Due to the impaired phagocyte-dependent host defenses, patients with chronic renal failure are more frequently at risk of candidiasis than healthy subjects (HSs). Candida albicans remains the most commonly isolated species, but current epidemiological trends indicate a progressive shift towards the spread of non-albicans Candida spp., particularly Candida glabrata. Since synergism between innate immunity and antifungal drugs may be crucial for candidiasis resolution, this study focuses on the effects exerted by caspofungin on functional activities of polymorphonuclear cells (PMNs) from haemodialysed patients (HDs) and renal transplant recipients (RTRs), compared with HSs, towards both C. albicans and C. glabrata. PMNs were separated from venous blood samples of 66 HDs, 54 RTRs and 30 HSs. The influence of caspofungin on both phagocytosis and intracellular killing by PMNs towards Candida spp. were investigated by incubating yeasts and PMNs with caspofungin at MIC and sub-MIC values. Drug-free controls were included. In the antifungal-free test condition, 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 was detected in HD-PMNs and RTR-PMNs, in comparison with HS-PMNs. The addition of caspofungin significantly improved the intracellular killing of HD-PMNs and RTR-PMNs against both C. albicans and C. glabrata. These findings provide corroboration that caspofungin, in addition to its antifungal activity, exerts a synergistic effect on phagocytes that make it highly suitable for the treatment of infections caused by both Candida spp. in patients with altered phagocyte-dependent innate immunity which represent a high risk population. As the therapeutic efficacy of antifungal drugs appears to be limited without the help of host immune reactivity, this synergistic drug effect on host phagocyte cells could be relevant to patients receiving caspofungin for either prophylaxis or therapeutic purposes.
USO DELLA CASPOFUNGINA NEL TRATTAMENTO DI CANDIDOSI NEI PAZIENTI EMODIALIZZATI E TRAPIANTATI RENALI: RIPRISTINO DELLA RIDOTTA CAPACITÀ FAGOCITARIA
BANCHE, Giuliana;MANDRAS, Narcisa;ROANA, Janira;TULLIO, Viviana Cristina;ALLIZOND, VALERIA;SCALAS, Daniela;MERLINO, Chiara;CUFFINI, Annamaria
2012-01-01
Abstract
Due to the impaired phagocyte-dependent host defenses, patients with chronic renal failure are more frequently at risk of candidiasis than healthy subjects (HSs). Candida albicans remains the most commonly isolated species, but current epidemiological trends indicate a progressive shift towards the spread of non-albicans Candida spp., particularly Candida glabrata. Since synergism between innate immunity and antifungal drugs may be crucial for candidiasis resolution, this study focuses on the effects exerted by caspofungin on functional activities of polymorphonuclear cells (PMNs) from haemodialysed patients (HDs) and renal transplant recipients (RTRs), compared with HSs, towards both C. albicans and C. glabrata. PMNs were separated from venous blood samples of 66 HDs, 54 RTRs and 30 HSs. The influence of caspofungin on both phagocytosis and intracellular killing by PMNs towards Candida spp. were investigated by incubating yeasts and PMNs with caspofungin at MIC and sub-MIC values. Drug-free controls were included. In the antifungal-free test condition, 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 was detected in HD-PMNs and RTR-PMNs, in comparison with HS-PMNs. The addition of caspofungin significantly improved the intracellular killing of HD-PMNs and RTR-PMNs against both C. albicans and C. glabrata. These findings provide corroboration that caspofungin, in addition to its antifungal activity, exerts a synergistic effect on phagocytes that make it highly suitable for the treatment of infections caused by both Candida spp. in patients with altered phagocyte-dependent innate immunity which represent a high risk population. As the therapeutic efficacy of antifungal drugs appears to be limited without the help of host immune reactivity, this synergistic drug effect on host phagocyte cells could be relevant to patients receiving caspofungin for either prophylaxis or therapeutic purposes.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
