Background

The current situation of critical progression in resistance to more effective antibiotics has forced the reuse of old highly toxic antibiotics and, for several reasons, the extension of the indications of combined antibiotic therapy as alternative options to broad spectrum empirical mono-therapy. A key aspect for selecting an appropriate and adequate antimicrobial therapy is that prescription must be based on local epidemiology and knowledge since many aspects, such as prevalence of microorganisms and effectiveness of antimicrobials, change from hospitals, or even areas and services within a single hospital. Therefore, the selection of combinations of antibiotics requires the application of a methodology that provides objectivity, completeness and reproducibility to the analysis of the detailed microbiological, epidemiological, pharmacological information on which to base a rational and reasoned choice.

Methods

We proposed a methodology for decision making that uses a multiple criteria decision analysis (MCDA) to support the clinician in the selection of an efficient combined empiric therapy. The MCDA includes a multi-objective constrained optimization model whose criteria are the maximum efficacy of therapy, maximum activity, the minimum activity overlapping, the minimum use of restricted antibiotics, the minimum toxicity of antibiotics and the activity against the most prevalent and virulent bacteria. The decision process can be defined in 4 steps: (1) selection of clinical situation of interest, (2) definition of local optimization criteria, (3) definition of constraints for reducing combinations, (4) manual sorting of solutions according to patient's clinical conditions, and (5) selection of a combination.

Experiments and results

In order to show the application of the methodology to a clinical case, we carried out experiments with antibiotic susceptibility tests in blood samples taken during a five years period at a university hospital. The validation of the results consists of a manual review of the combinations and experiments carried out by an expert physician that has explained the most relevant solutions proposed according to current clinical knowledge and their use.

Conclusion

We show that with the decision process proposed, the physician is able to select the best combined therapy according to different criteria such as maximum efficacy, activity and minimum toxicity. A method for the recommendation of combined antibiotic therapy developed on the basis of a multi-objective optimization model may assist the physicians in the search for alternatives to the use of broad-spectrum antibiotics or restricted antibiotics for empirical therapy. The decision proposed can be easily reproduced for any local epidemiology and any different clinical settings.

中文翻译：

---

一种基于多准则决策分析的方法，用于在经验疗法中结合抗生素。

背景

对更有效的抗生素产生耐药性的关键进展的当前状况已迫使旧的高毒性抗生素重新使用，并且由于多种原因，扩大了联合抗生素治疗的适应症作为广谱经验单一疗法的替代选择。选择适当和适当的抗菌药物治疗的一个关键方面是处方必须基于当地的流行病学和知识，因为很多方面，例如微生物的流行和抗菌药物的有效性，医院的变化，甚至单个医院内的区域和服务。因此，选择抗生素组合需要使用一种方法，该方法可为详细的微生物学，流行病学，

方法

我们提出了一种决策方法，该方法使用多准则决策分析（MCDA）来支持临床医生选择有效的联合经验疗法。MCDA包括一个多目标约束优化模型，其标准是治疗的最大功效，最大活性，最小活性重叠，最小限度使用抗生素，最小毒性抗生素以及针对最普遍和最强细菌的活性。决策过程可分为4个步骤定义：（1）选择感兴趣的临床情况；（2）定义局部优化标准；（3）定义减少组合的约束条件；（4）根据患者的临床情况对解决方案进行手动分类条件，以及（5）选择组合。

实验与结果

为了显示该方法在临床病例中的应用，我们对一家大学医院在五年时间内采集的血液样本中的抗生素敏感性试验进行了实验。结果的验证包括由专家医师对组合和实验进行的人工审查，该专家解释了根据当前临床知识及其用途提出的最相关的解决方案。

结论

我们证明，通过提出的决策过程，医生能够根据不同的标准（例如最大的疗效，最大的活性和最小的毒性）选择最佳的联合疗法。在多目标优化模型的基础上开发的推荐联合抗生素治疗的方法可以帮助医生寻找将广谱抗生素或限制性抗生素用于经验治疗的替代方法。对于任何地方流行病学和任何不同的临床环境，可以很容易地重复提出的决定。