Division of Pediatric Infectious Diseases, Department of Pediatrics Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina.
Division of Pediatric Infectious Diseases, Department of Pediatrics Infectious Diseases Service, Department of Medicine Institute of Microbiology, Lausanne University Hospital, Switzerland.
Clin Infect Dis. 2015 Dec 1;61 Suppl 6:S669-77. doi: 10.1093/cid/civ725.
The antifungal "paradoxical effect" has been described as the reversal of growth inhibition at high doses of echinocandins, most usually caspofungin. This microbiological effect appears to be a cellular compensatory response to cell wall damage, resulting in alteration of cell wall content and structure as well as fungal morphology and growth. In vitro studies demonstrate this reproducible effect in a certain percentage of fungal isolates, but animal model and clinical studies are less consistent. The calcineurin and Hsp90 cell signaling pathways appear to play a major role in regulating these cellular and structural changes. Regardless of the clinical relevance of this paradoxical growth effect, understanding the specific actions of echinocandins is paramount to optimizing their use at either standard or higher dosing schemes, as well as developing future improvements in our antifungal arsenal.
抗真菌“矛盾效应”被描述为棘白菌素类药物（最常见的是卡泊芬净）高剂量时生长抑制作用的逆转。这种微生物学效应似乎是细胞对细胞壁损伤的一种代偿性反应，导致细胞壁成分和结构以及真菌形态和生长的改变。体外研究在一定比例的真菌分离物中证实了这种可重复的效应，但动物模型和临床研究的结果则不太一致。钙调神经磷酸酶和热休克蛋白 90 细胞信号通路似乎在调节这些细胞和结构变化中发挥着主要作用。无论这种矛盾生长效应的临床相关性如何，了解棘白菌素类药物的具体作用对于优化其在标准或更高剂量方案下的使用以及开发我们抗真菌武器库的未来改进至关重要。
