抗真菌药物单独和联合应用对曲霉体外药敏试验研究

目的:探讨两性霉素B(AmB)、特比萘芬(TBF)、伊曲康唑(ICZ)、氟胞嘧啶(5-FC)和氟康唑(FCZ)在单独和联合用药时对曲霉的敏感性.方法:应用美国临床实验室标准化委员会制定的M38-A方案,单独用药时AmB、TBF和ICZ取100%生长抑制为最小抑菌浓度(MiC),5-FC和FCZ取50%生长抑制为最小抑菌浓度,联合用药时取100%生长抑制为最小抑菌浓度,以部分抑菌浓度(FIC)来判定药物间的相互作用,药物间的相互作用解释为FIC≤0.5为协同作用,0.5＜FIC≤1.0为相加作用,1.0＜FIC≤2.0为无关作用,FIC＞2.0为拮抗作用.结果:TBF对烟曲霉的MIC值明显高于黄曲霉和黑曲霉,ICZ对黄曲霉的MIC值较低,AmB对黑曲霉的MIC值较低,而对黄曲霉MIC值较高,差异具有统计学意义.TBF联合ICZ、AmB联合ICZ对曲霉菌属产生较好的协同相加作用.AmB联合TBF对曲霉主要表现为相加作用,5-FC和FCZ与其他药物联合应用对曲霉菌属表现为拮抗和无关作用.结论:单独用药时不同抗真菌药物对曲霉菌种的敏感性具有差异.TBF联合ICZ、AmB联合ICZ在体外对曲霉具有协同和相加作用,其效果优于其他药物的联合应用.

Effects of individual or combined application of antifungal drugs against Aspergillus species: an in vitro study

Objective:To investigate the activities of amphotericin B(AmB),itraconazole(ICZ),terbinafine(TBF),fluconazole (FCZ)and 5-flucytosine(5-FC)against Aspergillus in the individual application or combined application in vitro.Methods:M38-A protocol of NCCLS was employed.At individual application,the minimal inhibitory concentration(MIC)of AmB,TBF and ICZ were determined as 100% growth reduction of fungus compared with the controls,which of FCZ and 5-FC were determined as the growth reduction more than 50%.In combined application.the MICs of all the antifungal agents were determined as 100% growth reduction of fungus.The drug interaction was determined according to the fractional inhibitory con centration(FIC),which was defined as synergic effect a8 the FIC was≤0.50,as additive effect as the FIC between 0.50 and 1.0.as indifierent effect as the FIC between 1.0 and 2.0,and as antagonistic affect as the FIC more than 2.0.Results:A higher MIC value of TBF against Aspergillus fumigatus than that against Aspergillus flavux or Aspergillus nige was seen. An obviously lower MIC value of ICZ against Aspergillus flavus was revealed.A lower MIC value of AmB against Aspergillus nige and higher MIC value of that against Aspergillus flavus were found.Either the combination of ICZ with TBF or the combination of ICZ with AmB was synersic or additive against most Aspergillus species.The combination of TBF with AmB showed additive effect against most species of Aspergillu.The combination of 5-FC with FCZ or with other drugs showed antagonistic effects or indifferent effects.Conclusions:The susceptibilities of different species of A spergillus to individual antifungal agent were different.The combination of ICZ with TBF or ICZ with AmB displays potent synergic or additive effects in vitro against most species of Aspergillus,superior to other combinations of antifungal agents.