# The Role of Biofilm Formation in Antibiotic Tolerant Periprosthetic Joint Infection

> **NIH NIH R03** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $78,250

## Abstract

Abstract
 Total knee arthroplasty (TKA) is the largest major surgical procedure by volume for Medicare, and infection
is the largest reason for TKA revision. Irrigation and debridement (I&D) with long-term antibiotics is the preferred
method to manage periprosthetic joint infection (PJI; infected TKA). I&D fails in approximately 60% of cases.
The high failure rate of I&D is a result of the formation of biofilm on the implant and the subsequent high tolerance
of biofilm to antibiotics. There is a large gap in knowledge in how biofilm develops antibiotic tolerance, how it is
regulated, and there are no strategies to disrupt this tolerance in PJI. The hypothesis of this proposal is that
biofilm formation, regulated by toxin antitoxin systems, are a major factor responsible for the formation of
antibiotic tolerant biofilm. In other diseases of chronic infection (ie tuberculosis and cystic fibrosis), biofilm
formation and antibiotic tolerance have been well-recognized to decrease antibiotic efficacy. Understanding the
initial events that lead to the development of antibiotic tolerant biofilm in PJI is the first step in developing
treatment strategies. The aims include establishing the relationship between biofilm formation and antibiotic
tolerance. Preliminary results in this proposal demonstrate that biofilm formation is a critical step in the
development of antibiotic tolerant biofilm. In Aim 1, we have collected a library of PJI clinical isolates, and will
identify genetic and phenotypic differences in binding and antibiotic tolerant biofilm formation in these isolates.
In Aim 2, we will determine the role of toxin-antitoxin systems in PJI biofilm formation and association with
antibiotic tolerance in vitro and in the animal model we have developed. This will add further evidence to the role
of antibiotic tolerant biofilm in PJI to help direct improved the development of treatment strategies.

## Key facts

- **NIH application ID:** 10188719
- **Project number:** 1R03AR077602-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** KENNETH L URISH
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $78,250
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188719

## Citation

> US National Institutes of Health, RePORTER application 10188719, The Role of Biofilm Formation in Antibiotic Tolerant Periprosthetic Joint Infection (1R03AR077602-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10188719. Licensed CC0.

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