# Impact of early gut microbiome features on risk of neutropenic fever and bloodstream infection in hematologic malignancy

> **NIH NIH K23** · UNIVERSITY OF PENNSYLVANIA · 2021 · $194,940

## Abstract

PROJECT SUMMARY/ ABSTRACT
Both neutropenic (NTP) fever and bloodstream infections (BSIs) are common complications in patients
receiving treatment for hematologic malignancy and are associated with increased length of stay, cost of care,
and mortality. Chemotherapy and neutropenia result in the disruption of the gastrointestinal mucosa, leading to
translocation of commensal bacteria from the gut, causing NTP fever, and in some cases BSI. The study of the
impact of the gut microbiome is critical to understanding the pathogenesis of, and risk for, NTP fever. To
prevent BSIs and treat NTP fever, patients are exposed to both prophylactic and empiric broad-spectrum
antibiotics. However, the decision for antibiotic prophylaxis and the choice of therapy with empiric antibiotics
are typically based on provider preference. This is due to a lack of data to inform antibiotic treatment and
selection of specific agents for individual patients. Utilizing the gut microbiome to predict NTP fever and BSI
may allow for personalized antibiotic decisions, to determine which patients will benefit most from antibiotic
prophylaxis while limiting excess antibiotic exposures in those at low risk of NTP fever and BSI.
 The candidate plans to study the ability of the early gut microbiome before and change after
chemotherapy to predict NTP fever (Aim 1.1). This includes an investigation of the impact of the gut
microbiome on measures of gut mucosal integrity and microbe-induced inflammation. This proposal also aims
to discriminate microbiome features of patients with NTP fever who ultimately develop BSI from those patients
who do not (Aim 1.2). This will be accomplished through longitudinal collection of patient samples, focusing on
a broad patient population at risk of these events, specifically patients admitted for chemotherapy and stem cell
transplantation for treatment of hematologic malignancy. In addition, the candidate will investigate the impact of
specific antibiotic exposures on the gut microbiome over the course of admission to understand how specific
antibiotic choices, including prophylaxis, impact the gut microbiome (Aim 2).
 The results of this study may allow future clinicians to utilize early gut microbiome features in patients
receiving treatment for hematologic malignancy to predict NTP fever and BSI. This knowledge will help inform
the decision for antibiotic prophylaxis using individual patient factors and will help guide selection of specific
antibiotics used for the treatment of NTP fever that also reduce the risk of microbiome disruption. The aims are
combined with a robust training plan that includes formal training and education in bioinformatics, molecular
epidemiology, and biostatistics, the development of advanced analytic skills for microbiome data, formal
benchmarks for progress including presentation at seminars and international conferences, and extensive
research experience under the guidance of an expert mentoring and advisory team. This p...

## Key facts

- **NIH application ID:** 10104435
- **Project number:** 5K23AI143925-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Matthew Ziegler
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $194,940
- **Award type:** 5
- **Project period:** 2020-02-13 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104435

## Citation

> US National Institutes of Health, RePORTER application 10104435, Impact of early gut microbiome features on risk of neutropenic fever and bloodstream infection in hematologic malignancy (5K23AI143925-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10104435. Licensed CC0.

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