Abstract：
Antibiotic stewardship is hindered by a lack of consideration for complicated environmental fate of antibiotics and their role in resistance development, while the current methodology of eco-toxicological risk assessment has not been fully protective against their potential to select for antibiotic resistance. To address this problem, we established a novel methodologic framework to perform comprehensive environmental risk assessment of antibiotics in terms of resistance development, which was based on selection effect, phenotype resistance level, heteroresistance frequency, as well as prevalence and stability of antibiotic resistance genes. We tracked the contribution of antibiotic load reduction to the mitigation of environmental risk of resistance development by fate and transport modeling. The method was instantiated in a lake-river network-basin complex system, taking the Taihu Basin as a case study. Overall, antibiotic load posed no eco-toxicological risk but an average medium-level environmental risk for resistance development in Taihu Lake. The effect of antibiotic load on resistance risk was both seasonal-dependent and category-dependent, while quinolones posed the greatest environmental risk for resistance development. Mass-flow analysis indicated that temporal-spatial variation in hydrological regime and antibiotic fate together exerted a significant effect on antibiotic load in the system. By apportioning antibiotic load to riverine influx, we identified the hotspots for load reduction and predicted the beneficial response of resistance risk under load-reduction scenarios. Our study proposed a risk-oriented strategy of basin-scaled antibiotic load reduction for environmental risk control of resistance development.
摘要：
缺乏对抗生素复杂的环境命运及其在耐药性发展中的作用的考虑，阻碍了抗生素的管理。虽然目前的生态毒理学风险评估方法尚未完全保护它们选择抗生素耐药性的潜力。为了解决这个问题,我们建立了一个新的方法学框架，在耐药性发展方面对抗生素进行全面的环境风险评估，这是基于选择效应，表型抗性水平，异质电阻频率，以及抗生素抗性基因的流行和稳定性。我们通过命运和运输模型跟踪了减少抗生素负荷对缓解耐药性发展的环境风险的贡献。该方法在湖泊-河流网络-流域复杂系统中进行了实例化，以太湖流域为例。总的来说,抗生素负荷对太湖抗性发展没有生态毒理学风险，但平均具有中等水平的环境风险。抗生素负荷对耐药风险的影响既是季节依赖性的，也是类别依赖性的，而喹诺酮类药物对耐药性发展构成最大的环境风险。质量流量分析表明，水文状况和抗生素命运的时空变化对系统中的抗生素负荷产生了显着影响。通过将抗生素负荷分配给河流涌入，我们确定了负荷降低的热点，并预测了负荷降低方案下阻力风险的有益反应。我们的研究提出了以风险为导向的流域规模抗生素负荷降低策略，以控制耐药性发展的环境风险。
