Clinical trial NCT04897971: Serum Based Diagnosis of and Monitoring of Infection Recovery in Orthopedic Spine Implant Infections
Official title: Use of MENSA to Improve the Diagnosis of Causative Infectious Agent and Monitor Infection Recovery in Orthopedic Spine Infection
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Staphylococcus Aureus Infection
Surgical Site Infection
Orthopedic Procedures
Spine
Keywords: Spine, Orthopedic Implant infection
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: University of Rochester
First posted: 2021-05-24
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients undergoing revision spine surgeries at the University of Colorado Hospital. with suspected infection of previous instrumentation will be offered enrollment. The enrolled patients will be identified prior to surgery by the surgeons and research staff through radiographs and images contained in the medical records and the parameters of suspected infection which include:

* Blood biomarkers: elevated C-reactive protein (CRP) and ESR (erythrocyte sedimentation rate), and white blood cell count
* X-ray imaging: to show osteolysis and possibly implant-loosening
* MRI or CT imaging: looking for fluid accumulations, evidence of inflammation, enhancements.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The percentage of Staphylococcus aureus spine implant associated infections correctly identified by "medium enriched for newly synthesized antibodies" (MENSA)
timeFrame: Baseline
measure: Change "Medium enriched for newly synthesized antibodies" (MENSA) titers in the post-operative period
timeFrame: 2 weeks, 6 weeks, 3 months, 6 months, 1 year and 2 years post-surgery
measure: "Medium enriched for newly synthesized antibodies" (MENSA) titers in spine implant infections compared to S. aureus infections of other orthopedic site infections.
timeFrame: Baseline
Secondary outcomes:
measure: Confirmation of Staphylococcus aureus in spine implant associated infection by polymerase chain reaction (PCR)
timeFrame: Baseline
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Univeristy of Colorado Denver
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Cheryl L Ackert-Bicknell, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.