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

• Published in: International journal of antimicrobial agents Vol. 39; no. 1; pp. 73 - 76
• Main Authors: Scalas, Daniela, Banche, Giuliana, Merlino, Chiara, Giacchino, Franca, Allizond, Valeria, Garneri, Giuseppe, Patti, Rosaria, Roana, Janira, Mandras, Narcisa, Tullio, Vivian, Cuffini, Anna Maria
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.01.2012; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibiotics. Antiinfectious agents. Antiparasitic agents; antifungal agents; Antifungal Agents - immunology; Antifungal Agents - pharmacology; Antifungal Agents - therapeutic use; antifungal properties; Biological and medical sciences; blood; Candida albicans; Candida albicans - drug effects; Candida albicans - immunology; Candidiasis - drug therapy; Candidiasis - immunology; Caspofungin; cell-mediated immunity; Drug Synergism; Echinocandins - immunology; Echinocandins - pharmacology; Echinocandins - therapeutic use; Emergency and intensive care: renal failure. Dialysis management; Female; Haemodialysis patients; Humans; Immunity, Innate - drug effects; Immunity, Innate - immunology; Infectious Disease; Intensive care medicine; Intracellular killing; kidney diseases; Kidney Failure, Chronic - therapy; Lipopeptides; Male; Medical sciences; Microbial Sensitivity Tests; Middle Aged; minimum inhibitory concentration; mortality; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - pathology; patients; phagocytes; Phagocytosis; Phagocytosis - drug effects; Phagocytosis - immunology; Pharmacology. Drug treatments; PMNs; Polymorphonuclear cells; Renal Dialysis; synergism; therapeutics; yeasts; Intracellular killing; Candida albicans; Haemodialysis patients; Polymorphonuclear cells; PMNs; Caspofungin; Phagocytosis; Human; Yeast; Hemodialysis; Granulocyte; Natural immunity; Patient; In vitro; Echinocandine derivatives; Fungi; Antifungal agent; Chronic; Fungi Imperfecti; Intracellular; Neutrophil; Cell; Phagocyte
• ISSN: 0924-8579; 1872-7913; 1872-7913
• DOI: 10.1016/j.ijantimicag.2011.09.015

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.