Cicali Brian, Schmidt Stephan, Zeitlinger Markus, Brown Joshua D
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA.
Department of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.
Pharmaceutics. 2022 Mar 25;14(4):704. doi: 10.3390/pharmaceutics14040704.
Macrolide antibiotics have received criticism concerning their use and risk of treatment failure. Nevertheless, they are an important class of antibiotics and are frequently used in clinical practice for treating a variety of infections. This study sought to utilize pharmacoepidemiology methods and pharmacology principles to estimate the risk of macrolide treatment failure and quantify the influence of their pharmacokinetics on the risk of treatment failure, using clinically reported drug-drug interaction data. Using a large, commercial claims database (2006-2015), inclusion and exclusion criteria were applied to create a cohort of patients who received a macrolide for three common acute infections. Furthermore, an additional analysis examining only bacterial pneumonia events treated with macrolides was conducted. These criteria were formulated specifically to ensure treatment failure would not be expected nor influenced by intrinsic or extrinsic factors. Treatment failure rates were 6% within the common acute infections and 8% in the bacterial pneumonia populations. Regression results indicated that macrolide AUC changes greater than 50% had a significant effect on treatment failure risk, particularly for azithromycin. In fact, our results show that decreased or increased exposure change can influence failure risk, by 35% or 12%, respectively, for the acute infection scenarios. The bacterial pneumonia results were less significant with respect to the regression analyses. This integration of pharmacoepidemiology and clinical pharmacology provides a framework for utilizing real-world data to provide insight into pharmacokinetic mechanisms and support future study development related to antibiotic treatments.
大环内酯类抗生素在其使用及治疗失败风险方面受到了批评。尽管如此，它们仍是一类重要的抗生素，在临床实践中经常用于治疗各种感染。本研究旨在利用药物流行病学方法和药理学原理，通过临床报告的药物相互作用数据，估计大环内酯类治疗失败的风险，并量化其药代动力学对治疗失败风险的影响。利用一个大型商业索赔数据库（2006 - 2015年），应用纳入和排除标准，建立了一个接受大环内酯类药物治疗三种常见急性感染的患者队列。此外，还进行了一项仅检查接受大环内酯类药物治疗的细菌性肺炎事件的额外分析。这些标准是专门制定的，以确保治疗失败不是由内在或外在因素预期或影响的。常见急性感染中的治疗失败率为6%，细菌性肺炎人群中的治疗失败率为8%。回归结果表明，大环内酯类药物的曲线下面积（AUC）变化大于50%对治疗失败风险有显著影响，尤其是阿奇霉素。事实上，我们的结果表明，暴露量的减少或增加变化分别可使急性感染情况下的失败风险增加35%或12%。关于回归分析，细菌性肺炎的结果不太显著。药物流行病学和临床药理学的这种整合提供了一个框架，用于利用真实世界的数据来深入了解药代动力学机制，并支持未来与抗生素治疗相关的研究发展。
