An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related Infection
Local antibiotic therapy is increasingly being recognised for its role in preventing and treating orthopaedic device-related infection (ODRI). A bioresorbable, injectable gentamicin-loaded hydrogel has been developed to deliver local antibiotics at the time of surgery with potential for both prevent...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-04-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.826392/full |
| _version_ | 1818478464523567104 |
|---|---|
| author | Willemijn Boot Andrew Lewis Foster Andrew Lewis Foster Andrew Lewis Foster Andrew Lewis Foster Olivier Guillaume David Eglin Tanja Schmid Matteo D’Este Stephan Zeiter Robert Geoff Richards Thomas Fintan Moriarty |
| author_facet | Willemijn Boot Andrew Lewis Foster Andrew Lewis Foster Andrew Lewis Foster Andrew Lewis Foster Olivier Guillaume David Eglin Tanja Schmid Matteo D’Este Stephan Zeiter Robert Geoff Richards Thomas Fintan Moriarty |
| author_sort | Willemijn Boot |
| collection | DOAJ |
| description | Local antibiotic therapy is increasingly being recognised for its role in preventing and treating orthopaedic device-related infection (ODRI). A bioresorbable, injectable gentamicin-loaded hydrogel has been developed to deliver local antibiotics at the time of surgery with potential for both prevention and treatment of ODRI. In a prophylaxis model, the antibiotic hydrogel was compared with systemic perioperative antibiotic prophylaxis alone in twelve sheep (six per group) at the time of intramedullary (IM) nail insertion to the tibia, which was inoculated with methicillin-sensitive Staphylococcus aureus (MSSA). In a treatment model of single-stage revision surgery, adjunctive antibiotic-loaded hydrogel was compared with systemic antibiotics alone in a single stage revision of MSSA infection associated with a tibia intramedullary nail in eleven sheep (five/six per group). The primary endpoint was quantitative microbiological results of soft tissue, bone and sonicate fluid from explanted hardware at the time of euthanasia. At euthanasia, the control sheep that received no local antibiotics in the prophylaxis model were all culture-positive (median 1x108, range 7x106-3x108 colony forming units, CFU) while only two of six sheep receiving local gentamicin had any culture positive biopsies (median 1x101, range 0 - 1x105 CFU). For the treatment model, sheep receiving only systemic antibiotics were all culture-positive (median 8x105, range 2x103- 9x106 CFU) while only two of six sheep treated with gentamicin-loaded hydrogel had any culture positive biopsies (median 3x102, range 0 - 7x104 CFU). Local gentamicin concentrations measured in extracellular fluid in the tibial canal show a burst release of gentamicin from the hydrogel. Serum gentamicin concentrations peaked in both models at one day post application and were below detection limit thereafter. This study has demonstrated the effective use of a locally delivered antibiotic hydrogel for both the prevention and treatment of ODRI that is superior to that of systemic antibiotics alone. Future studies will endeavour to translate from preclinical to clinical research trials. |
| first_indexed | 2024-12-10T09:48:39Z |
| format | Article |
| id | doaj.art-6b99d1394c644480b3c34aec08d0934f |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-10T09:48:39Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-6b99d1394c644480b3c34aec08d0934f2022-12-22T01:53:44ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-04-011210.3389/fcimb.2022.826392826392An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related InfectionWillemijn Boot0Andrew Lewis Foster1Andrew Lewis Foster2Andrew Lewis Foster3Andrew Lewis Foster4Olivier Guillaume5David Eglin6Tanja Schmid7Matteo D’Este8Stephan Zeiter9Robert Geoff Richards10Thomas Fintan Moriarty11AO Research Institute Davos, Davos, SwitzerlandAO Research Institute Davos, Davos, SwitzerlandQueensland University of Technology Centre for Biomedical Technologies, Brisbane, QLD, AustraliaJamieson Trauma Institute, Metro North Hospital and Health Service, Brisbane, QLD, AustraliaDepartment of Orthopaedic Surgery, Redcliffe Hospital, Queensland Health, Brisbane, QLD, AustraliaAO Research Institute Davos, Davos, SwitzerlandAO Research Institute Davos, Davos, SwitzerlandAO Research Institute Davos, Davos, SwitzerlandAO Research Institute Davos, Davos, SwitzerlandAO Research Institute Davos, Davos, SwitzerlandAO Research Institute Davos, Davos, SwitzerlandAO Research Institute Davos, Davos, SwitzerlandLocal antibiotic therapy is increasingly being recognised for its role in preventing and treating orthopaedic device-related infection (ODRI). A bioresorbable, injectable gentamicin-loaded hydrogel has been developed to deliver local antibiotics at the time of surgery with potential for both prevention and treatment of ODRI. In a prophylaxis model, the antibiotic hydrogel was compared with systemic perioperative antibiotic prophylaxis alone in twelve sheep (six per group) at the time of intramedullary (IM) nail insertion to the tibia, which was inoculated with methicillin-sensitive Staphylococcus aureus (MSSA). In a treatment model of single-stage revision surgery, adjunctive antibiotic-loaded hydrogel was compared with systemic antibiotics alone in a single stage revision of MSSA infection associated with a tibia intramedullary nail in eleven sheep (five/six per group). The primary endpoint was quantitative microbiological results of soft tissue, bone and sonicate fluid from explanted hardware at the time of euthanasia. At euthanasia, the control sheep that received no local antibiotics in the prophylaxis model were all culture-positive (median 1x108, range 7x106-3x108 colony forming units, CFU) while only two of six sheep receiving local gentamicin had any culture positive biopsies (median 1x101, range 0 - 1x105 CFU). For the treatment model, sheep receiving only systemic antibiotics were all culture-positive (median 8x105, range 2x103- 9x106 CFU) while only two of six sheep treated with gentamicin-loaded hydrogel had any culture positive biopsies (median 3x102, range 0 - 7x104 CFU). Local gentamicin concentrations measured in extracellular fluid in the tibial canal show a burst release of gentamicin from the hydrogel. Serum gentamicin concentrations peaked in both models at one day post application and were below detection limit thereafter. This study has demonstrated the effective use of a locally delivered antibiotic hydrogel for both the prevention and treatment of ODRI that is superior to that of systemic antibiotics alone. Future studies will endeavour to translate from preclinical to clinical research trials. https://www.frontiersin.org/articles/10.3389/fcimb.2022.826392/fullorthopaedic device related infectionlocal antibioticshydrogelfracture-related infectionperi-prosthetic joint infectionpreclinical |
| spellingShingle | Willemijn Boot Andrew Lewis Foster Andrew Lewis Foster Andrew Lewis Foster Andrew Lewis Foster Olivier Guillaume David Eglin Tanja Schmid Matteo D’Este Stephan Zeiter Robert Geoff Richards Thomas Fintan Moriarty An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related Infection Frontiers in Cellular and Infection Microbiology orthopaedic device related infection local antibiotics hydrogel fracture-related infection peri-prosthetic joint infection preclinical |
| title | An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related Infection |
| title_full | An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related Infection |
| title_fullStr | An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related Infection |
| title_full_unstemmed | An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related Infection |
| title_short | An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related Infection |
| title_sort | antibiotic loaded hydrogel demonstrates efficacy as prophylaxis and treatment in a large animal model of orthopaedic device related infection |
| topic | orthopaedic device related infection local antibiotics hydrogel fracture-related infection peri-prosthetic joint infection preclinical |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.826392/full |
| work_keys_str_mv | AT willemijnboot anantibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT andrewlewisfoster anantibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT andrewlewisfoster anantibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT andrewlewisfoster anantibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT andrewlewisfoster anantibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT olivierguillaume anantibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT davideglin anantibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT tanjaschmid anantibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT matteodeste anantibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT stephanzeiter anantibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT robertgeoffrichards anantibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT thomasfintanmoriarty anantibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT willemijnboot antibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT andrewlewisfoster antibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT andrewlewisfoster antibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT andrewlewisfoster antibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT andrewlewisfoster antibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT olivierguillaume antibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT davideglin antibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT tanjaschmid antibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT matteodeste antibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT stephanzeiter antibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT robertgeoffrichards antibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection AT thomasfintanmoriarty antibioticloadedhydrogeldemonstratesefficacyasprophylaxisandtreatmentinalargeanimalmodeloforthopaedicdevicerelatedinfection |