Biomarkers in prosthetic joint infection & the molecular role of antibiotics in soft tissue repair

Atherton, Caroline Margaret (2021) Biomarkers in prosthetic joint infection & the molecular role of antibiotics in soft tissue repair. MD thesis, University of Glasgow.

Abstract

Background: In Orthopaedic surgery the diagnosis, treatment and prevention of infection are key to successful patient outcomes, this has led to the increased use of antibiotics. Infection following implant or graft surgery has high levels of patient morbidity and associated costs of treatment. Antibiotic prophylaxis coupled with early accurate diagnosis can improve outcomes. Currently, implant related infection is diagnosed using diagnostic algorithms which combine numerous blood and tissue investigations, however, there is no single test available to rule infection in or out and reliance on clinical judgement is still at the forefront. Novel gene sequencing techniques are coming to the forefront of diagnostics across all medical specialties and here I present a pilot study of the use of a new sequencing method and diagnostic rationale - looking at the patient’s own immune response to identify the presence of implant infection. Antibiotic prophylaxis, usually given intravenously at the time of surgery has led to a significant reduction in implant infection. Developing more localised ways to administer this prophylaxis led to the introduction of an antibiotic ‘wrap’ - whereby tissue graft is wrapped in antibiotic solution prior to insertion. This method has significantly reduced infection rates following graft surgery however, it remains unknown if this antibiotic has any adverse molecular or biomechanical effect on the graft tissue, an issue this work aims to address.

Key Findings: Tissue and blood from patients undergoing orthopaedic implant related revision surgery was sequenced on a novel immune gene panel. From this, patterns of gene expression were identified in tissue which defined the infected from the aseptic control cohort. Furthermore, the immune gene response was able to characterise different time points of infection, identifying signatures for acute infection and chronic infection. Sequencing blood samples from the same cohort I was able to establish a gene signature which provided genus level bacterial identification, previously only provided following microbiology culture. Vancomycin antibiotic treatment of tendon graft tissue, used in anterior cruciate ligament reconstruction, was not associated with an increase in apoptotic gene or protein expression. Furthermore, no consistent changes were seen in tendon matrix gene or protein expression. I did identify a consistent trend of reduced levels of inflammatory cytokines following vancomycin compared with control conditions.

Conclusions: Novel gene sequencing techniques and a ‘switched’ diagnostic strategy have shown promise in diagnosing and categorising infection in orthopaedic implant surgery. Antibiotic ‘wrap’ of the hamstring graft in ACL surgery may induce a beneficial homeostatic molecular environment, via a reduction in inflammatory cytokines.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Subjects: Q Science > QR Microbiology > QR180 Immunology; R Medicine > R Medicine (General); R Medicine > RD Surgery
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Supervisor's Name: McInnes, Professor Iain B. and Millar, Professor Neal
• Date of Award: 2021
• Depositing User: Theses Team
• Unique ID: glathesis:2021-82563
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 11 Nov 2021 10:40
• Last Modified: 14 Nov 2022 16:17
• Thesis DOI: 10.5525/gla.thesis.82563
• URI: https://theses.gla.ac.uk/id/eprint/82563