Abstract

Antibiotic-loaded bone graft substitutes are attractive clinical options and have been used for years either for prophylaxis or therapy for periprosthetic and fracture-related infections. Calcium sulfate and hydroxyapatite can be combined in an injectable and moldable bone graft substitute that provides dead space management with local release of high concentrations of antibiotics in a one-stage approach. With the aim to test preventive strategies against bone infections, a commercial hydroxyapatite/calcium sulfate bone graft substitute containing either gentamicin or vancomycin was tested against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, harboring different resistance determinants. The prevention of bacterial colonization and biofilm development by selected microorganisms was investigated along with the capability of the eluted antibiotics to select for antibiotic resistance. The addition of antibiotics drastically affected the ability of the selected strains to adhere to the tested compound. Furthermore, both the antibiotics eluted by the bone graft substitutes were able to negatively impair the biofilm maturation of all the staphylococcal strains. As expected, P. aeruginosa was significantly affected only by the gentamicin containing bone graft substitutes. Finally, the prolonged exposure to antibiotic-containing sulfate/hydroxyapatite discs did not lead to any stable or transient adaptations in either of the tested bacterial strains. No signs of the development of antibiotic resistance were found, which confirms the safety of this strategy for the prevention of infection in orthopedic surgery.

Highlights

  • In the 1960s, the first total knee and hip replacements were implanted in patients, heralding the starting point of a revolution in orthopedic surgery [1]

  • Different from SauS, the glycopeptide-intermediate S. aureus (GISA) strain showed no significant difference in the adhesion to sandblasted titanium (ST) or ceramic bone void filler (CBVF)

  • containing gentamicin (CG) and CV were still able to prevent the adhesion of GISA at all time points completely (0 colony forming units (CFU)/mL)

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Summary

Introduction

In the 1960s, the first total knee and hip replacements were implanted in patients, heralding the starting point of a revolution in orthopedic surgery [1]. IRI may be divided into periprosthetic joint infections (PJI) [2,3,4] and fracture-related infections (FRI) [5,6], both presenting two different clinical and surgical challenges. An immature biofilm continues growing in cellular density and, later on, extracellular components promote microbial aggregation and stimulate the development of the slimy extracellular matrix, conferring extreme resistance to the action of immune cells and antimicrobials [9]. The additional use of local antibiotics can achieve high doses of active drugs exceeding the minimum inhibitory concentrations (MICs) [11] exclusively at the site of infection, thereby optimizing therapeutic efficacy and minimizing the risk of systemic toxicity [14]

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