Abstract

Background:

Antimicrobial resistance (AMR) is one of the most significant health threats to society. A growing body of research demonstrates selection for AMR likely occurs at environmental concentrations of antibiotics. However, no standardized experimental approaches for determining selective concentrations of antimicrobials currently exist, preventing appropriate environmental and human health risk assessment of AMR.

Objectives:

We aimed to design a rapid, simple, and cost-effective novel experimental assay to determine selective effect concentrations of antibiotics and to generate the largest experimental data set of selective effect concentrations of antibiotics to date.

Methods:

Previously published methods and data were used to validate the assay, which determines the effect concentration based on reduction of bacterial community (wastewater) growth. Risk quotients for test antibiotics were generated to quantify risk.

Results:

The assay (SELection End points in Communities of bacTeria, or the SELECT method) was used to rapidly determine selective effect concentrations of antibiotics. These were in good agreement with quantitative polymerase chain reaction effect concentrations determined within the same experimental system. The SELECT method predicted no effect concentrations were minimally affected by changes in the assay temperature, growth media, or microbial community used as the inoculum. The predicted no effect concentrations for antibiotics tested ranged from $0.05\mathrm{\mu }\mathrm{g}/\mathrm{L}$ for ciprofloxacin to $\mathrm{1,250}\mathrm{\mu }\mathrm{g}/\mathrm{L}$ for erythromycin.

Discussion:

The lack of evidence demonstrating environmental selection for AMR, and of associated human health risks, is a primary reason for the lack of action in the mitigation of release of antibiotics into the aquatic environment. We present a novel method that can reliably and rapidly fill this data gap to enable regulation and subsequent mitigation (where required) to lower the risk of selection for, and human exposure to, AMR in aquatic environments. In particular, ciprofloxacin and, to a lesser extent, azithromycin, cefotaxime, and trimethoprim all pose a significant risk for selection of AMR in the environment. https://doi.org/10.1289/EHP6635

中文翻译：

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“细菌群落的选择终点”（SELECT）方法：一种新型实验方法，可促进环境中抗菌素耐药性选择的风险评估

摘要

背景：

抗菌素耐药性（AMR）是对社会最重大的健康威胁之一。越来越多的研究表明，对AMR的选择可能发生在环境浓度的抗生素下。但是，目前尚无用于确定抗菌素选择性浓度的标准化实验方法，从而无法对AMR进行适当的环境和人类健康风险评估。

目标：

我们旨在设计一种快速，简单且具有成本效益的新型实验测定法，以确定抗生素的选择性作用浓度，并生成迄今为止最大的抗生素选择性作用浓度的实验数据集。

方法：

先前发布的方法和数据用于验证测定，该测定基于细菌群落（废水）生长的减少来确定效应浓度。产生测试抗生素的风险商以量化风险。

结果：

该测定法（细菌群落中的选择终点，或SELECT方法）用于快速确定抗生素的选择性作用浓度。这些与同一实验系统中确定的定量聚合酶链反应效应浓度高度吻合。SELECT方法预测，用作接种物的测定温度，生长培养基或微生物群落的变化不会对影响浓度产生最小的影响。预计测试的抗生素无作用浓度范围为$0.05\mathrm{\mu }\mathrm{G}/\mathrm{大号}$ 环丙沙星 $\mathrm{1,250}\mathrm{\mu }\mathrm{G}/\mathrm{大号}$ 用于红霉素。

讨论：

缺乏证明对AMR进行环境选择以及相关的人类健康风险的证据，是缺乏缓解抗生素向水生环境释放的行动的主要原因。我们提出了一种新颖的方法，该方法可以可靠，迅速地填补这一数据空白，从而能够进行监管和后续缓解措施（在需要时），以降低在水生环境中选择AMR和人类接触AMR的风险。特别是环丙沙星，以及在较小范围内的阿奇霉素，头孢噻肟和甲氧苄啶都对在环境中选择AMR构成重大风险。https://doi.org/10.1289/EHP6635