Shor Erika, Perlin David S, Kontoyiannis Dimitrios P
Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.
Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA.
mSphere. 2025 May 27;10(5):e0016125. doi: 10.1128/msphere.00161-25. Epub 2025 Apr 16.
is a significant public health threat due to its environmental persistence and multidrug resistance, with echinocandins being the preferred treatment. However, in addition to resistance, echinocandin tolerance and heteroresistance may contribute to treatment challenges. Echinocandin tolerance involves reduced drug-mediated killing, while heteroresistance is the ability of a small cell subset to grow at high drug concentrations. These phenomena may facilitate the emergence of full resistance and complicate clinical outcomes. The clinical significance of these mechanisms remains unclear, with limited data correlating them with treatment failures. Research is needed to understand their mechanisms and impact, develop streamlined and robust methods to detect them in clinical settings, and explore mitigation strategies. The pathogen's range of drug adaptations demands innovative approaches like spatial transcriptomics to dissect these complex responses and improve patient outcomes.
由于其环境持久性和多重耐药性,它是一个重大的公共卫生威胁,棘白菌素是首选治疗药物。然而,除了耐药性之外,棘白菌素耐受性和异质性耐药可能会给治疗带来挑战。棘白菌素耐受性涉及药物介导的杀伤作用降低,而异质性耐药是一小部分细胞亚群在高药物浓度下生长的能力。这些现象可能会促进完全耐药的出现并使临床结果复杂化。这些机制的临床意义仍不清楚,将它们与治疗失败相关联的数据有限。需要开展研究来了解它们的机制和影响,开发简化且可靠的方法在临床环境中检测它们,并探索缓解策略。病原体的药物适应范围需要像空间转录组学这样的创新方法来剖析这些复杂反应并改善患者预后。