When the investigated strains were sensitive to both compounds

When the investigated strains were sensitive to both compounds Panobinostat cost of the combination, additive interactions were frequently noticed. Synergistic interactions were observed in many cases when a strain was sensitive only to the azole compound (as in certain combinations with ATO or ROS) or the statin compound (as in certain combinations with FLU). In many combinations with an additive effect, the concentrations of drugs needed for total growth inhibition could be decreased by

several dilution steps. Similar interactions were observed when the variability of the within-species sensitivities to some selected drug combinations was investigated. The number of immunocompromised individuals with an enhanced susceptibility to opportunistic fungal infections has increased significantly in recent decades (Singh, 2001). These mycoses are predominantly caused by Candida and Aspergillus species Ku-0059436 in vivo (Walsh & Groll, 1999), but the incidence of infections due to zygomycetous fungi has also risen (Kauffman, 2004; Chayakulkeeree et al., 2006). As the treatment of these fungal infections is frequently hampered by the lack of an efficient antifungal agent, there is increasing interest in the application of combination antifungal therapy. Coadministration of two or three antifungal

compounds may improve the efficacy of the treatment, and extends the spectrum of activity; furthermore, resistance also may be avoided and toxicity reduced using lower concentrations of the chemotherapeutic agents (Nosanchuk, 2006). As a result, a number of studies have focused on the antifungal activity of nonantifungal drugs, and on the Cyclin-dependent kinase 3 development of efficient antifungal combination therapy involving such compounds (Afeltra & Verweij, 2003; Galgóczy et al., 2009a). Statins are used to reduce the cholesterol level in the blood. They are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which catalyzes a rate-limiting step in the acetate–mevalonate pathway of the terpenoid biosynthesis

(Liao & Laufs, 2005). Statins were originally identified as secondary metabolites of fungi, and various natural, chemically modified and synthetic compounds are now available commercially, including lovastatin (LOV), pravastatin (PRA), simvastatin (SIM), fluvastatin (FLV), atorvastatin (ATO) and, most recently, rosuvastatin (ROS) and pitavastatin (Schachter, 2005). Statins are currently used for hyperlipidemia control and protection from cardiovascular events, but they have other pleiotropic properties, including anti-inflammatory, immunomodulatory and antioxidant effects (Liao & Laufs, 2005). In addition, there is increasing evidence for the potential use of statins in preventing and treating infections (Falagas et al., 2008; Galgóczy et al., 2009b), as they attenuate the pathogenicity of microorganisms, modulating the signaling and other regulatory pathways involved in controlling infection (Sun & Singh, 2009).

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