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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.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 31 - 31
1 Dec 2016
Metsemakers W Schmid T Zeiter S Ernst M Keller I Cosmelli N Arens D Moriarty F Richards G
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Aim

The aim of this study was to define the role of implant material and surface topography on infection susceptibility in a preclinical in vivo model incorporating appropriate fracture biomechanics and bone healing.

Method

The implants included in this experimental study were composed of: standard Electro polished Stainless Steel (EPSS), standard titanium (Ti-S), roughened stainless steel (RSS) and surface polished titanium (Ti-P). In an in vivo study, a rabbit humeral fracture model was used. Each rabbit received one of three Staphylococcus aureus inocula, aimed at determining the infection rate at a low, medium and high dose of bacteria. Outcome measures were quantification of bacteria on the implant and in the surrounding tissues, and determination of the infectious dose 50 (ID50).


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 105 - 105
1 Dec 2015
Metsemakers W Emanuel N Cohen O Reichart M Schmid T Segal D Richards R Zaat S Moriarty T
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One of the most challenging complications in orthopedic trauma surgery is the development of infection. Improved infection prophylaxis could be achieved by providing local delivery of antibiotics directly to the tissue-implant interface. Especially implant-associated bone infections caused by antibiotic-resistant pathogens pose significant clinical challenges to treating physicians. Prophylactic strategies that act against resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), are urgently required.

The objective of this experimental study was to determine the efficacy of a biodegradable Polymer-Lipid Encapsulation MatriX (PLEX) loaded with the antibiotic doxycycline as a local prophylactic strategy against implant-associated osteomyelitis in a humeral non-fracture rabbit model.

Activity of the PLEX-doxycycline-coating was tested against both a doxycycline susceptible (doxyS) methicillin-susceptible S. aureus (MSSA) as well as a doxycycline-resistant (doxyR) MRSA. In a rabbit intramedullary (IM) nail-related infection model, twelve rabbits received an inoculum of a doxyS MSSA direct into the medullary cavity of the humerus. After inoculation, animals received either a PLEX-doxycycline-coated nail, or an uncoated nail. The animals were observed for four weeks. Upon euthanasia, quantitative bacteriology was performed to determine bacterial load in tissues and biofilm formation on the implant. A second study was performed with sixteen rabbits receiving a DoxyR MRSA inoculum, again in coated and uncoated groups.

In vitro elution studies revealed that 25% of the doxycycline was released from the PLEX-coated implants within the first day, followed by a 3% release per day up to day 28. Quantitative bacteriology revealed the presence of osteomyelitis in all animals receiving an uncoated nail in both the MSSA and the DoxyR MRSA studies (figure). All rabbits receiving a PLEX-doxycycline-coated nail were culture negative in the doxyS MSSA-group and the surrounding bone displayed a normal physiological appearance in both histological sections and radiographs. In the doxyR MRSA inoculated rabbits, a statistically significant reduction in the number of culture-positive samples was observed for the PLEX-doxycycline-coated group when compared to the animals that had received an uncoated nail, although the reduction in bacterial burden did not reach statistical significance.

Improved prophylaxis against infection in trauma and orthopedic implant surgery is clearly required today. In this study, we investigated a PLEX-doxycycline-coated IM nail in a humeral non-fracture rabbit model. The PLEX-doxycycline coating on titanium alloy implants provided complete protection against implant-associated MSSA osteomyelitis, and resulted in a significant reduction in the number of culture positive samples when challenged with a doxycycline-resistant MRSA.