The mechanisms of action of commercial antimicrobial agents are generally well-understood from classical pharmacokinetic studies in solution. However, using surface coatings to deliver antimicrobials might be an innovative way to prevent microbial colonisation of hospital surfaces or on implantable medical devices. Furthermore, we provide evidence that they may work by novel mechanisms.
Fungal pathogens tend to be overlooked as causative agents in severe patient infections, yet they importantly contribute to clinically-challenging polymicrobial biofilms on medical devices and are becoming increasingly implicated in hospital outbreaks related to external materials. Since approved antifungal agents are scarce, and only a handful in development, new uses for existing drugs such as reformulation in surface coatings is an idea worth exploring.
We have produced antifungal materials incorporating three classes of antifungals: triazoles, polyenes, and echinocandins and evaluated these in vitro. Since each of these classes has a different drug target, we aim to understand how fungal cells interface with materials. To reach intracellular targets, fluconazole-eluting coatings were appropriate and effective. To interact with membrane-associated ergosterol, polyenes also required elution, because we found that surface attachment eliminated activity. The echinocandins are an interesting case. We found that covalent attachment of caspofungin, micafungin, and anidulafungin resulted in highly effective antifungal coatings which eliminated yeasts on contact and have evidence to show that this was not a result of elution from the surface. The surface remained effective (> 106 yeast killing) even after being challenged 5 times with fresh inoculum. While the biophysics of how immobilised echinocandins interact with the β-1,3-glucan synthase complex is an ongoing investigation, our data suggest a mechanism that does not rely on free diffusion. This raises interesting questions about how fungal cells interface with surfaces, the dynamic nature of the fungal cell wall, and the accessibility of cell wall drug targets. With this new knowledge, we see good potential to develop novel materials that combat microbial biofilms.