Antibiotic loaded β-tricalcium phosphate/calcium sulfate for antimicrobial potency, prevention and killing efficacy of Pseudomonas aeruginosa and Staphylococcus aureus biofilms

Abstract

This study investigated the efficacy of a biphasic synthetic β-tricalcium phosphate/calcium sulfate (β-TCP/CS) bone graft substitute for compatibility with vancomycin (V) in combination with tobramycin (T) or gentamicin (G) evidenced by the duration of potency and the prevention and killing efficacies of P. aeruginosa (PAO1) and S. aureus (SAP231) biofilms in in vitro assays. Antibiotic loaded β-TCP/CS beads were compared with antibiotic loaded beads formed from a well characterized synthetic calcium sulfate (CS) bone void filler. β-TCP/CS antibiotic loaded showed antimicrobial potency against PAO1 in a repeated Kirby-Bauer like zone of inhibition assay for 6 days compared to 8 days for CS. However, both bead types showed potency against SAP231 for 40 days. Both formulations loaded with V + T completely prevented biofilm formation (CFU below detection limits) for the 3 days of the experiment with daily fresh inoculum challenges (P < 0.001). In addition, both antibiotic loaded materials and antibiotic combinations significantly reduced the bioburden of pre-grown biofilms by between 3 and 5 logs (P < 0.001) with V + G performing slightly better against PAO1 than V + T. Our data, combined with previous data on osteogenesis suggest that antibiotic loaded β-TCP/CS may have potential to stimulate osteogenesis through acting as a scaffold as well as simultaneously protecting against biofilm infection. Future in vivo experiments and clinical investigations are warranted to more comprehensively evaluate the use of β-TCP/CS in the management of orthopaedic infections.

In vitro elution characteristics of antibiotic‐loaded polymethylmethacrylate cement and a calcium sulfate bone substitute using staphylococci isolated from orthopedic implant‐associated infections

“…16,19 Similar to our results, recent studies have shown that the elution rates of antibiotics from calcium sulfate are successful at eradicating bacteria in surrounding tissues over time due to the initial high local antibiotic release, but this success occurs during a limited period of time due to the biodegradable properties of the antibiotics. 24,26 Nevertheless, many studies have only tested sensitive ATCC strains. 19 In addition to ATCC strains, we obtained more information by selecting well-investigated MDR staphylococcal clinical strains recovered from sonication fluid, and WGS analysis was performed to ensure that both strains exhibited resistance, MSCRAMMs (microbial surface components recognizing adhesive matrix molecules), and other biofilm-forming genes.…”

“…The antimicrobial elution method established for biofilm death (time kill curve) was based on that of Jiang et al 26 PMMA, PG-CSH and unloaded beads (5 beads per well) were placed in a 24-well tissue culture plate (Sarstedt, Newton, United States). Each well was inoculated with 2 mL of tryptone soya broth (TSB, Oxoid, Hampshire, United Kingdom) enriched with 1% glucose that contained 10 6 CFU/ mL of the bacterial strains (ATCC29213, ATCC12228, SA260, and SEPI216).…”

Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopedic Implant-Associated Infections In Vivo

“…A range of ceramic materials have been used in preclinical orthopedic antimicrobial applications including calcium sulfate, ,− hydroxyapatite, ,− β-tricalcium phosphate, zirconium nitride, borate bioactive glass, and calcium phosphate , (Table ). Several ceramics are intrinsically antimicrobial, such as calcium phosphate and bioactive glass; , however, for orthopedic implant infection applications, ceramics often incorporate antibiotics.…”

Antimicrobial potency, prevention ability, and killing efficacy of daptomycin-loaded versus vancomycin-loaded β-tricalcium phosphate/calcium sulfate for methicillin-resistant Staphylococcus aureus biofilms

“…Additionally, 10.3389/fmicb.2022.1029261 Frontiers in Microbiology 03 frontiersin.org β-TCP/CS has an osteoconductive effect and provides bone scaffolding (Urban et al, 2007;Fernandez de Grado et al, 2018;Zhao et al, 2020). Here, we analyzed the release characteristics of DAP and compared the efficiency of DAP with that of VAN in preventing and killing MRSA biofilms, concerning a previously established in vitro biofilm model (Jiang et al, 2021). Through these experiments, we provide a theoretical basis for the local administration of DAP for the treatment of IAIs in clinical settings.…”

“…The most challenging complications following joint replacement and fracture fixation procedures are implant-associated infections (IAIs), including periprosthetic joint infections (PJIs) and fracture-related infections (FRIs) ( Trampuz and Widmer, 2006 ; Horton et al, 2021 ). According to recent studies, the cumulative incidence after primary hip or knee arthroplasty is 0.5% in the first year and 1.4% within 10 years, whereas the incidence of FRI ranges from 0.4 to 16.1%, with an average of 5%, and up to 30% following open fractures ( Beam and Osmon, 2018 ; Foster et al, 2020 ; Jiang et al, 2021 ). Despite advances in surgical techniques, IAIs still pose great challenges to orthopedic surgeons, owing to their high risk of disability, mortality, and infection recurrence.…”