INTRODUCTION: Phagocyte-dependent cellular immunity in chronic kidney disease (CKD) patients under haemodialysis treatment is frequently impaired due to the uremic state, resulting in an intrinsic susceptibility to develope invasive fungal infections with high mortality rates. Candida albicans remains the most frequently isolated species, but current epidemiological trends indicate a progressive shift towards the spread of non-albicans Candida spp., particularly C.glabrata and C.krusei, among haemodialysis patients (HDs). Since synergism between phagocytic cells and antifungal drugs may be crucial for successful therapy, the aim of this study was to evaluate the effects exerted by caspofungin on the functional activities of polymorphonuclear cells (PMNs) in HDs towards both Candida albicans and C.glabrata compared to those of PMNs from healthy subjects (HSs) MATERIALS AND METHODS: PMNs were separated from venous blood samples of 66 HDs and 30 HSs, as controls, and measurement of phagocytic and intracellular fungicidal activities of HD-PMNs and HS-PMNs was performed in presence of caspofungin at the MIC. Caspofungin free-controls were also included. RESULTS: In the drug-free test condition, no significant difference between the phagocytic activity of HD-PMNs and HS-PMNs was detected. On the contrary, a progressive decline in the intracellular killing activity of HD-PMNs against proliferating yeasts was observed. Caspofungin at MIC concentration was able to significantly improve the intracellular fungicidal activity of HD-PMNs against both C.albicans and C.glabrata, without affecting phagocytosis. CONCLUSIONS: Our findings provide evidence that caspofungin exerts a synergistic effect on HD phagocyte cells against both C. albicans and C.glabrata, being able to strength the depressed intracellular killing PMN activity. These results corroborate the use of caspofungin as effective therapeutic option for antifungal treatment in HD patients, in whom even a marginal influence of antifungal drugs on host response may have a relevant effect.
PMN antifungal activity against Candida albicans and C. glabrata is strengthened by caspofungin in chronic haemodialysis patients.
SCALAS, Daniela;MERLINO, Chiara;BANCHE, Giuliana;ALLIZOND, VALERIA;ROANA, Janira;MANDRAS, Narcisa;TULLIO, Viviana Cristina;CUFFINI, Annamaria
2011-01-01
Abstract
INTRODUCTION: Phagocyte-dependent cellular immunity in chronic kidney disease (CKD) patients under haemodialysis treatment is frequently impaired due to the uremic state, resulting in an intrinsic susceptibility to develope invasive fungal infections with high mortality rates. Candida albicans remains the most frequently isolated species, but current epidemiological trends indicate a progressive shift towards the spread of non-albicans Candida spp., particularly C.glabrata and C.krusei, among haemodialysis patients (HDs). Since synergism between phagocytic cells and antifungal drugs may be crucial for successful therapy, the aim of this study was to evaluate the effects exerted by caspofungin on the functional activities of polymorphonuclear cells (PMNs) in HDs towards both Candida albicans and C.glabrata compared to those of PMNs from healthy subjects (HSs) MATERIALS AND METHODS: PMNs were separated from venous blood samples of 66 HDs and 30 HSs, as controls, and measurement of phagocytic and intracellular fungicidal activities of HD-PMNs and HS-PMNs was performed in presence of caspofungin at the MIC. Caspofungin free-controls were also included. RESULTS: In the drug-free test condition, no significant difference between the phagocytic activity of HD-PMNs and HS-PMNs was detected. On the contrary, a progressive decline in the intracellular killing activity of HD-PMNs against proliferating yeasts was observed. Caspofungin at MIC concentration was able to significantly improve the intracellular fungicidal activity of HD-PMNs against both C.albicans and C.glabrata, without affecting phagocytosis. CONCLUSIONS: Our findings provide evidence that caspofungin exerts a synergistic effect on HD phagocyte cells against both C. albicans and C.glabrata, being able to strength the depressed intracellular killing PMN activity. These results corroborate the use of caspofungin as effective therapeutic option for antifungal treatment in HD patients, in whom even a marginal influence of antifungal drugs on host response may have a relevant effect.
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