A study on antifungal effects of statins and quinolans and their synergism with antifungal medicines

The reason of high mortality and morbidity rate in invasive fungal infections, widely empiric antifungal use, occurrence of resistant fungal strains and decrease of active antifungal drugs have accelerated new drug researches. Because a dramatic increase of response with new antifungal drugs in fungal infections has not been provided, this has caused to tend treatment option in combination with antifungal drugs and other drugs or agents. Formation of broader action spectrum, enhancement of activity and decrease of the number of resistant microorganism have been anticipated theoretically. Numerous in vitro sensitivity tests examining interections of antifungal drugs with other antimicrobial drugs (quinolon and statin) and animal studies until today have been carried out. The limitatons of implementation to human as a result of these must be certainly taken into consideration. Although nowadays available amphotericin B and fluconazol are the most efficient drugs, serious ocular and systemic toxicity have limited use of the drugs and we encounter a primary important problem of treatment of fungal infections. Also other problem is that factors causing fungal infections increase resistance to antifungal drugs. And therefore especially new antifungal drug searches targeting protein translation mechanisms and DNA topoisomerase enzymes and hydroxymethylglutari coenzyme A (HMG-CoA) reductase have became more of an issue.Moxifloxacin, broder action spectrum (gram-positive, gram-negative, anaerob), effective with topoisomerase 2 and topoisomerase 4 enzyme inhibiton, is a fourth generation quinolon antibiotic. Researches out of ophthalmology field have determined that protective activity of moksifloksasin in fungal infections through immune modulation as well as antibacterial efficacy of it is demonstrated. Although there are also numerous studies regarding synergistic activity with antifungal drugs of other quinolons in literature, there is limited number of studies concerning antifungal activity and relationship with antifungal drugs of moxifloxacin. Atorvastatin that is in a statin group, coenzyme A (HMG-CoA) reductase inhibitors or often with used names `? statines `?, lead among pharmacological agents used for prevention and treatment of cardiovascular diseases. This drugs cause to decrease of endogenic cholesterol by inhibiting partially HMG-CoA reductase which is rate limiting step in cholesterol synthesis and therefore this drugs increase the number of LDL receptors and contribute its catabolism by extraction of LDL . In this study, it is aimed to determine by in vitro whether moxifloxacin and atorvastatin by itself have an antifungal efficacy on C. albicans and synergic activity in combination with amphotericin B or fluconazol. In this study, seven clinical and three reference C. albicans strains are used. Moxifloxacin, atorvastatin, amphotericin B and fluconazol on total ten strains in vitro effects by microplac dilution method and also in combination with amphotericin B-atorvastatin, amphotericin-moxifloxacin, fluconazol-atorvastatin and fluconazol-moxifloxacin by chessboard method are examined.It is determined that alone each of moxifloxacin and atorvastatin have some in vitro antifungal activity according to MIC and to compare control proliferation well. MIC values for both antifungal drugs (amphotericin B and fluconazol) as for combination drugs are low. Although alone amphotericin B and in combination with moksifloksasin or atorvastatin in terms of MIC value are not determined statistically a significant difference; available proliferation is 15% when alone amphotericin B uses; it is not determined any proliferatin in samples as for using amphotericin B in combination with other drugs. While alone use of fluconazol inhibits 65 % of proliferation rate, use of fluconazol in combination with other drugs is 75% of proliferation rate. Therefore it is possible to say that synergistic activity with amphotericin B or fluconazol of moksifloksasin and atorvastatin show. As a result, in this thesis study, it is determined that moxifloxacin and atorvastatin out of antifungal drugs alone have not an antifungal activity in vitro but moxifloxacin and atorvastatin demonstrate a synergistic activity for amphotericin B and fluconazol in combination with amphotericin B or fluconazol.