Interactions of antifungal agents with the host immune system are important for understanding the efficacy of these drugs, mainly in patients with impairment of host immune responses, such as renal transplant recipients, in which invasive fungal infections (IFIs) are difficult to eradicate. Therefore, in these patients successful resolution of fungal infections is often related to the ability of the patient’s immune system to cooperate with drugs. The aim of the present study was to evaluate the potential effect of caspofungin on phagocytosis and intracellular killing by PMNs harvested from healthy donors and renal transplant recipients, against Candida albicans and C.glabrata, two of the most common life-threatening fungal pathogens in immunocompromised hosts. PMNs were separated from venous blood samples of 40 healthy donors and 65 renal transplant recipients. The effects of caspofungin on either phagocytosis or intracellular killing by PMNs towards C. albicans and C. glabrata were investigated by incubating yeast cells and PMNs with 1xMIC caspofungin. Drug-free controls were included. A diminished phagocytic efficiency was found in PMNs from renal transplant recipients, with reduced both phagocytosis and fungicidal activity towards intracellular yeasts, in comparison with healthy donor PMNs. As the majority of systemically acting antifungal drugs, caspofungin did not affect phagocytosis by phagocytes. Conversely, the fungicidal activity of PMNs from patients with chronic renal failure was significantly improved by caspofungin, mainly after 60 and 90 min of incubation, in comparison with caspofungin-free controls (p<0.01). The findings of this study show that caspofungin is able to reset the depressed intracellular killing of PMNs from renal transplant recipients, and suggest that caspofungin possesses interesting beneficial properties which make it suitable for the treatment of IFIs in patients with altered phagocyte-dependent innate immunity characterized by high morbidity and mortality.
Effects of caspofungin on Candida albicans and C. glabrata in renal transplant recipients
BANCHE, Giuliana;ALLIZOND, VALERIA;SCALAS, Daniela;MERLINO, Chiara;ROANA, Janira;TULLIO, Viviana Cristina;MANDRAS, Narcisa;CUFFINI, Annamaria
2010-01-01
Abstract
Interactions of antifungal agents with the host immune system are important for understanding the efficacy of these drugs, mainly in patients with impairment of host immune responses, such as renal transplant recipients, in which invasive fungal infections (IFIs) are difficult to eradicate. Therefore, in these patients successful resolution of fungal infections is often related to the ability of the patient’s immune system to cooperate with drugs. The aim of the present study was to evaluate the potential effect of caspofungin on phagocytosis and intracellular killing by PMNs harvested from healthy donors and renal transplant recipients, against Candida albicans and C.glabrata, two of the most common life-threatening fungal pathogens in immunocompromised hosts. PMNs were separated from venous blood samples of 40 healthy donors and 65 renal transplant recipients. The effects of caspofungin on either phagocytosis or intracellular killing by PMNs towards C. albicans and C. glabrata were investigated by incubating yeast cells and PMNs with 1xMIC caspofungin. Drug-free controls were included. A diminished phagocytic efficiency was found in PMNs from renal transplant recipients, with reduced both phagocytosis and fungicidal activity towards intracellular yeasts, in comparison with healthy donor PMNs. As the majority of systemically acting antifungal drugs, caspofungin did not affect phagocytosis by phagocytes. Conversely, the fungicidal activity of PMNs from patients with chronic renal failure was significantly improved by caspofungin, mainly after 60 and 90 min of incubation, in comparison with caspofungin-free controls (p<0.01). The findings of this study show that caspofungin is able to reset the depressed intracellular killing of PMNs from renal transplant recipients, and suggest that caspofungin possesses interesting beneficial properties which make it suitable for the treatment of IFIs in patients with altered phagocyte-dependent innate immunity characterized by high morbidity and mortality.
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