Ghannoum M A, Filler S G, Ibrahim A S, Fu Y, Edwards J E
Department of Medicine, Harbor-University of California, Los Angeles Medical Center, Torrance 90509.
Antimicrob Agents Chemother. 1992 Oct;36(10):2239-44. doi: 10.1128/AAC.36.10.2239.
Using an in vitro model of intravascular infection, we examined the effects of exposure to subinhibitory concentrations of fluconazole and amphotericin B on the ability of Candida albicans to adhere to and damage human umbilical vein endothelial cells. Incubation of the organisms for 18 h in 0.5x the MICs of fluconazole and amphotericin B inhibited endothelial cell adherence by 22 and 91%, respectively (P less than 0.001 for each drug). Candida-induced endothelial cell injury was also decreased by exposing the organisms to the antifungal drugs while in contact with the endothelial cells. Fluconazole inhibited damage by approximately 50% at concentrations ranging from 0.25x to 5x the MIC (P less than 0.01 for each concentration). Exposure to amphotericin B at 0.5x the MIC completely blocked the ability of the organisms to injure endothelial cells. The capacities of the antifungal agents to inhibit endothelial cell injury paralleled their abilities to suppress candidal germination. Organisms exposed to up to 5x the MIC of fluconazole had diminished, but still detectable, germ tube production and elongation, whereas incubation in 0.5x the MIC of amphotericin B completely abrogated germination. In addition to their direct effects on the growth of C. albicans, fluconazole and amphotericin B may decrease the ability of the fungus to disseminate hematogenously by inhibiting the organisms' capacity to adhere to and injure endothelial cells.
利用血管内感染的体外模型，我们研究了暴露于亚抑菌浓度的氟康唑和两性霉素B对白色念珠菌黏附及损伤人脐静脉内皮细胞能力的影响。将白色念珠菌在氟康唑和两性霉素B的0.5倍最低抑菌浓度（MIC）中孵育18小时，分别使内皮细胞黏附率降低了22%和91%（每种药物P均小于0.001）。当白色念珠菌与内皮细胞接触时，将其暴露于抗真菌药物中也可减少念珠菌诱导的内皮细胞损伤。氟康唑在0.25倍至5倍MIC浓度范围内可使损伤降低约50%（每种浓度P均小于0.01）。在0.5倍MIC浓度下暴露于两性霉素B可完全阻断白色念珠菌损伤内皮细胞的能力。抗真菌剂抑制内皮细胞损伤的能力与其抑制念珠菌萌发的能力平行。暴露于高达5倍MIC氟康唑的白色念珠菌芽管产生和伸长减少，但仍可检测到，而在0.5倍MIC两性霉素B中孵育则完全消除了萌发。除了对白色念珠菌生长的直接影响外，氟康唑和两性霉素B可能通过抑制白色念珠菌黏附及损伤内皮细胞的能力来降低真菌经血行播散的能力。
