Objectives. Taking into account that in immunocompromised patients successful resolution of fungal infections is often related to the ability of the patient’s immune system to cooperate with drugs, this study aimed to evaluate the potential immunomodulating activity exerted by caspofungin on polymorphonuclear cells (PMNs) from chronic hemodialyzed (HDs) and renal transplant patients (RTRs) against Candida glabrata, the most common life-threatening fungal pathogen in such immunocompromised hosts. Methods. PMNs were separated from venous blood samples of HDs and RTRs. The effects of caspofungin on either phagocytosis of radiolabelled C. glabrata fluconazole and voriconazole resistant strain or intracellular fungal killing by PMNs were investigated by incubating yeasts and phagocytes for 30, 60, 90 minutes with caspofungin at MIC level. Caspofungin-free controls were included. Results. A diminished phagocytic efficiency was found in PMNs from HDs and RTRs, with both reduced phagocytosis and fungicidal activity towards intracellular C. glabrata, in comparison with that of healthy donor PMNs. As the majority of systemically acting antifungal drugs, caspofungin did not affect phagocytosis by granulocytes. Conversely, the fungicidal activity of PMNs from HDs and RTRs was significantly (p<0.01) improved by caspofungin, resulting in increased numbers of killed yeasts for all three incubation times compared with those of the drug-free controls: during the 90 minute period the intracellular blastoconidial load was reduced by 56-68% for HDs and by 58-71% for RTRs. Conclusion. In neutropenic high risk patients an empirical use of caspofungin has been described in literature. We previously demonstrated that caspofungin had beneficial properties in enhancing microbicidal functions of PMNs from healthy subjects. The data of this study indicate that caspofungin possesses interesting immunomodulating properties that make it highly suitable for the treatment of C. glabrata multidrug-resistant infections in patients with impaired components of the immune system.
Role of caspofungin in enhancing chronic haemodialysed and kidney transplant patient PMN response against Candida glabrata
ALLIZOND, VALERIA;BANCHE, Giuliana;TULLIO, Viviana Cristina;SCALAS, Daniela;MERLINO, Chiara;MANDRAS, Narcisa;ROANA, Janira;CUFFINI, Annamaria
2011-01-01
Abstract
Objectives. Taking into account that in immunocompromised patients successful resolution of fungal infections is often related to the ability of the patient’s immune system to cooperate with drugs, this study aimed to evaluate the potential immunomodulating activity exerted by caspofungin on polymorphonuclear cells (PMNs) from chronic hemodialyzed (HDs) and renal transplant patients (RTRs) against Candida glabrata, the most common life-threatening fungal pathogen in such immunocompromised hosts. Methods. PMNs were separated from venous blood samples of HDs and RTRs. The effects of caspofungin on either phagocytosis of radiolabelled C. glabrata fluconazole and voriconazole resistant strain or intracellular fungal killing by PMNs were investigated by incubating yeasts and phagocytes for 30, 60, 90 minutes with caspofungin at MIC level. Caspofungin-free controls were included. Results. A diminished phagocytic efficiency was found in PMNs from HDs and RTRs, with both reduced phagocytosis and fungicidal activity towards intracellular C. glabrata, in comparison with that of healthy donor PMNs. As the majority of systemically acting antifungal drugs, caspofungin did not affect phagocytosis by granulocytes. Conversely, the fungicidal activity of PMNs from HDs and RTRs was significantly (p<0.01) improved by caspofungin, resulting in increased numbers of killed yeasts for all three incubation times compared with those of the drug-free controls: during the 90 minute period the intracellular blastoconidial load was reduced by 56-68% for HDs and by 58-71% for RTRs. Conclusion. In neutropenic high risk patients an empirical use of caspofungin has been described in literature. We previously demonstrated that caspofungin had beneficial properties in enhancing microbicidal functions of PMNs from healthy subjects. The data of this study indicate that caspofungin possesses interesting immunomodulating properties that make it highly suitable for the treatment of C. glabrata multidrug-resistant infections in patients with impaired components of the immune system.
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