Serum Based Diagnosis of and Monitoring of Infection Recovery in Orthopedic Spine Implant Infections

Overview

The goal of this study is to test a new way to diagnose and track treatment of spine infections caused by the bacteria Staphylococcus aureus.

Full Title of Study: “Use of MENSA to Improve the Diagnosis of Causative Infectious Agent and Monitor Infection Recovery in Orthopedic Spine Infection”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: May 2026

Detailed Description

Ongoing Staphylococcus aureus (S. aureus) infections of the spine associated with orthopedic hardware implants elicit prominent immune responses against a repertoire of proteins characteristic of the invading pathogen. Antibodies specific for these antigens can be measured in the serum or in a novel sample created by culturing circulating Antibody Secreting Cells (ASC) in vitro where they create an analytic fluid called here "medium enriched for newly synthesized antibodies" (MENSA). The hypothesis of this study addresses three essential attributes of this analytic approach that can yield both a valuable tool for research on spinal infections and in the future, this can be developed a clinical tool for diagnosis and monitoring of therapeutic success in patients. By measuring the emergence of these signature antibodies in the serum and/or MENSA, the goals of this study are: 1) To differentiate between patients with an ongoing S. aureus infections, not just "general infection, in the spine using only blood samples; 2) To track the success (or failure) of therapeutic interventions; and 3) to distinguish spinal infections from S. aureus infections in other sites by the repertoire of antibodies that are elicited.

Interventions

  • Diagnostic Test: Medium enriched for newly synthesized antibodies in spine infection
    • Medium enriched for newly synthesized antibodies titers in patients with Staphylococcus aureus infections of orthopedic spine implants at baseline and in the post operative period

Arms, Groups and Cohorts

  • Spine implant associated infection cohort
    • Adult patients undergoing revision spine surgeries with suspected infection of previous instrumentation.

Clinical Trial Outcome Measures

Primary Measures

  • The percentage of Staphylococcus aureus spine implant associated infections correctly identified by “medium enriched for newly synthesized antibodies” (MENSA)
    • Time Frame: Baseline
    • “A medium enriched for newly synthesized antibodies” (MENSA) is the supernatant collected from cultured antibody secreting cells. Peripheral blood monocytes (PBMCs) are washed and placed into cell culture. After 24 hours, the media contains a high concentration of newly made antibodies. This media is referred to as MENSA. This is tested to see if the antibodies collected react against a panel of antigens. MENSA immunoglobulin G (IgG) titers for each antigen will be assessed for their predictive ability to identify the presence of S. aureus in spine implant-associated infections using receiver operating characteristic (ROC) curve analysis (alone or in combination), with overall prediction accuracy summarized by the area-under-the-curve (AUC). Participants will then be categorized as Staphylococcus aureus (S. aureus) positive or negative based on MENSA. The percentage of correctly identified S. aureus determinations compared to clinical diagnosis will be determined.
  • Change “Medium enriched for newly synthesized antibodies” (MENSA) titers in the post-operative period
    • Time Frame: 2 weeks, 6 weeks, 3 months, 6 months, 1 year and 2 years post-surgery
    • MENSA IgG titers (as defined in Outcome 1) will be measured at 2 weeks, 6 weeks, 3 months, 6 months, 1 year and 2 years post-surgery. A longitudinal measure of antibody activity defined as the average change per study visit from baseline will used to track infection clearance versus persistent infection. Levels of anti-S. aureus antibodies in MENSA should decline to background in patients whose infections have been successfully treated and remain elevated in those whose infections persist.
  • “Medium enriched for newly synthesized antibodies” (MENSA) titers in spine implant infections compared to S. aureus infections of other orthopedic site infections.
    • Time Frame: Baseline
    • MENSA IgG titers (as defined in Outcome 1) will be compared to responses measured in a pre-existing collection of samples from patients who had experienced: 1) prosthetic joint infections; 2) septic arthritis; 3) diabetic foot infections; 4) soft-tissue infections; and 5) fracture-related infections. The goal will be to identify a combination of antigens that is uniquely discriminatory for spine infections.

Secondary Measures

  • Confirmation of Staphylococcus aureus in spine implant associated infection by polymerase chain reaction (PCR)
    • Time Frame: Baseline
    • Total DNA will be collected from surgical discarded tissue from sites adjacent to the infection. polymerase chain reaction (PCR) using primers that amplify a region of the Staphylococcus aureus genome will be run to confirm the presence/absence of Staphylococcus aureus at the infection site.

Participating in This Clinical Trial

Inclusion Criteria

  • patients with known or suspected spinal infections associated with spinal orthopedic implant(s); – patients over 18 years of age and younger than 85; – patients undergoing spinal revision surgery. Exclusion Criteria:

  • Diagnosed as immuno-compromised or immuno-suppressed based on medication use; – On-going or previously diagnosed musculoskeletal infections associated non-spine hardware (e.g., prosthetic hip, prosthetic knee, prosthetic shoulder); – Current diabetic foot ulcer/infection; – Patients undergoing cancer treatment (including radiation and chemotherapies); – Pregnancy; – Absence of a spleen; – Over the age of 85 or under the age of 18. – Weigh less than 110 pounds, or for which it would otherwise be unsafe for them to undergo a blood draw.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Colorado, Denver
  • Collaborator
    • University of Rochester
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Cheryl L Ackert-Bicknell, PhD, Principal Investigator, University of Colorado, Denver

References

Muthukrishnan G, Soin S, Beck CA, Grier A, Brodell JD Jr, Lee CC, Ackert-Bicknell CL, Lee FE, Schwarz EM, Daiss JL. A Bioinformatic Approach to Utilize a Patient's Antibody-Secreting Cells against Staphylococcus aureus to Detect Challenging Musculoskeletal Infections. Immunohorizons. 2020 Jun 22;4(6):339-351. doi: 10.4049/immunohorizons.2000024.

Oh I, Muthukrishnan G, Ninomiya MJ, Brodell JD Jr, Smith BL, Lee CC, Gill SR, Beck CA, Schwarz EM, Daiss JL. Tracking Anti-Staphylococcus aureus Antibodies Produced In Vivo and Ex Vivo during Foot Salvage Therapy for Diabetic Foot Infections Reveals Prognostic Insights and Evidence of Diversified Humoral Immunity. Infect Immun. 2018 Nov 20;86(12):e00629-18. doi: 10.1128/IAI.00629-18. Print 2018 Dec.

Nishitani K, Beck CA, Rosenberg AF, Kates SL, Schwarz EM, Daiss JL. A Diagnostic Serum Antibody Test for Patients With Staphylococcus aureus Osteomyelitis. Clin Orthop Relat Res. 2015 Sep;473(9):2735-49. doi: 10.1007/s11999-015-4354-2. Epub 2015 May 27.

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