ANTIBIOTIC-LOADED HYDROGEL OUTPERFORMS CLINICAL GOLD STANDARD TREATMENT IN A LARGE ANIMAL MODEL OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IMPLANT-ASSOCIATED OSTEOMYELITIS

Boot W, Foster A, Schmid T, et al. ANTIBIOTIC-LOADED HYDROGEL OUTPERFORMS CLINICAL GOLD STANDARD TREATMENT IN A LARGE ANIMAL MODEL OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IMPLANT-ASSOCIATED OSTEOMYELITIS. Orthop Procs. 2019;101-B(SUPP_14):75-75. doi:10.1302/1358-992X.2019.14.075

Boot, W., et al. “ANTIBIOTIC-LOADED HYDROGEL OUTPERFORMS CLINICAL GOLD STANDARD TREATMENT IN A LARGE ANIMAL MODEL OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IMPLANT-ASSOCIATED OSTEOMYELITIS.” Orthopaedic Proceedings, vol. 101-B, no. SUPP_14, 2019, pp. 75-75., https://doi.org/10.1302/1358-992X.2019.14.075

Boot, W., Foster, A., Schmid, T., D'este, M., Zeiter, S., Eglin, D., Richards, G., & Moriarty, F. (2019). ANTIBIOTIC-LOADED HYDROGEL OUTPERFORMS CLINICAL GOLD STANDARD TREATMENT IN A LARGE ANIMAL MODEL OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IMPLANT-ASSOCIATED OSTEOMYELITIS. Orthopaedic Proceedings, 101-B(SUPP_14), 75-75. https://doi.org/10.1302/1358-992X.2019.14.075

Boot, W., Foster, A., Schmid, T., D'este, M., Zeiter, S., Eglin, D. et al. (2019) “ANTIBIOTIC-LOADED HYDROGEL OUTPERFORMS CLINICAL GOLD STANDARD TREATMENT IN A LARGE ANIMAL MODEL OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IMPLANT-ASSOCIATED OSTEOMYELITIS.” Orthopaedic Proceedings, 101-B(SUPP_14), pp. 75-75. Available at: https://doi.org/10.1302/1358-992X.2019.14.075

Boot, W., A. Foster, T. Schmid, M. D'este, S. Zeiter, D. Eglin, G. Richards, and F. Moriarty. “ANTIBIOTIC-LOADED HYDROGEL OUTPERFORMS CLINICAL GOLD STANDARD TREATMENT IN A LARGE ANIMAL MODEL OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IMPLANT-ASSOCIATED OSTEOMYELITIS.” Orthopaedic Proceedings 101-B, no. SUPP_14 (2019): 75-75. https://doi.org/10.1302/1358-992X.2019.14.075

Boot W, Foster A, Schmid T, D'este M, Zeiter S, Eglin D, et al. ANTIBIOTIC-LOADED HYDROGEL OUTPERFORMS CLINICAL GOLD STANDARD TREATMENT IN A LARGE ANIMAL MODEL OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IMPLANT-ASSOCIATED OSTEOMYELITIS. Orthop Procs. 2019 Dec 1;101-B(SUPP_14):75-75. https://doi.org/10.1302/1358-992X.2019.14.075

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Abstract

Aim

Implant-associated osteomyelitis is a devastating complication with poor outcomes following treatment, especially when caused by antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). A large animal model of a two-stage revision to treat MRSA implant-associated osteomyelitis has been developed to assess novel treatments. A bioresorbable, thermo-responsive hyaluronan hydrogel (THH) loaded with antibiotics has been developed and our aim was to investigate it´s in vivo efficacy as a local antibiotic carrier compared to the current standard of care i.e. antibiotic-loaded polymethylmethacrylate (PMMA) bone cement.

Method

12 female, 2 to 4 year old, Swiss Alpine Sheep were inoculated with MRSA at the time of intramedullary nail insertion in the tibia to develop chronic osteomyelitis. After 8 weeks sheep received a 2-stage revision protocol, with local and systemic antibiotics. Group 1 received the gold standard clinical treatment: systemic vancomycin (2 weeks) followed by rifampicin plus trimethoprim/sulfamethoxazole (4 weeks), and local gentamicin/vancomycin via PMMA. Group 2 received local gentamicin/vancomycin delivered via THH at both revision surgeries and identical systemic therapy to group 1. Sheep were euthanized 2 weeks following completion of antibiotic therapy. At euthanasia, soft tissue, bone, and sonicate fluid from the hardware was collected for quantitative bacteriology.

Results

Sheep tolerated the surgeries and both local and systemic antibiotics well. Gold standard of care successfully treated 3/6 sheep with a total of 10/30 culture-positive samples. All 6 sheep receiving antibiotic-loaded THH were successfully treated with 0/30 culture-positive samples, p=0.0008 gold-standard vs. hydrogel (Fisher's Exact).

Conclusions

The clinical gold standard treatment was successful in 50% of sheep, consistent with outcomes reported in the literature treating MRSA infection. The antibiotic-loaded THH clearly outperformed the gold standard in this model. Superior efficacy of the THH is likely due to 1) the ability to administer local antibiotics at the both revision surgies due to the bioresorbable nature of the hydrogel, and 2) complete antibiotic release compared to bone cement, which is known to retain antibiotics. Our results highlight the potential of local delivered, biodegradable systems for antibiotics for eradicating implant-related infection caused by antibiotic-resistant pathogens.