Caspofungin efficacy in re-establishing chronic haemodialyzed and renal transplant patient phagocyte primary functions against Candida albicans and C. glabrata infections.

Background. Although invasive fungal infections attributed to Candida spp., particularly to C. albicans, are prevalent, a tendency of an increasing proportion of C. non-albicans species has also been reported: the most important species is C. glabrata. Due to the impaired phagocyte-dependent host defences, patients with chronic renal failure are more frequently at risk of candidiasis than healthy subjects (HSs). Thus, for candidiasis resolution immunomodulating antifungal drugs may be decisive. This study aimed to evaluate the potential immunomodulating activity exerted by caspofungin on polymorphonuclear cells (PMNs) from haemodialysed patients (HDs) and renal transplant recipients (RTRs), compared with HSs, towards both C. albicans and multidrug-resistant C. glabrata. Study design and Methods. PMNs were separated from venous blood samples of 66 HDs, 54 RTRs and 30 HSs. The effects of caspofungin on both phagocytosis and intracellular killing by PMNs towards Candida spp. were investigated by incubating yeasts and PMNs with caspofungin at MIC values. Drug-free controls were included. Results. A reduced fungicidal activity towards intracellular C. albicans and C. glabrata, was detected in HD-PMNs and RTR-PMNs, in comparison with HS-PMNs. This decreased PMN antibacterial activity was re-estabilished by the addition of caspofungin that significantly improved the intracellular killing of HD-PMNs and RTR-PMNs against both C.albicans and C.glabrata, without affecting phagocytosis. Conclusions. These data provide confirmation that caspofungin in addition to its antifungal activity possesses immunomodulating properties that make it highly suitable for the treatment of infections caused by both C. albicans and multidrug-resistant C. glabrata in patients with altered phagocyte-dependent innate immunity which represent a high risk population.