国产两性霉素B脂质体对侵袭性真菌病病原菌体外抗菌活性的研究

In Vitro Antibacterial Activity of Domestic Liposomal Amphotericin Bagainst Pathogenic Bacteria of Invasive Mycosis

目的:评估国产、进口注射用两性霉素B脂质体(liposomal amphotericin B,L-AmB)制剂、两性霉素B脱氧胆酸盐(amphotericin B deoxycholate,Am BD)制剂与Am B标准品体外抗真菌活性的一致性,并观察多种Am B制剂对侵袭性真菌的体外药物敏感性,以期为临床抗真菌治疗提供依据。方法:参照美国临床实验室标准化协会(Clinical and Laboratory Standards Institute,CLSI)的标准文件M27-ED4和M38-ED3测定4种Am B制剂对393株侵袭性真菌病原菌的最低抑菌浓度(minimum inhibitory concentration,MIC),并使用统计分析软件进行数据分析处理。结果:以进口注射用L-Am B的MIC值为参照,国产注射用L-Am B在多数受测菌种的基本一致性(essential agreement,EA)为100%,在热带念珠菌与近平滑念珠菌中EA分别为98%和95%。4种Am B制剂对大多数受测菌株的MIC值均≤2μg/ml。2种L-Am B注射制剂在烟曲霉、黄曲霉、黑曲霉中MIC略低于Am B标准品与注射用Am BD制剂,但在部分希木龙念珠菌、土曲霉、镰刀菌、构巢曲霉中的MIC值为16μg/ml,高于Am B标准品和注射用Am BD制剂。结论:国产与进口L-Am B注射制剂的抗菌活性一致性较高。对大部分临床分离真菌来说,L-AmB制剂和非脂质体试剂体外抗真菌活性较强。目前,L-Am B对部分希木龙念珠菌、土曲霉等特定真菌菌种体外药敏试验的抗真菌活性降低,但机制尚不清楚,仍需进一步研究。

Objective:To evaluate the consistency of in vitro antifungal activity of domestic and imported liposomal amphotericin B(L-AmB)reagent for injection,common preparation of amphotericin B deoxycholate(AmBD)for injection and standard AmB.To observe the in vitro drug susceptibility of various AmB preparations to invasive fungi so as to provide evidence for clinical antifungal therapy.Methods:The minimum inhibitory concentrations(MICs)of 4 AmB preparations against 393 invasive fungal pathogens were determined in parallel with reference to the standard documents M27-ED4 and M38-ED3 of the American Clinical and Laboratory Standards Institute(CLSI).Data were analyzed using statistical analysis software.Results:Taking the MIC value of imported L-AmB for injection as a reference,the essential agreement(EA)of domesticL-AmB for injection was 100%in most tested strains.EA in Candida parapsilosis was 98%and 95%.The MICs values of the four AmB formulations against most of the tested strains were all≤2μg/ml.The MICs of the two liposome preparations in Aspergillus fumigatus,Aspergillus flavus,and Aspergillus niger were slightly lower than those of the standard and common injection preparations,and the MICs values in some Candida haemulonii,Aspergillus terreus,Fusarium,and Aspergillus nidulans were 16μg/ml,significantly higher than the standard and common injection preparations.Conclusion:The in vitro drug susceptibility consistency rate of domestic and imported L-AmB preparations for injection is relatively high.Liposome preparations and non-liposome preparations shown high activity in vitro against most clinically isolated fungi.At present,the antifungal activity of L-AmB against some specific fungal species,such as Candida haemulonii and Aspergillus terreus,is decreased in vitro susceptibility tests,but the mechanism is still unclear and further studies are needed.