Predicting the antistaphylococcal effects of daptomycin-rifampicin combinations in an in vitro dynamic model.,The Journal of Antibiotics

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Predicting the antistaphylococcal effects of daptomycin-rifampicin combinations in an in vitro dynamic model.
The Journal of Antibiotics ( IF 2.1 ) Pub Date : 2019-10-17 , DOI: 10.1038/s41429-019-0249-x
Maria V Golikova ₁ , Elena N Strukova ₁ , Yury A Portnoy ₁ , Stephen H Zinner ₂ , Alexander A Firsov ₁

Affiliation

To predict the effects of combined use of antibiotics on their pharmacodynamics, the susceptibility of Staphylococcus aureus to daptomycin-rifampicin combinations was tested at concentration ratios equal to the ratios of daptomycin and rifampicin 24-h areas under the concentration-time curve (AUC24s) simulated in an in vitro dynamic model. In combination with rifampicin, daptomycin MICs decreased 2- to 31-fold, whereas rifampicin MICs were similar with or without daptomycin. The enhanced susceptibility of S. aureus to daptomycin combined with rifampicin resulted in both an increase of the actual AUC24/MIC ratios and also more pronounced antibacterial effects compared with single treatments. The areas between the control growth and time-kill curves (ABBCs) determined in combined and single daptomycin treatments were plotted against AUC24/MIC on the same graph (r2 0.90). These findings suggest that the effects of daptomycin-rifampicin combinations can be predicted by AUC24/MICs of daptomycin using its MIC determined at pharmacokinetically derived daptomycin-to-rifampicin concentration ratios.

中文翻译：

在体外动力学模型中预测达托霉素-利福平组合的抗葡萄球菌作用。

为了预测抗生素联合使用对其药效的影响，在模拟的浓度-时间曲线（AUC24s）下，以等于达托霉素和利福平24小时面积之比的浓度比，测试了金黄色葡萄球菌对达托霉素-利福平组合的敏感性。在体外动力学模型中。与利福平合用时，达托霉素MIC降低2到31倍，而有或没有达托霉素时，利福平MIC则相似。与单药治疗相比，金黄色葡萄球菌对达托霉素与利福平联合使用的敏感性增加，导致实际AUC24 / MIC比值增加，并且产生更明显的抗菌作用。在同一张图上，将联合和单次达托霉素治疗中确定的对照生长曲线和时间杀灭曲线（ABBC）之间的面积相对于AUC24 / MIC作图（r2 0.90）。这些发现表明达托霉素-利福平组合的作用可以通过达托霉素的AUC24 / MIC来预测，其使用在药代动力学上得出的达托霉素与利福平浓度比确定的MIC来测定。

更新日期：2020-01-16

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