The optimal deployment of synergistic antibiotics: a control-theoretic approach
The optimal deployment of synergistic antibiotics: a control-theoretic approach
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协同抗生素的最佳部署：控制理论方法
DOI：
10.1098/rsif.2012.0279
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发表时间：
2012
影响因子：
3.9
通讯作者：
Peña-Miller R
中科院分区：
文献类型：
--
作者：
Peña-Miller R
医学和药理学界长期以来一直在寻找抗菌药物，当它们联合使用时，这种相互作用被称为协同作用。然而，这些药物组合施加了有利于多药耐药性的选择性压力，因此，协同作用的益处可能在仅仅几代细菌之后就丧失了。此外，有实验证据表明，抗生素治疗可以通过改变肠道致病菌和肠道细菌之间的平衡，使其有利于病原体，从而破坏定植耐药性，并有可能增加感染的风险。因此，我们要问，使用协同药物的最佳方式是什么？我们提出了一个进化模型的真菌和病原菌竞争在一个连续的培养装置的单一限制性碳源的影响下，两种抑菌和协同抗生素。该模型使我们能够评估不同药物部署策略的有效性，并使用最优控制理论的思想，以了解是否存在其他类型的治疗可能优于基于固定剂量多药物组合的治疗的情况。我们的主要结果可以这样说：协同抗生素的最佳部署，以消除病原体的存在下，在我们的模型系统中的细菌不发生组合，但通过部署它们顺序。
Medical and pharmacological communities have long searched for antimicrobial drugs that increase their effect when used in combination, an interaction known assynergism. These drug combinations, however, impose selective pressures in favour of multi-drug resistance and as a result, the benefit of synergy may be lost after only a few bacterial generations. Furthermore, there is experimental evidence that antibiotic treatment can disrupt colonization resistance by shifting the balance between enteropathogenic and commensal bacteria in favour of the pathogens, with the potential to increase the risk of infections. So, we ask, what is the best way of using synergistic drugs? We pose an evolutionary model of commensal and pathogenic bacteria competing in a continuous culture device for a single limiting carbon source under the effect of two bacteriostatic and synergistic antibiotics. This model allows us to evaluate the efficacy of different drug deployment strategies and, using ideas from optimal control theory, to understand whether there are circumstances in which other types of therapy might be favoured over those based on fixed-dose multi-drug combinations. Our main result can be stated thus: the optimal deployment of synergistic antibiotics to remove a pathogen in the presence of commensal bacteria in our model system occurs not in combination, but by deploying them sequentially.
影响因子：
21.1
作者：
W. Greco;G. Bravo;J. C. Parsons
通讯作者：
W. Greco;G. Bravo;J. C. Parsons
抗生素治疗期间耐药性的发展
DOI：
--
发表时间：
1987
期刊：
European Journal of Clinical Microbiology
影响因子：
--
作者：
D. Milatovic;I. Braveny
通讯作者：
I. Braveny
联合治疗：限制耐药性出现的方法？
影响因子：
5.9
作者：
M. Michéa;J. Pechère;B. Marchou;R. Auckenthaler
通讯作者：
R. Auckenthaler