Græsbøll Kaare, Nielsen Søren Saxmose, Toft Nils, Christiansen Lasse Engbo
Department of Applied Mathematics and Computer Science, Technical University of Denmark, Lyngby, Denmark.
Department of Large Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
PLoS One. 2014 Jul 9;9(7):e100458. doi: 10.1371/journal.pone.0100458. eCollection 2014.
More than 30% of E. coli strains sampled from pig farms in Denmark over the last five years were resistant to the commonly used antimicrobial tetracycline. This raises a number of questions: How is this high level sustained if resistant bacteria have reduced growth rates? Given that there are multiple susceptible and resistant bacterial strains in the pig intestines, how can we describe their coexistence? To what extent does the composition of these multiple strains in individual pigs influence the total bacterial population of the pig pen? What happens to a complex population when antimicrobials are used? To investigate these questions, we created a model where multiple strains of bacteria coexist in the intestines of pigs sharing a pen, and explored the parameter limits of a stable system; both with and without an antimicrobial treatment. The approach taken is a deterministic bacterial population model with stochastic elements of bacterial distributions and transmission. The rates that govern the model are process-oriented to represent growth, excretion, and uptake from environment, independent of herd and meta-population structures. Furthermore, an entry barrier and elimination process for the individual strains in each pig were implemented. We demonstrate how competitive growth between multiple bacterial strains in individual pigs, and the transmission between pigs in a pen allow for strains of antimicrobial resistant bacteria to persist in a pig population to different extents, and how quickly they can become dominant if antimicrobial treatment is initiated. The level of spread depends in a non-linear way of the parameters that govern excretion and uptake. Furthermore, the sampling of initial distributions of strains and stochastic transmission events give rise to large variation in how homogenous and how resistant the bacterial population becomes. Most important: resistant bacteria are demonstrated to survive with a disadvantage in growth rate of well over 10%.
在过去五年中，从丹麦养猪场采集的大肠杆菌菌株中，超过30% 对常用抗菌药物四环素具有抗性。这引发了一系列问题：如果耐药细菌的生长速度降低，这种高抗性水平是如何维持的？鉴于猪肠道中存在多种易感和耐药菌株，我们如何描述它们的共存情况？个体猪体内这些多种菌株的组成在多大程度上影响猪圈中的细菌总数？使用抗菌药物时，复杂的菌群会发生什么变化？为了研究这些问题，我们创建了一个模型，其中多种细菌菌株共存于共用一个猪圈的猪的肠道中，并探索了稳定系统的参数极限；包括有无抗菌治疗的情况。所采用的方法是一个具有细菌分布和传播随机因素的确定性细菌种群模型。控制该模型的速率以过程为导向，代表生长、排泄和从环境中的摄取，与猪群和种群结构无关。此外，还实施了每头猪体内各菌株的进入屏障和清除过程。我们展示了个体猪体内多种细菌菌株之间的竞争性生长，以及猪圈中猪之间的传播如何使抗菌耐药菌株在猪群中以不同程度持续存在，以及如果开始抗菌治疗它们能多快成为优势菌株。传播水平以一种非线性方式取决于控制排泄和摄取的参数。此外，菌株初始分布的采样和随机传播事件导致细菌种群的均匀性和抗性程度产生很大差异。最重要的是：已证明耐药细菌在生长速度上有超过10% 的劣势情况下仍能存活。
