Assessing the bioactive profile of anti-fungal loaded calcium sulfate against fungal biofilms

Butcher, M. C., Brown, J. L. , Hansom, D., Wilson-van Os, R., Delury, C., Laycock, P. A. and Ramage, G. (2021) Assessing the bioactive profile of anti-fungal loaded calcium sulfate against fungal biofilms. Antimicrobial Agents and Chemotherapy, 65(6), e02551-20. (doi: 10.1128/AAC.02551-20) (PMID:33753336)

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Abstract

Calcium sulfate (CS) has been used clinically as a bone or void filling biomaterial, and due to its resorptive properties have provided the prospect for its use as a release mechanism for local antibiotics to control biofilms. Here, we aimed to test CS beads loaded with three antifungal drugs against planktonic and sessile fungal species to assess whether these antifungal beads could be harnessed to provide consistent release of antifungals at biofilm inhibitive doses. A panel of different fungal species (n=15) were selected for planktonic broth microdilution testing with fluconazole (FLZ), amphotericin B (AMB) and caspofungin (CSP). After establishing planktonic inhibition, antifungal CS beads were introduced to fungal biofilms (n=5) to assess biofilm formation and cell viability through a combination of standard quantitative and qualitative biofilm assays. Inoculation of a hydrogel substrate, packed with antifungal CS beads, was also used to assess diffusion through a semi-dry material, to mimic active infection in-vivo. In general, antifungals released from CS loaded beads were all effective at inhibiting the pathogenic fungi over 7-days within standard MIC ranges for these fungi. We observed a significant reduction of pre-grown fungal biofilms across key fungal pathogens following treatment, with visually observable changes in cell morphology and biofilm coverage provided by scanning electron microscopy. Assessment of biofilm inhibition also revealed reductions in total and viable cells across all organisms tested. These data show that antifungal loaded CS beads produce a sustained antimicrobial effect, which inhibits and kills clinically relevant fungal species in-vitro as planktonic and biofilm cells.

Item Type:Articles
Additional Information:The authors would like to acknowledge funding support from Biocomposites for MB and GR.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Butcher, Mark and Hansom, Mr Donald and Brown, Dr Jason and Ramage, Professor Gordon
Authors: Butcher, M. C., Brown, J. L., Hansom, D., Wilson-van Os, R., Delury, C., Laycock, P. A., and Ramage, G.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:Antimicrobial Agents and Chemotherapy
Publisher:American Society for Microbiology
ISSN:0066-4804
ISSN (Online):1098-6596
Published Online:22 March 2021
Copyright Holders:Copyright © 2021 Butcher et al.
First Published:First published in Antimicrobial Agents and Chemotherapy 65(6): e02551-20
Publisher Policy:Reproduced under a Creative Commons license

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