# Diagnosis and Tracking of Spinal Staphylococcus aureus Orthopaedic Implant Infections

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2022 · $207,142

## Abstract

Spinal infections are a serious complication of vertebral implantation surgery with a death rate as high as 20%
in the first year. Challenging to identify, especially in the early stages, they are typically diagnosed after
becoming well established when the patient is experiencing significant pain and permanent vertebral damage.
Here, we propose to explore the early immune response to these infections, focusing on Staphylococcus
aureus, (S. aureus), the most frequent and serious among the multiple pathogens that cause spinal implant
infections. Our goal is to develop a new way to diagnose spinal implant infections that will: 1) be usable early in
the infection's course, 2) cost less than current approaches, 3) require only a routine blood sample, and 4) be
capable of monitoring therapeutic success. Most patients have high circulating levels of S. aureus-specific
antibodies, and these levels increase with infection, but remain elevated long after the infection has been
resolved. To provide a more sensitive diagnostic tool and at the same time create a simple measure for
monitoring therapeutic success, we propose to measure the antibodies produced by circulating Antibody-
Secreting Cells (ASC) that are present in the blood while the infection is ongoing and rapidly decline thereafter.
ASC can be harvested from whole blood, washed free of serum antibodies, and cultured in vitro for a short
time. These cultured cells will secrete newly synthesized antibodies, as well as the cytokines, yielding “medium
enriched for newly synthesized antibodies” or MENSA, for short. Antibody titers of MENSA fluid against
antigens for specific pathogens and the cytokines being secreted can be measured using a multiplex
immunoassay. In this proposal, we hypothesize that the diagnosis and monitoring of treatment response due to
spine related S. aureus infection is feasible utilizing pathogen-specific antibodies secreted by ASC, and that
the antigenic signatures will be distinct compared to other musculoskeletal infections. To test this hypothesis,
we will examine MENSA antibody and cytokine levels in patients with a known or suspected infection
associated with previously placed spinal orthopedic implants. We will determine if MENSA antibodies alone or
in combination with cytokines can discriminate between patients with S. aureus infections or infections due to
other pathogens. Accuracy will be determined by comparing to the clinical gold standard of bacterial culture.
We will also determine if we can use MENSA to track the response to treatment for S. aureus infection. This
study is focused on S. aureus as we can diagnosis this pathogen via culture, giving us a benchmark for
accuracy, even though 48% of the time, the infectious agent in spine infections cannot be determined by
culture. This study is a proof-of-concept study that can be expanded to other pathogens that are complex to
diagnose while also monitoring treatment when direct culture methods become impractical. T...

## Key facts

- **NIH application ID:** 10464246
- **Project number:** 1R21AI169736-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Cheryl Lynne Ackert-Bicknell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $207,142
- **Award type:** 1
- **Project period:** 2022-01-24 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464246

## Citation

> US National Institutes of Health, RePORTER application 10464246, Diagnosis and Tracking of Spinal Staphylococcus aureus Orthopaedic Implant Infections (1R21AI169736-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10464246. Licensed CC0.

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