Objective. Phagocyte-dependent host defences are frequently impaired in patients with chronic renal failure who are particularly exposed to serious microbial infections characterized by high morbidity and mortality. In recent years, the patterns of yeast infections have changed. Previously, Candida albicans was the most prevalent cause of Candida infections, whereas in recent times, other Candida species have become common infection-causing pathogens. C. glabrata has recently emerged as the second most common cause of invasive candidiasis. Since synergism between innate immunity and antifungal drugs may be crucial for candidiasis resolution, this study provides more information on the effects exerted by caspofungin on functionality of polymorphonuclear cells (PMNs) from haemodialysed patients (HDs) and renal transplant recipients (RTRs), compared with healthy subjects (HSs), towards both C. albicans and C. glabrata azole-resistant strain. Methods. PMNs were separated from venous blood samples of 30 HSs, 66 HDs and 54 RTRs. The influence of caspofungin on both phagocytosis and intracellular killing by PMNs towards Candida spp. were investigated by incubating yeasts and PMNs (1:1) with caspofungin at MIC and sub-MIC values. Drug-free controls were included. Results. In the drug-free controls, no significant difference among the phagocytic activity of HD-PMNs, RTR-PMNs and HS-PMNs was detected. In contrast, a reduced fungicidal activity towards intracellular C. albicans and C. glabrata azole-resistant was detected in HD-PMNs and RTR-PMNs, in comparison with HS-PMNs. The addition of caspofungin at MIC and sub-MIC values significantly re-established the impaired HD-PMNs and RTR-PMNs intracellular fungicidal activity against both C. albicans and C. glabrata, by acting both on phagocytes and on yeasts, even those azole-resistant. Conclusion. These findings provide corroboration that caspofungin, in addition to its antifungal activity, shows immunomodulating properties by restoring the deficient activity of PMN from immunocompromised patients. These results make caspofungin highly suitable for the treatment of Candida spp infections in those patients which represent a high risk population because of altered phagocyte-dependent innate immunity.
Successful re-establishment of the impaired uremic patient granulocyte killing activity exerted by caspofungin against Candida species. Accepted as POSTER presentation
BANCHE, Giuliana;ALLIZOND, VALERIA;MANDRAS, Narcisa;SCALAS, Daniela;ROANA, Janira;TULLIO, Viviana Cristina;MERLINO, Chiara;CUFFINI, Annamaria
2013-01-01
Abstract
Objective. Phagocyte-dependent host defences are frequently impaired in patients with chronic renal failure who are particularly exposed to serious microbial infections characterized by high morbidity and mortality. In recent years, the patterns of yeast infections have changed. Previously, Candida albicans was the most prevalent cause of Candida infections, whereas in recent times, other Candida species have become common infection-causing pathogens. C. glabrata has recently emerged as the second most common cause of invasive candidiasis. Since synergism between innate immunity and antifungal drugs may be crucial for candidiasis resolution, this study provides more information on the effects exerted by caspofungin on functionality of polymorphonuclear cells (PMNs) from haemodialysed patients (HDs) and renal transplant recipients (RTRs), compared with healthy subjects (HSs), towards both C. albicans and C. glabrata azole-resistant strain. Methods. PMNs were separated from venous blood samples of 30 HSs, 66 HDs and 54 RTRs. The influence of caspofungin on both phagocytosis and intracellular killing by PMNs towards Candida spp. were investigated by incubating yeasts and PMNs (1:1) with caspofungin at MIC and sub-MIC values. Drug-free controls were included. Results. In the drug-free controls, no significant difference among the phagocytic activity of HD-PMNs, RTR-PMNs and HS-PMNs was detected. In contrast, a reduced fungicidal activity towards intracellular C. albicans and C. glabrata azole-resistant was detected in HD-PMNs and RTR-PMNs, in comparison with HS-PMNs. The addition of caspofungin at MIC and sub-MIC values significantly re-established the impaired HD-PMNs and RTR-PMNs intracellular fungicidal activity against both C. albicans and C. glabrata, by acting both on phagocytes and on yeasts, even those azole-resistant. Conclusion. These findings provide corroboration that caspofungin, in addition to its antifungal activity, shows immunomodulating properties by restoring the deficient activity of PMN from immunocompromised patients. These results make caspofungin highly suitable for the treatment of Candida spp infections in those patients which represent a high risk population because of altered phagocyte-dependent innate immunity.
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