Lepak Alexander J, Zhao Miao, Berkow Elizabeth L, Lockhart Shawn R, Andes David R
Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, USA.
Antimicrob Agents Chemother. 2017 Jul 25;61(8). doi: 10.1128/AAC.00791-17. Print 2017 Aug.
is an emerging multidrug-resistant threat. The pharmacodynamics of three antifungal classes against nine strains was explored using a murine invasive candidiasis model. The total drug median pharmacodynamic (PD) target associated with net stasis was a fluconazole AUC/MIC (the area under the concentration-time curve over 24 h in the steady state divided by the MIC) of 26, an amphotericin B /MIC (maximum concentration of drug in serum divided by the MIC) of 0.9, and a micafungin AUC/MIC of 54. The micafungin PD targets for were ≥20-fold lower than those of other species in this animal model. Clinically relevant micafungin exposures produced the most killing among the three classes.
是一种新出现的多重耐药威胁。使用小鼠侵袭性念珠菌病模型探索了三类抗真菌药物对九种菌株的药效学。与净停滞相关的总药物中位药效学（PD）靶点为：氟康唑的AUC/MIC（稳态下24小时浓度-时间曲线下面积除以MIC）为26，两性霉素B的Cmax/MIC（血清中药物最大浓度除以MIC）为0.9，米卡芬净的AUC/MIC为54。在该动物模型中，米卡芬净对[具体物种未给出]的PD靶点比其他[具体物种未给出]物种低≥20倍。临床相关的米卡芬净暴露在这三类药物中产生的杀菌效果最佳。
