Biomedical device associated infections are increasingly prevalent, and the incidence of fungal Candida associated infections has notably increased in recent history causing 45 % of hospital acquired infections in Australian Intensive Care Units. Prevention of this common fungal pathogen from adhering to these biomedical devices using antifungal surface coatings is paramount in minimising these events particularly in intensive care units and immunocompromised patients.
Using a novel antifungal coating, caspofungin covalently-tethered to medically-relevant biomaterials, we have demonstrated significant activity against pathogenic biofilm-producing Candida species including Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei which are contributing to polymicrobial implant infections. The surface activity of a tethered antibiotic may seem unconventional and therefore we have investigated alternative hypotheses for its activity, such as whether caspofungin is released from the surface. However, we present evidence from a mounting body of experimental data from surface chemical analysis and biological studies that strongly supports a contact-killing mechanism of action which likely involves the surface interaction and disruption of the fungal cell wall.
In order to transition the surface to in vivo testing we have undertaken intensive in vitro analysis including kinetic microscopy, biofilm quantitation through the static biofilm assay and investigated the sterilisation by autoclave and the storage conditions of the surface. The coating has also proven to be effective when coated on a variety of medically-relevant biomaterials including polypropylene, polycarbonate, polyethylene terephthalate (PET), polystyrene, and glass with activity against biofilm formation of five Candida species. These results successfully indicate that this coating has the potential to perform well in in vivo and clinical trials, and good potential for commercialisation.
We conclude that the caspofungin-attached polymer coatings are an effective deterrent in biofilm formation in vitro. Therefore, these surfaces show promise as a coating for minimising Candida spp. adhesion, colonisation and subsequent biofilm formation and infections on biomedical line devices and therefore warrants further investigation in vivo.