Focussing on resistance to front-line drugs is the most effective way to combat the antimicrobial resistance crisis
Focussing on resistance to front-line drugs is the most effective way to combat the antimicrobial resistance crisis
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关注一线药物耐药性是应对抗菌药物耐药性危机的最有效途径
DOI：
10.1101/498329
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Perry M
中科院分区：
文献类型：
--
作者：
Perry M
在与抗菌素耐药性（AMR）相关的医学、科学和政治领域，目前人们高度关注使最后一线抗菌素治疗无效的多重耐药病原体。 我们质疑目前对最后一线抗菌药物耐药性的关注，认为解决对一线抗菌药物的耐药性具有更大的公共卫生效益。利用来自欧洲的25种药物-病原体组合的AMR监测数据，我们发现一线病原体耐药性的存在引发了一系列耐药性选择，最终导致病原体对最后一线抗菌药物的耐药性。然后，我们通过模拟耐药性演变的动态来询问，AMR战略应对中的3项关键干预措施是否更有效地针对一线或最后一线治疗。 我们表明，通过使用抗菌药物佐剂或一线耐药诊断或引入新型一线抗菌药物使一线治疗更有效的干预措施，与在最后一线治疗中实施的相同干预措施相比，均可导致死亡率和发病率的更大降低。 在一线感染管理中大规模使用一种新发现的抗菌剂，以最大限度地提高其公共卫生效益，这与现行政策背道而驰，但可能为药物开发商提供有价值的激励。我们证明，资金，出版物和对这些出版物的关注并没有反映一线抗菌药物的重要性，并且不成比例地用于最后一线抗菌药物，占抗菌药物处方的不到10%。虽然研究对最后一线药物的耐药性无疑很重要，但我们的工作向公共卫生机构、资助机构和研究人员传达了一个强烈的信息，即将资源分配给一线感染可能是对抗抗菌素耐药性危机的更有效方法。
In medical, scientific and political arenas relating to antimicrobial resistance (AMR) there is currently an intense focus on multi-drug resistant pathogens that render last-line antimicrobial treatments ineffective. We question the current emphasis of attention on resistance to last-line antimicrobials, arguing that tackling resistance to front-line antimicrobials has a greater public health benefit. Using AMR monitoring data on 25 drug-pathogen combinations from across Europe, here we show that the presence of front-line pathogen resistance initiates a cascade of resistance selection that ultimately leads to pathogen resistance to last-line antimicrobials. We then interrogate, by modelling the dynamics of resistance evolution, whether 3 key interventions in the strategic response to AMR are more effectively targeted at front-line or last-line treatment. We show that interventions that make front-line therapy more effective by use of antimicrobial adjuvants or front-line resistance diagnostics or by introduction of a novel, front-line antimicrobial all lead to a larger reduction in mortality and morbidity than the same interventions implemented in last-line therapy. Mass use of a newly discovered antimicrobial in front-line infection management to maximise its public health benefit is contrary to current policy but may provide valuable incentives for drug developers. We demonstrate that funding, publications, and attention to those publications do not reflect the importance of front-line antimicrobials and are disproportionately devoted to last-line antimicrobials that account for less than 10% of antimicrobial prescriptions. While studying resistance to last-line drugs is undoubtedly important, our work relays a strong message to public health agencies, funding bodies, and researchers that allocating resources to front-line infections can be a more effective way to combat the antimicrobial resistance crisis.
一个有效的系统，用于β-内酰胺抗生素的细胞内递送以克服细菌耐药性。
影响因子：
4.6
作者：
Abed N;Saïd-Hassane F;Zouhiri F;Mougin J;Nicolas V;Desmaële D;Gref R;Couvreur P
通讯作者：
Couvreur P
估计美国抗生素耐药性旁观者选择的比例
DOI：
--
发表时间：
2018
期刊：
bioRxiv
影响因子：
--
作者：
C. Tedijanto;S. Olesen;Y. Grad;M. Lipsitch
通讯作者：
M. Lipsitch