| BackgroundThe incidence of fungal infection in the worldwide, especially Candida infections, has increased dramatically in the past decades as results of the extensive use of glucocorticoid, broad-spectrum antibiotics, immunosuppressive and antitumordrugs, wide launching of organ transplantation and interventional treatment technology, and increasing diseases of diabetes and AIDS. However, effective and safe antifungal drugs are very scarce in clinics. At the same time, along with the large dose and long-term therapeutic and prophylactic use of antifungal drugs, fungal resistance increased rapidly, especially the azole resistant is more and more serious, which brought new difficulties to clinical diagnosis and treatment. Therefore, looking for new antifungal drugs is a hot focus of researching works at present. Sertraline is a selective5-serotonin reuptake inhibitors, commonly used in depression, obsessive-compulsive disorder, premenstrual syndrome, and so on. Ten years ago, Lass-Florl C and his partners found that sertraline has a certain inhibitory effect on Candida and Aspergillus, and carried on the preliminary discussion about the antifungal mechanism. Then the antifungal effect of sertraline began to be concerned. This study investigates the anti-Candida albicans activity of sertraline in vitro by use of CLSI-M27-A microdilution method and checkerboard microdilution method.ObjectiveTo determine the anti-Candida albicans activity of sertraline in vitro and the combined effect of sertraline with itraconazole, fluconazole or amphotericin B, so as to set up the foundation for clarifying antifungal mechanism and creat new idea for fungal infection treatment.Methods1. One hundred and thirty-two Candida strains were isolated from varieties of clinical specimens and then identified by examining with10%KOH for microscopical examination, culturing on Sabouraud-chloramphenicol glucose agar, germ tube test, chlamydospore test, and culturing on CHROMagar, respectively.2. The minimum inhibitory concentration (MIC) of sertraline, fluconazole, amphotericin B and itraconazole to103clinically isolated Candida albicans were tested by CLSI-M27-A microdilution method, meanwhile fluconazole and amphotericin B used as quality control drugs.3. The checkerboard microdilution method was applied to assay the combination effect of sertraline with fluconazole, amphotericin B or itraconazole for18strains of Candida albicans.Results1. Of total132isolates, the results of identification are as follows:103(78.03%) strains of C.albicans,7(5.30%) C.krusei,9(6.82%) C.parapsilosis,2(1.51%) C.tropicalis,10(7.58%) C.glabrata, and1(0.76%) C.guilliermondii.2. Sertraline has inhibitory effect on Candida albicans tested, and its range of MICs are3.715-59.375μg/ml, mean MICs22.097μg/ml.3. Synergistic and no interaction are observed obviously, without antagonism in the combination effect of sertraline with fluconazole. The mean fractional inhibitory concentration index (FICI) between fluconazole-susceptible and-resistant Candidas albicans is no significant difference (P=0.285)4.Sertraline have influence on itraconazole, amphotericin B or fluconazole against Candida albicans, and the range of FICIs are0.3-1.0,0.3-1.5, and0.2-1.0, respectively, meanwhile there are no significant difference on the influence (P=0.738).Conclusions1. Most of the Candida stains isolated from clinical patients of Candida infection are Candida albicans.2. Sertraline has antifungal effects on medically important Candida albicans.3. The interactions between sertraline and fluconazole are mainly synergistic effects, and this interaction in fluconazole-susceptible and-resistant Candidas albicans is no significant difference.4.Synergistic effects are main interactions between sertraline with fluconazole, amphotericin B or itraconazole against Candida albicans, and the interactions is no significant difference. |
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