M-1585. Antifungal Effects of Triazoles and Caspofungin Combined with Human Neutrophils (PMNs) against Hyphae of Different Zygomycetes
Session: Poster Session: Fungal Immunopathogenesis
Sunday, October 26, 2008: 12:00 AM
Room: Hall C
Background: Zygomycetes, such as Rhizopus oryzae (RO), Rhizopus microsporus (RM) and Cunninghamella bertholletiae (CB), cause severe morbidity and high mortality in immunocompromised hosts. PMNs have critical role in innate antifungal immunity against these pathogens. Some antifungal agents are known to enhance PMN response against Aspergillus fumigatus. We therefore studied whether PMNs in combination with voriconazole (VRC), posaconazole (PSC) and caspofungin (CAS) demonstrate enhanced damage to hyphae of RO, RM and CB. Methods: 105 sporangiospores/ml of RO, RM, and CB were incubated in RPMI at 37oC for 7, 9 and 9h, respectively, in order to yield similar biomass as measured by spectrophotometry. PMNs were isolated from healthy volunteers by dextran sedimentation/ficoll centrifugation. Concentration for triazoles was 0.5mg/L and for CAS 0.1mg/L. PMNs were added to hyphae at effector cell-to-target ratio 5:1. Antifungal agents were added alone or in combination with PMNs and incubated at 37oC/5%CO2 for 2h. Percent hyphal damage (HD) was assessed by XTT assay. Statistical analysis was performed using ANOVA with Dunnett post-test and unpaired Mann-Whitney test (n=5-7). Results: PMN-induced HD against the three species ranged from 31-45%. CB was less susceptible than either Rhizopus sp. (31% vs 37% or 46% for CB vs RM or RO p<0.05). The HD induced by VRC, PSC or CAS against CB and RO and by CAS against RM ranged from 18-29%, while both triazoles showed no effect against RM hyphae at the concentration used. Neither antagonistic nor synergistic effects were observed with the combination of PMNs and any of the agents against RO, RM or CB.
Conclusions: While PMNs possess substantial activity against these zygomycetes, the activity of VRC, PSC and CAS against hyphae is variable. The combination of these agents with PMNs was neither antagonistic nor synergistic.
Elpiniki Georgiadou, Aristotle University od Thessaloniki, Emmanuel Roilides, PhD, Hippokration Hospital, Thessaloniki, Greece, Maria Simitsopoulou, PhD, Aristotle Univ., Thessaloniki, Greece, Thomas Walsh, MD, FIDSA, National Cancer Institute, Bethesda, MD and  M. Simitsopoulou, None.


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