Invasive fungal infections (IFIs) are difficult to eradicate especially in immunocompromised host: chronic haemodialysed patients and renal transplant recipients are highly susceptible to fungal opportunistic infections characterized by high morbidity and mortality, due to impaired phagocyte-dependent host defences. Hence, antifungal drugs with immune-enhancing properties that positively influence phagocyte activity may be crucial for resolution of fungal infections. The aim of this study was to evaluate the effects exerted by caspofungin, a new echinocandin, on the functions of PMNs from healthy subjects, haemodialysed patients and renal transplant recipients towards Candida albicans, the most common life-threatening fungal pathogen in immunocompromised hosts.
PMNs were separated from venous blood samples of 40 healthy donors, 68 chronic haemodialysed patients and 65 renal transplant recipients. The effects of caspofungin on either phagocytosis of radiolabelled C.albicans or intracellular fungal killing by PMNs were investigated by incubating yeasts and phagocytes for 30,60, and 90 min with caspofungin at MIC level. Caspofungin-free controls were included.
Based on in vitro results, a diminished phagocytic efficiency was found in PMNs from haemodialysed patients and renal transplant recipients, with reduced both phagocytosis and fungicidal activity towards intracellular yeasts, in comparison with healthy subject PMNs. As the majority of systemically acting antifungal drugs, caspofungin did not significantly improve phagocytic activity. Conversely, the fungicidal activity of PMNs from immunocompromised patients was significantly potentiated by caspofungin, mainly after 60 and 90 min of incubation, in comparison with caspofungin-free controls (p<0.01).
Our findings provide evidence that caspofungin at MIC level is able to restore the depressed intracellular killing by PMNs from haemodialysed patients and renal transplant recipients, through a synergistic effect with PMNs towards C.albicans and may constitute effective therapeutic option for IFIs treatment in patients with altered phagocyte-dependent innate immunity.
