In Vitro Evaluation of Gentamicin or Vancomycin Containing Bone Graft Substitute in the Prevention of Orthopedic Implant-Related Infections

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.

Impact of Healthcare-Associated Infections Connected to Medical Devices—An Update

“…Various biodegradable carriers have been designed for antibiotics, such as CERA-MENT™, which is composed of 40% hydroxyapatite and 60% calcium sulfate. CERA-MENT™ is involved in the bone healing process in combination with vancomycin and gentamicin [144]. Gimeno et al (2018) demonstrated a high effectivity of cefazolin-loaded orthopedic implants [145].…”

Enhancement of Antibiofilm Activity of Ciprofloxacin against Staphylococcus aureus by Administration of Antimicrobial Peptides

“…The current study demonstrated that the AMPs melimine and Mel4 at sub-MICs did not induce resistance in S. aureus ATCC 25923. We and others [28][29][30][31] have tested several broad-spectrum antibiotics such as gentamicin (data not shown in the current study) and ciprofloxacin to determine whether strains such…”

“…The current study demonstrated that the AMPs melimine and Mel4 at sub-MICs did not induce resistance in S. aureus ATCC 25923. We and others [28][29][30][31] have tested several broad-spectrum antibiotics such as gentamicin (data not shown in the current study) and ciprofloxacin to determine whether strains such as S. aureus ATCC 6538, ATCC 25923, 31 and 38 can develop resistance to gentamycin and ciprofloxacin. Resistance to gentamicin or ciprofloxacin was not induced in any strain except S. aureus ATCC 25923 which developed resistance against ciprofloxacin.…”

Functionalization of Synthetic Bone Substitutes

“…The infection rates under use of bone substitute materials are reported to be up to 12% [ 3 ]. The bacterial spectrum in IRI consists with mainly staphylococci followed by streptococci, enterococci, Gram-negative rods and anaerobs [ 59 ]. This is in line with the findings in periprosthetic joint infection (PJI).…”