Caspofungin benefit on phagocytes from patients with renal dysfunction infected with multidrug-resistant Candida glabrata.

AIM: We evaluated the potential impact of caspofungin (CAS) on the functional activities of polymorphonuclear leukocytes (PMNs) from hemodialyzed patients (HDs) and renal transplant recipients (RTRs) against a multidrug-resistant clinical strain of Candida glabrata compared with those of PMNs from healthy subjects (HSs). MATERIALS & METHODS: Effects of CAS on PMN phagocytosis and intracellular killing towards multidrug-resistant C. glabrata were evaluated in 66 HDs, 54 RTRs and 30 HSs in the absence and presence of CAS at MIC and sub-MICs. RESULTS: When HD PMNs and RTR PMNs were exposed to both MICs and sub-MICs of CAS, their fungicidal activity against the multidrug-resistant C. glabrata strain was significantly higher than that of drug-free controls, with survival index values that overlapped with those achieved by HS PMNs. CONCLUSION: The obtained results underline the role of CAS in the restoration of the impaired PMN functions in HDs and RTRs. CAS might still constitute an effective therapeutic option for the treatment of invasive fungal infections caused by multidrug-resistant C. glabrata in patients with altered phagocyte-dependent innate immunity.

Role of caspofungin in restoring the impaired phagocyte-dependent innate immunity towards Candida albicans in chronic haemodialysis patients.

Phagocyte-dependent cellular immunity in chronic kidney disease patients undergoing haemodialysis treatment is frequently impaired owing to the uraemic state, resulting in an intrinsic susceptibility to developing invasive fungal infections with high mortality rates. 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 (CAS) on the functional activities of polymorphonuclear cells (PMNs) in haemodialysed patients (HDs) towards Candida albicans compared with those of PMNs from healthy subjects (HSs). 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 the presence of CAS at the minimum inhibitory concentration (MIC) and at sub-MICs. CAS-free controls were also included. In the drug-free test condition, no significant difference between the phagocytic activity of HD-PMNs and HS-PMNs was detected. In contrast, a progressive decline in the intracellular killing activity of HD-PMNs against proliferating yeasts was observed. CAS at MIC and sub-MIC levels was able to improve significantly the intracellular fungicidal activity of HD-PMNs against C. albicans, restoring their functionality. These findings provide evidence that CAS exerts a synergistic effect on HD-PMNs against C. albicans, being able to strength the depressed intracellular killing activity. These results corroborate the use of CAS as an effective therapeutic option for the treatment of invasive fungal infections in HDs, in whom even a marginal influence of antifungal drugs on host response may have a relevant effect.

Candida albicans infections in renal transplant recipients: effect of caspofungin on polymorphonuclear cells.

This study aimed to compare the caspofungin immunomodulating activities against Candida albicans on polymorphonuclear cells (PMNs) from renal transplant recipients (RTRs) and healthy subjects (HSs). RTR PMNs showed a significantly reduced fungicidal activity compared with that of HS PMNs. Addition of caspofungin to RTR PMNs significantly potentiated the yeast intracellular killing rate, achieving values similar to those observed for HS PMNs. These data show that caspofungin is suitable for invasive candidiasis treatment in patients with immune system-impaired components.