抗真菌药物对丝状真菌的体外抗菌活性研究

Antifungal activity of anti-fungi drugs against filamentous fungi in vitro

目的了解两性霉素B（AMB）、伊曲康唑（ICZ）、伏立康唑（VRC）和卡泊芬净（CBF）对72株丝状真菌的体外抗菌活性，指导临床合理应用抗真菌药物。方法MIC检测采用美国临床和实验室标准协会（CLSI）制订的用于产丝孢状真菌的体外药敏方案（M38-P）和（M38-A）。AMB、VRC、ICZ在单独用药时分别取100％、100％、≥80％的生长抑制为MIC值，CBF在单独用药时取明确改变真菌菌丝形态的最低浓度作为最小有效浓度。分数抑菌浓度（FIC）评价体外联合效果，FIC=MIC联合／MICA尊Ⅻ＋MIC联合／MICB单独。结果AMB、ICZ、CBF、VRC对72株丝状真菌的MIC90分别为8、4、2、8μg/ml，AMB＋ICZ、AMB＋VRC、ICZ＋VRC联合用药MIC的范围分别为0．125～16．97、0．2452～1．25、0．0625～8．25μg/ml。AMB＋VRC对丝状真菌产生协同作用为20．0％～88．9％，优于AMB＋ICZ的10．0％～62．5％和ICZ＋VRC的20．0％～44．4％（P=0．007〈0．05）。结论72株丝状真菌对4种常用抗真菌药物的体外抗菌活性有差异，AMB＋VRC优于AMB＋ICZ与ICZ＋VRC，同样可作为重症感染治疗的联合用药。

Objective To investigate antifungal activities of AMB, ICZ, VRC, CBF against 72 strains of filamentous fungi in vitro. Methods Based on CLSI M38-P and M38-A scheme, MIC of antifungal drugs were determined. The growing inhibitory concentration of 100% ,100% , ≥80% , for AMB, VRC,ICZ act as respective MIC. For caspofungin, the minimal effective concentration （MEC） was determined as the lowest drug concentration showing morphology change of filaments. The fractional inhibitory concentration （FIC） was used to evaluate the effect of combination therapy. FIC was calculated by the following equation： FIC = MICcombination/MICA drug alone ＋ MICcombination/MICB drug alone. Results MIC90 of AMB, ICZ, CBF, VRC against 72 isolates of filamentous fungi were 8μg/ml, 4 μg/ml, 2μg/ml, 8μg/ml, respectively. MICs range of combined AMB ＋ ICZ, AMB ＋ VRC, ICZ ＋ VRC were 0. 125-16. 97, 0. 2452-1.25, and 0. 0625- 8.25μg/ml respectively. The percent of synergistic interaction of AMB ＋ VRC against filamentous fungi （20. 0%-88. 9% ） was higher than those of AMB ＋ ICZ （ 10. 0%-62.5% ） and ICZ ＋ VRC （20. 0%- 44. 4% ） （ P = 0. 007 〈 0. 05 ）. Conclusions The antifungal activities of four kinds antifungat drugs against 72 strains of filamentous fungi vary in vitro. The therapy of AMB combined with VRC is maybe better than AMB ＋ ICZ and ICZ ＋ VRC for severe fungi infection.