Metrics for Public Health Perspective Surveillance of Bacterial Antibiotic Resistance in Low- and Middle-Income Countries

Metrics for Public Health Perspective Surveillance of Bacterial Antibiotic Resistance in Low- and Middle-Income Countries
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低收入和中等收入国家细菌抗生素耐药性的公共卫生视角监测指标

DOI:
10.1101/2020.02.10.941930
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发表时间:
2020
期刊:
--
影响因子:
--
通讯作者:
Auguet O
Auguet O
中科院分区:
--
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作者:
Auguet O

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抗生素耐药性 (AMR) 是一种全球性健康威胁,特别是在低/中等收入国家 (LMIC),这些国家的监测能力有限,无法为经验性抗生素治疗指南提供信息。肠杆菌目是耐药细菌感染的最重要原因之一。我们开发了一种新型的肠杆菌 AMR 监测方法,通过对来自三个地点(n=563 人;柬埔寨、肯尼亚、英国)的人类粪便宏基因组进行分析,得出分类调整后的 AMR 指标(“耐药潜力”),该指标可用于预测每个环境中耐药侵袭性肠杆菌感染的总百分比。对样品进行测序(Illumina);使用 ResPipe 进行分类学和抗性基因分析。对每个地点 2010 年至 2017 年引起菌血症和脑膜炎的微生物数据以及抗生素敏感性测试结果进行了整理。拟合具有二项式似然的贝叶斯广义线性模型,以确定预测每种环境中肠杆菌感染 AMR 的耐药潜力的能力。信息最丰富的模型准确预测了英国 14/14 的抗生素目标人群、肯尼亚的 12/12 和柬埔寨的 9/12 的目标人群中耐药感染的数量。混合人类样本的间歇性宏基因组学可以代表一种强大的实用且经济的方法,用于确定和监测临床感染中的 AMR,特别是在资源有限的环境中。
Antimicrobial resistance (AMR) is a global health threat, especially in low-/middle-income countries (LMICs), where there is limited surveillance to inform empiric antibiotic treatment guidelines. Enterobacterales are amongst the most important causes of drug-resistant bacterial infections. We developed a novel AMR surveillance approach for Enterobacterales by profiling pooled human faecal metagenomes from three sites (n=563 individuals; Cambodia, Kenya, UK) to derive a taxonomy-adjusted AMR metric (“resistance potential”) which could be used to predict the aggregate percentage of resistant invasive Enterobacterales infections within each setting. Samples were sequenced (Illumina); taxonomic and resistance gene profiling was performed using ResPipe. Data on organisms causing bacteraemia and meningitis and antibiotic susceptibility test results from 2010-2017 were collated for each site. Bayesian generalised linear models with a binomial likelihood were fitted to determine the capacity of the resistance potential to predict AMR in Enterobacterales infections in each setting. The most informative model accurately predicted the numbers of resistant infections in the target populations for 14/14 of antibiotics in the UK, 12/12 in Kenya, and 9/12 in Cambodia. Intermittent metagenomics of pooled human samples could represent a powerful pragmatic and economical approach for determining and monitoring AMR in clinical infections, especially in resource-limited settings.
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测序深度对宏基因组样本推断分类组成和AMR基因含量的影响
DOI: 10.1101/593301
发表时间: 2019
期刊: --
影响因子: --
作者:
Gweon H
通讯作者: Gweon H