Bioactive glass S53P4 cream kills ESKAPE panel multidrug resistant pathogens and Staphylococcus aureus biofilms

IntroductionOrthopedic implant-associated infections, predominantly caused by S. aureus, pose significant challenges due to biofilm formation and antibiotic resistance. Bioactive Glass (BAG) S53P4 is a unique material with antimicrobial and bone regenerative properties. We aimed to characterize a novel BAG S53P4 cream, consisting of BAG powder and a binder, for its capacity to kill Staphylococcus aureus in suspension and biofilms in the absence or presence of titanium implant material. Since the BAG antimicrobial activity depends on ions eluted, we also analyzed the eluates of the cream and of powder and binder.MethodsBAG cream, BAG powder, and binder were evaluated for antimicrobial activity against planktonic S. aureus in the presence or absence of titanium implant material, and against S. aureus biofilms. Eluates collected at different time points were tested against a panel of bacterial and fungal pathogens. Elemental ion release and pH changes were measured over time. Time-kill and biofilm assays were performed. Additionally, the applicability and antimicrobial efficacy of BAG cream were evaluated in a cadaver mouse bone defect model.ResultsThe BAG cream and BAG powder applied to titanium implant material, as well as their respective eluates eradicated planktonic S. aureus. Elemental release from BAG cream and powder showed time-dependent shifts in levels of silicon, sodium, calcium and phosphorous together with stable alkaline pH levels, reflecting continuous ion release from the glass network and concurrent precipitation of calcium phosphate and silica phases. BAG cream and powder eluates collected as early as at 2 h were highly effective against S. aureus, the ESKAPE panel of multidrug resistant pathogens, colistin-resistant Escherichia coli and Cutibacterium acnes, and against the fungi Candidozyma auris and Candida albicans. The eluates displayed time-dependent bactericidal activity with significant bacterial killing starting already at 30 min and increasing with longer exposure times. Moreover, significant reduction in S. aureus biofilm was observed with the cream and powder eluates. BAG cream was easy to apply to the bone defect of a cadaver mouse using a syringe and it effectively prevented S. aureus growth.ConclusionThese findings show the potential of BAG cream as an innovative application form of BAG S53P4 offering a promising approach against orthopedic implant-associated infections.