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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 18 - 18
10 Feb 2023
Foster A Boot W Stenger V D'Este M Jaiprakash A Crawford R Schuetz M Eglin D Zeiter S Richards R Moriarty T
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Local antimicrobial therapy is an integral aspect of treating orthopaedic device related infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability.

In this study, we compare the efficacy of PMMA versus an antibioticloaded hydrogel in a single- stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in

sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem.

There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture negative. Antibiotic delivery via hydrogel resulted in 10–100 times greater local concentrations for the first 2–3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits.

This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 75 - 75
1 Dec 2019
Boot W Foster A Schmid T D'este M Zeiter S Eglin D Richards G Moriarty F
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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.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 99 - 99
1 Dec 2017
Boot W D'Este M Schmid T Zeiter S Richards R Eglin D Moriarty T
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Aim

The treatment of chronic orthopedic device-related infection (ODRI) often requires multiple surgeries and prolonged antibiotic therapy. In a two-stage exchange procedure, the treatment protocol includes device removal and placement of an antibiotic-loaded bone cement spacer to achieve high local antibiotic concentrations. At the second stage, further surgery is required to remove the spacer and replace it with the definitive device. We have recently developed a thermo-responsive hyaluronan hydrogel (THH) that may be loaded with antibiotics and used as delivery system. Since the material is bio-resorbable, it does not require surgical removal and may therefore be suitable for use as treatment strategy in a single-stage exchange.

This aim of this study was to evaluate gentamicin sulphate (Genta)-loaded THH (THH-Genta) for treating a chronic Staphylococcus aureus ODRI in sheep using a single-stage procedure.

Methods

Twelve Swiss-alpine sheep received an IM tibia nail and an inoculation of a gentamicin-sensitive clinical strain of Staphylococcus aureus. After letting a chronic infection develop for 8 weeks, a revision procedure was performed: the implant was removed, the IM canal debrided and biopsies were taken for culture. The IM canal was then filled with 25ml THH-Genta (1% Genta) or left empty (control group) prior to the implantation of a sterile nail. An ultrafiltration probe was placed within the IM cavity to collect extracellular fluid and determine local antibiotic levels for 10 days. Both groups received systemic amoxicillin and clavulanic acid for 2 weeks, followed by 2 weeks without treatment for antibiotic washout. At euthanasia, IM nail, bone marrow, bone and tissue samples were harvested for quantitative bacteriology.