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Pharmacodynamic and immunological interactions of amphotericin B formulations and voriconazole with human neutrophils against mature Scedosporium apiospermum and Fusarium spp. biofilms.
J Antimicrob Chemother. 2023 Apr 03; 78(4):1076-1083.JA

Abstract

BACKGROUND

Mould infections caused by Scedosporium apiospermum and Fusarium solani species complex (FSSC) biofilms are rising among immunocompromised and immunocompetent patients. Little is known about the immunomodulatory effects of antifungal agents against these moulds. We examined the effects of deoxycholate and liposomal amphotericin B (DAmB, LAmB) and voriconazole on antifungal activities and immune responses of neutrophils (PMNs) against mature biofilms compared with their planktonic counterparts.

METHODS

Antifungal activity of human PMNs exposed to mature biofilms and planktonic cells for 24 h was determined at effector-to-target ratios of 2:1 and 5:1, alone or combined with DAmB, LAmB and voriconazole, assessed as fungal damage by XTT assay. Cytokine production was evaluated by multiplex ELISA, following PMN stimulation with biofilms in the presence/absence of each drug.

RESULTS

All drugs showed additive or synergistic effects with PMNs against S. apiospermum at 0.03-32 mg/L. They showed antagonism primarily against FSSC at 0.06-64 mg/L. Increased IL-8 was produced by PMNs exposed to S. apiospermum biofilms plus DAmB or voriconazole compared with PMNs exposed to biofilms alone (P < 0.01). During combined exposure, IL-1β was increased, an effect only counteracted by increased levels of IL-10 caused by DAmB (P < 0.01). LAmB and voriconazole caused similar IL-10 levels with those released by biofilm-exposed PMNs.

CONCLUSIONS

The synergistic, additive or antagonistic effects of DAmB, LAmB or voriconazole on biofilm-exposed PMNs are organism-specific, with FSSC exhibiting greater resilience than S. apiospermum to antifungals. Biofilms of both moulds caused dampened immune responses. The drug-mediated immunomodulating effect on PMNs, evidenced by IL-1β, enhanced host protective functions.

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Authors+Show Affiliations

Vikelouda K
Infectious Diseases Unit, 3rd Department Pediatrics, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki and Hippokration General Hospital, Thessaloniki, Greece.
Simitsopoulou M
Infectious Diseases Unit, 3rd Department Pediatrics, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki and Hippokration General Hospital, Thessaloniki, Greece. Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Antachopoulos C
Infectious Diseases Unit, 3rd Department Pediatrics, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki and Hippokration General Hospital, Thessaloniki, Greece.
Skoura L
Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece. Department of Microbiology, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki and AHEPA University Hospital, Thessaloniki, Greece.
Roilides E
Infectious Diseases Unit, 3rd Department Pediatrics, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki and Hippokration General Hospital, Thessaloniki, Greece. Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.

MeSH

HumansAmphotericin BVoriconazoleAntifungal AgentsFusariumScedosporiumInterleukin-10NeutrophilsFungiBiofilms

Pub Type(s)

Journal Article

Language

eng

PubMed ID

36848199

Citation

Vikelouda, Katerina, et al. "Pharmacodynamic and Immunological Interactions of Amphotericin B Formulations and Voriconazole With Human Neutrophils Against Mature Scedosporium Apiospermum and Fusarium Spp. Biofilms." The Journal of Antimicrobial Chemotherapy, vol. 78, no. 4, 2023, pp. 1076-1083.
Vikelouda K, Simitsopoulou M, Antachopoulos C, et al. Pharmacodynamic and immunological interactions of amphotericin B formulations and voriconazole with human neutrophils against mature Scedosporium apiospermum and Fusarium spp. biofilms. J Antimicrob Chemother. 2023;78(4):1076-1083.
Vikelouda, K., Simitsopoulou, M., Antachopoulos, C., Skoura, L., & Roilides, E. (2023). Pharmacodynamic and immunological interactions of amphotericin B formulations and voriconazole with human neutrophils against mature Scedosporium apiospermum and Fusarium spp. biofilms. The Journal of Antimicrobial Chemotherapy, 78(4), 1076-1083. https://doi.org/10.1093/jac/dkad050
Vikelouda K, et al. Pharmacodynamic and Immunological Interactions of Amphotericin B Formulations and Voriconazole With Human Neutrophils Against Mature Scedosporium Apiospermum and Fusarium Spp. Biofilms. J Antimicrob Chemother. 2023 Apr 3;78(4):1076-1083. PubMed PMID: 36848199.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacodynamic and immunological interactions of amphotericin B formulations and voriconazole with human neutrophils against mature Scedosporium apiospermum and Fusarium spp. biofilms. AU - Vikelouda,Katerina, AU - Simitsopoulou,Maria, AU - Antachopoulos,Charalampos, AU - Skoura,Lemonia, AU - Roilides,Emmanuel, PY - 2022/09/28/received PY - 2023/02/09/accepted PY - 2023/4/4/medline PY - 2023/2/28/pubmed PY - 2023/2/27/entrez SP - 1076 EP - 1083 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 78 IS - 4 N2 - BACKGROUND: Mould infections caused by Scedosporium apiospermum and Fusarium solani species complex (FSSC) biofilms are rising among immunocompromised and immunocompetent patients. Little is known about the immunomodulatory effects of antifungal agents against these moulds. We examined the effects of deoxycholate and liposomal amphotericin B (DAmB, LAmB) and voriconazole on antifungal activities and immune responses of neutrophils (PMNs) against mature biofilms compared with their planktonic counterparts. METHODS: Antifungal activity of human PMNs exposed to mature biofilms and planktonic cells for 24 h was determined at effector-to-target ratios of 2:1 and 5:1, alone or combined with DAmB, LAmB and voriconazole, assessed as fungal damage by XTT assay. Cytokine production was evaluated by multiplex ELISA, following PMN stimulation with biofilms in the presence/absence of each drug. RESULTS: All drugs showed additive or synergistic effects with PMNs against S. apiospermum at 0.03-32 mg/L. They showed antagonism primarily against FSSC at 0.06-64 mg/L. Increased IL-8 was produced by PMNs exposed to S. apiospermum biofilms plus DAmB or voriconazole compared with PMNs exposed to biofilms alone (P < 0.01). During combined exposure, IL-1β was increased, an effect only counteracted by increased levels of IL-10 caused by DAmB (P < 0.01). LAmB and voriconazole caused similar IL-10 levels with those released by biofilm-exposed PMNs. CONCLUSIONS: The synergistic, additive or antagonistic effects of DAmB, LAmB or voriconazole on biofilm-exposed PMNs are organism-specific, with FSSC exhibiting greater resilience than S. apiospermum to antifungals. Biofilms of both moulds caused dampened immune responses. The drug-mediated immunomodulating effect on PMNs, evidenced by IL-1β, enhanced host protective functions. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/36848199/Pharmacodynamic_and_immunological_interactions_of_amphotericin_B_formulations_and_voriconazole_with_human_neutrophils_against_mature_Scedosporium_apiospermum_and_Fusarium_spp__biofilms_ DB - PRIME DP - Unbound Medicine ER -