidelines met the inclusion criteria and were examined for bias and quality. We modified existing quality scales and came up with a 10 star quality score. Outcomes meta-analysed were sputum conversion incidence ratios (IR) and their 95% CI, weighted for study quality.

RESULTS

Twenty-one studies that examined 28 regimens, including 2534 patients in intent-to-treat analyses and 1968 in per-protocol analyses, were identified. The study quality mean ± SD scores were 5.4 ± 2.2 out of 10 stars. Only two (9.5%) studies received public funding. There was significant heterogeneity of microbial effect among treatment regimens (I2 > 40%; P > 0.001). The pooled IR for sustained sputum conversion was 0.54 (95% CI 0.45-0.63) for macrolide-containing regimens versus 0.38 (0.25-0.52) with macrolide-free regimens. Prolonging therapy duration beyond 12 months was associated with an average decline in sputum conversion to 22% (95% CI 1%-44%).

CONCLUSIONS

Researchers working on P-MAC therapy have received very little public funding support. As a result, the evidence base for treatment guidelines is based on studies of relatively small numbers of patients in low-quality studies. Nevertheless, these studies showed poor sputum conversion rates in patients receiving recommended treatment regimens.

摘要

目的

对在无囊性纤维化或HIV感染的成年患者中,采用推荐抗生素方案治疗的肺部鸟分枝杆菌复合群(P-MAC)疾病的资金支持水平和痰培养转化率进行系统评价和荟萃分析。

方法

我们进行了文献检索,以确定报告P-MAC患者结局的临床试验、前瞻性研究和登记处。根据既定指南报告P-MAC诊断和治疗的研究符合纳入标准,并对其偏倚和质量进行检查。我们修改了现有的质量量表,并得出了一个10星质量评分。荟萃分析的结局指标是痰转化发病率比(IR)及其95%置信区间,并根据研究质量进行加权。

结果

共纳入21项研究,这些研究检验了28种治疗方案,意向性分析中有2534例患者,符合方案分析中有1968例患者。研究质量的平均±标准差评分为5.4±2.2(满分10星)。只有两项(9.5%)研究获得了公共资金。治疗方案之间的微生物效应存在显著异质性(I2>40%;P>0.001)。含大环内酯类方案的持续痰转化合并IR为0.54(95%CI 0.45-0.63),而不含大环内酯类方案为0.38(0.25-0.52)。将治疗时间延长至12个月以上与痰转化率平均下降至22%(95%CI 1%-44%)相关。

结论

从事P-MAC治疗研究的人员获得的公共资金支持非常少。因此,治疗指南的证据基础是基于低质量研究中相对少量患者的研究。尽管如此,这些研究显示接受推荐治疗方案的患者痰转化率较低。

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