他汀类降血脂药物对曲霉的体外抗真菌作用

In vitro effects of lovastatin and simvastatin against clinical isolates of Aspergillus species

目的观察降血脂药物洛伐他汀、辛伐他汀对曲霉体外抗真菌活性，以及它们与唑类抗真菌药、两性霉素B的联合抗曲霉作用。方法分别用纸片扩散法和微量液基稀释法，测定洛伐他汀、辛伐他汀对烟曲霉、黄曲霉、土曲霉和黑曲霉的抗菌活性。用纸片扩散法、琼脂扩散联合Etest法测两种药物与伊曲康唑、伏立康唑、两性霉素B的联合抗曲霉作用。结果纸片扩散法显示洛伐他汀、辛伐他汀有体外抗曲霉活性。洛伐他汀、辛伐他汀对烟曲霉的最低抑菌浓度（MIC）范围分别为8．128μg／mL、4～64μg／mL；最低杀菌浓度（MFC）与MIC的差异在2个稀释度内。对于非烟曲霉，48h时，20μg洛伐他汀或辛伐他汀不能产生清晰抑菌圈。洛伐他汀、辛伐他汀对黄曲霉的MIC分别为128μg／mL和64μg／mL；两者对土曲霉和黑曲霉的MIC均〉256μg／mL。洛伐他汀、辛伐他汀与伊曲康唑、伏立康唑、两性霉素B均无协同作用。结论在体外，洛伐他汀、辛伐他汀有抗曲霉活性；但与唑类抗真菌药、两性霉素B无协同作用。

Objective To evaluate the in vitro activity of lovastatin and simvastatin, alone or in combination with azoles or amphotericin B against clinical isolates of Aspergillus species. Methods The antifungal activities of both statins against A. fumigatus, A. flavus, A. terreus, and A. niger strains were tested with disk diffusion assay and standard broth microdilution method. The interactive effects between the statins and itraconazole, voriconazole and amphotericin B against Aspergillus spp. were examined with disk diffusion assay, and agar dilution plus E-test methods, respectively. Results As demonstrated by disk diffusion method, lovastatin and simvastatin were active against Aspergillus spp.. The MIC ranges of lovastatin and simvastatin at 48 h were 8-128 μg/mL and 4-64μg/mL, respectively, and the difference between their MFCs and MICs was within 2-fold dilution. However, 20μg of either of the statins could not produce clear inhibition zone against non-fumigatus aspergillus. The MICs of lovastatin and simvastatin at 48 h were 128 μg/mL and 64 μg/mL against A. flavus, respectively, and 〉 256 μg/mL against both A. terreus and A. niger. No synergism was observed in the effects against Aspergillus spp. between the statins and itraconazole, voriconazole or amphotericin B. Conclusions Both lovastatin and simvastatin are active against Aspergillus spp., and there is no synergism between them and azoles or amphotericin B in this effect.