摘要翻译：
细菌种群对杀菌剂或抗生素处理的耐受性在生物膜和浮游环境中都有很好的记录。然而，对于产生这种耐受的机制仍然知之甚少。越来越多的证据表明，小的、非突变的细菌亚群不受抗生素挑战的影响，并为典型剂量方案的失败提供了一个有吸引力的解释。尽管一个剂量挑战可以杀死所有的易感细菌，但剩下的姊妹细胞可以作为种群再生的来源。我们给出了一般恒化器模型周期加药失效的鲁棒条件，它支持了更早的、更专业的批处理模型的数学结论和模拟。我们的情况意味着治疗方案在全球范围内是失败的，因为混合细菌种群最终会持续超过一个独立于种群初始组成的水平。我们还给出了治疗成功的充分条件，至少对于接近稳定状态的初始种群组成，对应于细菌清除。最后，我们研究了细菌被消灭的速度如何取决于抗生素给药的持续时间。我们发现这种依赖性不一定是单调的，这意味着最佳剂量不一定对应于抗生素的连续给药。因此，真正的周期性方案在治疗各种各样的细菌感染方面更有优势。
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英文标题：
《Failure of antibiotic treatment in microbial populations》
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作者：
Patrick De Leenheer and Nick Cogan
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最新提交年份：
2008
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分类信息：

一级分类：Quantitative Biology        数量生物学
二级分类：Populations and Evolution        种群与进化
分类描述：Population dynamics, spatio-temporal and epidemiological models, dynamic speciation, co-evolution, biodiversity, foodwebs, aging; molecular evolution and phylogeny; directed evolution; origin of life
种群动力学；时空和流行病学模型；动态物种形成；协同进化；生物多样性；食物网；老龄化；分子进化和系统发育；定向进化；生命起源
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一级分类：Quantitative Biology        数量生物学
二级分类：Other Quantitative Biology        其他定量生物学
分类描述：Work in quantitative biology that does not fit into the other q-bio classifications
不适合其他q-bio分类的定量生物学工作
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英文摘要：
  The tolerance of bacterial populations to biocidal or antibiotic treatment has been well documented in both biofilm and planktonic settings. However, there is still very little known about the mechanisms that produce this tolerance. Evidence that small, non-mutant subpopulations of bacteria are not affected by antibiotic challenge has been accumulating and provides an attractive explanation for the failure of typical dosing protocols. Although a dosing challenge can kill all the susceptible bacteria, the remaining persister cells can serve as a source of population regrowth. We give a robust condition for the failure of a periodic dosing protocol for a general chemostat model, which supports the mathematical conclusions and simulations of an earlier, more specialized batch model. Our condition implies that the treatment protocol fails globally, in the sense that a mixed bacterial population will ultimately persist above a level that is independent of the initial composition of the population. We also give a sufficient condition for treatment success, at least for initial population compositions near the steady state of interest, corresponding to bacterial washout. Finally, we investigate how the speed at which the bacteria are wiped out depends on the duration of administration of the antibiotic. We find that this dependence is not necessarily monotone, implying that optimal dosing does not necessarily correspond to continuous administration of the antibiotic. Thus, genuine periodic protocols can be more advantageous in treating a wide variety of bacterial infections.
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PDF链接：
https://arxiv.org/pdf/0807.1943