# Adjuvant heat treatment for catheter salvage in central line associated bloodstream infection (HEATSAVE)

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $556,548

## Abstract

PROJECT SUMMARY:
Central line associated bloodstream infections (CLABSI), now considered a medical error, remain a significant
contributor to healthcare associated infections (HAIs) and associated morbidity and mortality. Despite ongoing
initiatives to adopt or adhere to specific recommendations and increased use of antibiotic impregnated
catheters, the incidence trend for CLABSIs has remained flat or increasing. The underlying pathophysiology is
related to biofilm formation on catheter surfaces which offer significant protection from host response and
antimicrobial therapy. Thus, definitive therapy often requires removal and replacement of catheters. However,
the patients at greatest risk for CLABSI (i.e., hemodialysis patients) also have high risk associated with
catheter replacement owing to: limited other vascular access points; life-sustaining nature of hemodialysis; and
significant co-morbidity increasing complication risk of instrumentation procedures. Our long-term goal is to
develop an effective catheter salvage strategy that removes biofilms from catheters in situ in patients whose
condition precludes device removal and replacement. We have found that modest elevations in temperature:
(1) soften biofilms, making them more likely to be mechanically dispersed; (2) reduce the total biomass from a
surface; and (3) augment antibiotic killing of constituent bacteria within a biofilm. Our preliminary data also
show that biomass dispersed by heat retains significant viability that can be completely mitigated by traditional
antibiotics. In a proof-of-principle experiment, we have shown that in-and-out cycling of a heated perfusate
reduces catheter-adhered biomass in a rat model of CLABSI. This work suggests that the application of heat
in conjunction with antibiotics is a promising catheter-salvage treatment strategy that could be quickly
translated to clinical practice. The objective of this study is to optimize the treatment parameters for the
application of heat and antibiotics for in situ CLABSI therapy in preparation for phase 1 human clinical trials.
We hypothesize that the addition of heat in combination with catheter lock and system antibiotics will reduce
bacterial load on the catheter and systemic dissemination. Our aims are to: (1) Determine the dose and
duration of heat therapy that maximizes biofilm dispersal and minimizes thermal injury; (2) Define a
generalizable description of the heat delivery required for biofilm eradication to allow translation from the rat to
the human setting; and (3) Determine the appropriate antibiotic regimen to be used in combination with the
heat therapy developed in Aim 1. Completion of these aims will provide a robust description of the heat flux
required to achieve biofilm eradication without thermal injury and the parameters required to administer that
treatment in a human dialysis catheter infection application. These parameters will form the basis for future
phase 1 clinical testing.

## Key facts

- **NIH application ID:** 10440832
- **Project number:** 1R01HL165464-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** J SCOTT VANEPPS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $556,548
- **Award type:** 1
- **Project period:** 2022-05-10 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440832

## Citation

> US National Institutes of Health, RePORTER application 10440832, Adjuvant heat treatment for catheter salvage in central line associated bloodstream infection (HEATSAVE) (1R01HL165464-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440832. Licensed CC0.

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