Casolari Chiara, Rossi Tiziana, Baggio Giosué, Coppi Andrea, Zandomeneghi Ginevra, Ruberto Antonio Ippazio, Farina Claudio, Fabio Giuliana, Zanca Andrea, Castelli Mario
Department of Medicine Laboratory, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy.
Pharmacol Res. 2004 Dec;50(6):605-10. doi: 10.1016/j.phrs.2004.06.008.
Candidiasis and cryptococcosis are the most common fungal diseases among patients suffering from HIV infection. In the present work we assess whether the combined therapies, proteinase inhibitors and antimycotic drugs, could modify the therapeutic effect of antimycotics. An in vitro study to evaluate the antifungal effect of saquinavir and antimycotic drugs combination on yeast growth was performed. Strains of C. albicans and C. neoformans from HIV-seropositive patients were used. Susceptibility tests of yeasts to amphotericin B, 5-fluorocytosine, miconazole and fluconazole, singly and in combination with saquinavir, were performed in two different media. In the combinations the antimycotic agents and saquinavir were tested at sub-inhibitory concentrations: 0.1-10 microg ml(-1) and 12.50 microg ml(-1), respectively. The fractionary inhibitory concentration (FIC) index was also calculated. The results show that the interaction between saquinavir and all the antimycotic drugs never resulted in antagonism. Fluconazole acts in more synergistic way, no matter which medium is used. The combined therapy miconazole/saquinavir results in synergism, especially in Sabouraud. The total absence of antagonism and the presence of synergism suggest that a combined therapy could be proposed in the treatment of HIV-seropositive patients to reduce side effects, thanks to the use of lower doses of antimycotic drugs.
念珠菌病和隐球菌病是HIV感染患者中最常见的真菌疾病。在本研究中，我们评估蛋白酶抑制剂和抗真菌药物联合治疗是否会改变抗真菌药物的治疗效果。进行了一项体外研究，以评估沙奎那韦与抗真菌药物联合使用对酵母生长的抗真菌作用。使用了来自HIV血清阳性患者的白色念珠菌和新型隐球菌菌株。在两种不同培养基中，分别对酵母进行了两性霉素B、5-氟胞嘧啶、咪康唑和氟康唑单独及与沙奎那韦联合使用的药敏试验。在联合用药中，抗真菌药物和沙奎那韦的测试浓度均为亚抑制浓度：分别为0.1 - 10微克/毫升和12.50微克/毫升。还计算了部分抑菌浓度（FIC）指数。结果表明，沙奎那韦与所有抗真菌药物之间的相互作用从未导致拮抗作用。无论使用哪种培养基，氟康唑的协同作用更强。咪康唑/沙奎那韦联合治疗具有协同作用，尤其是在沙氏培养基中。完全没有拮抗作用且存在协同作用表明，由于使用较低剂量的抗真菌药物，在治疗HIV血清阳性患者时可以采用联合治疗以减少副作用。
