Pathological and microbiological impact of a gentamicin-loaded biocomposite following limited or extensive debridement in a porcine model of osteomyelitis

Abstract

Aims CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model. Methods Osteomyelitis was induced in nine pigs by inoculation of 104 colony-forming units (CFUs) of Staphylococcus aureus into a drill hole in the right tibia. After one week, the pigs were allocated into three groups. Group A (n = 3) received no treatment during the study period (19 days). Groups B (n = 3) and C (n = 3) received limited or extensive debridement seven days postinoculation, respectively, followed by injection of CERAMENT|G into the bone voids. The pigs were euthanized ten (Group C) and 12 (Group B) days after the intervention. Results All animals presented confirmatory signs of bone infection post-mortem. The estimated amount of inflammation was substantially greater in Groups A and B compared to Group C. In both Groups B and C, peptide nucleic acid fluorescence in situ hybridization (PNA FISH) of CERAMENT|G and surrounding bone tissue revealed bacteria embedded in an opaque matrix, i.e. within biofilm. In addition, in Group C, the maximal measured post-mortem gentamicin concentrations in CERAMENT|G and surrounding bone tissue samples were 16.6 μg/ml and 6.2 μg/ml, respectively. Conclusion The present study demonstrates that CERAMENT|G cannot be used as a standalone alternative to extensive debridement or be used without the addition of systemic antimicrobials. Cite this article: Bone Joint Res 2020;9(7):394–401.

Implant‐associated osteomyelitis: Development, characterisation, and application of a porcine model

“…Recent research has shown that the model can be used in studies involving a time frame of 19 days (Fig. 15) [12].…”

“…However, the extent to which locally applied antibiotics can penetrate into the surrounding bone tissue remains unclear. Recently, the porcine IAO model was use to investigate the microbiological impact of a gentamicin-loaded bone void filler, without simultaneous systemic antibiotic treatment, following limited or extensive debridement of osteomyelitis lesions [12]. Regardless of the type of debridement used, the bone void filler was contaminated with biofilm 10 days after revision surgery.…”

“…Regardless of the type of debridement used, the bone void filler was contaminated with biofilm 10 days after revision surgery. However, significantly less surrounding bone inflammation was present in cases of extensive debridement [12]. Consequently, the bone tissue concentrations of gentamicin obtained from the bone void filler may have been too low to eradicate the remnants of the mature biofilms left behind after debridement, allowing the carrier product to be colonized [12].…”

“…During the past 5 years, the porcine IAO model has been applied in several studies [10][11][12][13]. In brief, the model was used as the basis of an EU HORIZON 2020 Research and Innovation Programme project (Novel Marine Biomolecules Against Biofilm [NoMoRFilm] no.…”

“…An EU patent application based on the new coating technique is currently under review and describes very successful test results obtained using the porcine IAO model. In addition to the prophylactic coating studies, the porcine model was also recently used to evaluate the therapeutic impact of a gentamicin-loaded biodegradable bone void filler, following limited or extensive debridement of osteomyelitis lesions [12]. Currently, the porcine IAO model is also being used to investigate the molecular orchestration of bacterial bone infections.…”