# Antimicrobial Synergy for Carbapenem-Resistant Enterobacteriaceae - Administrative Supplement

> **NIH NIH K08** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $27,878

## Abstract

Project Summary/Abstract – Parent K08
The proposed project is an investigation of the synergistic activity of antimicrobial combinations
against carbapenem-resistant Enterobacteriaceae (CRE). The principal investigator, Dr. Thea
Brennan-Krohn, recently completed fellowships in Pediatric Infectious Diseases and in Medical
Microbiology and is now an Instructor at Harvard Medical School and a post-doctoral fellow at
Beth Israel Deaconess Medical Center. She is interested in improving methods for detection and
characterization of antimicrobial synergy in order to guide the treatment of patients infected with
highly resistant pathogens. Her career goal is to become a leading investigator in the
development, implementation and interpretation of tests for detection of antimicrobial synergy.
During the award period, she will obtain a Master of Science in Pharmacology and will pursue
coursework in clinical and translational research. The proposed research will be carried out under
the mentorship of James Kirby, MD, D(ABMM), an NIH-funded investigator at Beth Israel
Deaconess Medical Center whose laboratory investigates topics highly relevant to the proposed
project, including the development of novel antimicrobial susceptibility testing methods and the
investigation of new therapeutics for CRE. Dr. Brennan-Krohn will be supported during the award
period by an advisory committee that includes Dr. George Eliopoulos, a world-renowned expert
on antimicrobial synergy. In the proposed project, Dr. Brennan-Krohn will initially test antimicrobial
combinations against a comprehensive collection of clinical CRE isolates in order to establish
combinatorial spectra of activity. For this part of the project, she will use an automated
checkerboard array microdilution method that makes use of the HP D300 inkjet printer-based
dispensing system. She will next develop a novel, fluorescent time-kill synergy assay in order to
investigate the bactericidal kinetics of synergistic combinations. Finally, she will investigate the in
vivo efficacy and PK/PD parameters of the most effective combinations using an
immunocompromised mouse model of CRE infection. Ultimately, the enhanced understanding of
synergy as well as the technology developed and validated during the proposed study are
expected to inform the design of prospective clinical trials of combination antibiotic therapy and
to establish simple, rapid synergy testing platforms that will for the first time provide synergy data
that can be used in a clinically actionable timeframe to guide patient care.

## Key facts

- **NIH application ID:** 10117330
- **Project number:** 3K08AI132716-03S1
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Thea Brennan-Krohn
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $27,878
- **Award type:** 3
- **Project period:** 2018-02-20 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117330

## Citation

> US National Institutes of Health, RePORTER application 10117330, Antimicrobial Synergy for Carbapenem-Resistant Enterobacteriaceae - Administrative Supplement (3K08AI132716-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10117330. Licensed CC0.

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