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具有协变量依赖混合权重的多元正态混合模型的贝叶斯估计及其在抗菌药物耐药性监测中的应用

Bayesian estimation of multivariate normal mixtures with covariate-dependent mixing weights, with an application in antimicrobial resistance monitoring.

作者信息

Jaspers Stijn, Komárek Arnošt, Aerts Marc

机构信息

Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, BE3590, Diepenbeek, Belgium.

Department of Probability and Mathematical Statistics, Faculty of Mathematics and Physics, Charles University, CZ-186, 75 Praha 8-Karln, Czech Republic.

出版信息

Biom J. 2018 Jan;60(1):7-19. doi: 10.1002/bimj.201600253. Epub 2017 Sep 12.

Abstract

Bacteria with a reduced susceptibility against antimicrobials pose a major threat to public health. Therefore, large programs have been set up to collect minimum inhibition concentration (MIC) values. These values can be used to monitor the distribution of the nonsusceptible isolates in the general population. Data are collected within several countries and over a number of years. In addition, the sampled bacterial isolates were not tested for susceptibility against one antimicrobial, but rather against an entire range of substances. Interest is therefore in the analysis of the joint distribution of MIC data on two or more antimicrobials, while accounting for a possible effect of covariates. In this regard, we present a Bayesian semiparametric density estimation routine, based on multivariate Gaussian mixtures. The mixing weights are allowed to depend on certain covariates, thereby allowing the user to detect certain changes over, for example, time. The new approach was applied to data collected in Europe in 2010, 2012, and 2013. We investigated the susceptibility of Escherichia coli isolates against ampicillin and trimethoprim, where we found that there seems to be a significant increase in the proportion of nonsusceptible isolates. In addition, a simulation study was carried out, showing the promising behavior of the proposed method in the field of antimicrobial resistance.

摘要

对抗菌药物敏感性降低的细菌对公众健康构成重大威胁。因此,已设立大型项目来收集最低抑菌浓度(MIC)值。这些值可用于监测一般人群中不敏感分离株的分布情况。数据在多个国家经过数年收集。此外,所采集的细菌分离株并非仅针对一种抗菌药物进行敏感性测试,而是针对一整套物质进行测试。因此,人们感兴趣的是分析两种或更多种抗菌药物的MIC数据的联合分布,同时考虑协变量可能产生的影响。在这方面,我们提出了一种基于多元高斯混合的贝叶斯半参数密度估计程序。混合权重允许依赖于某些协变量,从而使用户能够检测例如随时间的某些变化。这种新方法应用于2010年、2012年和2013年在欧洲收集的数据。我们研究了大肠杆菌分离株对氨苄青霉素和甲氧苄啶的敏感性,发现不敏感分离株的比例似乎有显著增加。此外,还进行了一项模拟研究,结果表明所提出的方法在抗菌药物耐药性领域具有良好的表现。

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