Hughes Josie, Huo Xi, Falk Lindsey, Hurford Amy, Lan Kunquan, Coburn Bryan, Morris Andrew, Wu Jianhong
Centre for Disease Modelling, York University, Toronto, Ontario, Canada.
Department of Mathematics, Ryerson University, Toronto, Ontario, Canada.
PLoS One. 2017 Feb 9;12(2):e0171218. doi: 10.1371/journal.pone.0171218. eCollection 2017.
Sequential antimicrobial de-escalation aims to minimize resistance to high-value broad-spectrum empiric antimicrobials by switching to alternative drugs when testing confirms susceptibility. Though widely practiced, the effects de-escalation are not well understood. Definitions of interventions and outcomes differ among studies. We use mathematical models of the transmission and evolution of Pseudomonas aeruginosa in an intensive care unit to assess the effect of de-escalation on a broad range of outcomes, and clarify expectations. In these models, de-escalation reduces the use of high-value drugs and preserves the effectiveness of empiric therapy, while also selecting for multidrug-resistant strains and leaving patients vulnerable to colonization and superinfection. The net effect of de-escalation in our models is to increase infection prevalence while also increasing the probability of effective treatment. Changes in mortality are small, and can be either positive or negative. The clinical significance of small changes in outcomes such as infection prevalence and death may exceed more easily detectable changes in drug use and resistance. Integrating harms and benefits into ranked outcomes for each patient may provide a way forward in the analysis of these tradeoffs. Our models provide a conceptual framework for the collection and interpretation of evidence needed to inform antimicrobial stewardship.
序贯性抗菌药物降阶梯治疗旨在通过在检测确认药敏后换用其他药物，尽量减少对高价值广谱经验性抗菌药物的耐药性。尽管该方法已广泛应用，但其降阶梯治疗的效果仍未得到充分理解。不同研究对干预措施和结果的定义有所不同。我们使用重症监护病房中铜绿假单胞菌传播和进化的数学模型，评估降阶梯治疗对一系列结果的影响，并明确预期。在这些模型中，降阶梯治疗减少了高价值药物的使用，保留了经验性治疗的有效性，同时也选择了多重耐药菌株，使患者易受定植和二重感染。我们模型中降阶梯治疗的净效应是增加感染患病率，同时也增加有效治疗的概率。死亡率变化很小，可能为正也可能为负。感染患病率和死亡等结果的微小变化的临床意义可能超过药物使用和耐药性方面更容易检测到的变化。将危害和益处纳入每个患者的排序结果中，可能为分析这些权衡提供一条前进的道路。我们的模型为收集和解释抗菌药物管理所需的证据提供了一个概念框架。
