Synergistic Antifungal Effect of Caspofungin and Human Polymorphonuclear Leukocytes (PMNs) from Chronic Haemodialysed Patients and Renal Transplant Recipients against Candida albicans

Background.Invasive fungal infections(IFIs) are difficult to eradicate especially in immunocompromised host: uremic patients are highly susceptible to fungal infections due to impaired phagocyte-dependent host defences. Hence, antifungal drugs that positively influence phagocyte activity may be crucial for IFI resolution. Objectives.The aim of this study was to evaluate the effect of caspofungin, a new echinocandin, on the functions of PMNs from healthy subjects, haemodialysed patients and renal transplant recipients towards Candida albicans. Study design and Methods.PMNs were separated from venous blood samples of 40 healthy donors, 68 haemodialysed patients and 65 renal transplant recipients. The effects of caspofungin on either phagocytosis or intracellular killing by PMNs towards C.albicans were investigated by incubating yeasts and PMNs with caspofungin. Drug-free controls were included. Results.A diminished PMN efficiency was found in haemodialysed patient and renal transplant recipient PMNs, 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 uremic patient PMNs was significantly potentiated by caspofungin after 60’and 90’ of incubation, in comparison with drug-free controls(p<0.01). Conclusions.Our findings provide evidence that caspofungin is able to restore the depressed intracellular killing by uremic patient PMNs, 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.