# Synovial Fluid and Joint Sepsis

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2021 · $440,970

## Abstract

ABSTRACT
In 2013, more than 20,000 patients in the US were diagnosed with joint infection. Despite surgical
intervention with debridement of necrotic tissue, aggressive lavage with antiseptic solutions, and systemic
antibiotic treatment, the mortality rate exceeds 11% and recurrence is common. Furthermore, the aggressive
treatments damage the joint ensuring later arthritis. Once bacteria access the joint capsule, our preliminary
data suggest that bacterial contaminants become recalcitrant to antibiotic treatments due to formation of large
bacterial aggregates that can be floating or loosely associated with tissues. We propose to develop new
treatments that disrupt and prevent re-formation of bacterial aggregates in septic joints to allow effective
antibacterial treatment. To attack this problem, we propose three specific aims: Specific Aim 1: To inhibit
bacterial aggregate formation in synovial fluid through treatment with drugs that alter protein aggregation. We
hypothesize that inhibition of aggregation will allow antibiotic access and increased effectiveness. Specific Aim
2: To permeabilize synovial fluid aggregates using ultrasound-mediated microbubble rupture in an ex vivo
model of the joint. We hypothesize that microbubble cavitation will permeabilize aggregates to increase
antibiotic efficacy towards bacteria within the clump. Specific Aim 3: To eradicate joint infection, in vivo,
through combined microbubble/drug/antibiotic treatments. We will test the hypothesis that joint infections
may be treated more effectively by the local application of microbubble cavitation in the presence of agents
from Specific Aim 1 and amikacin. To attack this problem, we have assembled a team of experts in orthopaedic
infection, animal models of disease, ultrasound physics, musculoskeletal disease together with a practicing
orthopaedic surgeon specializing in joint infection. The success of our proposed approach will lead to higher
treatment success rates, so that the pain, cost, suffering and mortality associated with joint infections will be
markedly reduced.

## Key facts

- **NIH application ID:** 10183167
- **Project number:** 5R01AR072513-05
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Noreen J Hickok
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $440,970
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183167

## Citation

> US National Institutes of Health, RePORTER application 10183167, Synovial Fluid and Joint Sepsis (5R01AR072513-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10183167. Licensed CC0.

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