# The Gut Microbiome in Carbapenem-Resistant Enterobacteriaceae Colonization, Persistence, Infection, and Tolerance after Lung or Liver Transplantation

> **NIH NIH K23** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $179,145

## Abstract

PROJECT ABSTRACT
This resubmission is for a Mentored Patient-Oriented Research Career Development Award entitled “The Gut
Microbiome in Carbapenem Resistant Enterobacteriaceae (CRE) Colonization, Persistence, Infection, and
Tolerance after Lung or Liver Transplantation.” I am an Assistant Professor of Medicine and Transplant Infectious
Diseases physician at the University of Pittsburgh Medical Center (UPMC). I require additional training to develop
expertise as a translational researcher. My objective is to study the genetic characteristics of CRE that cause
gut colonization, persistence, and infection after lung/liver transplant, the phenomenon of tolerance in CRE, and
the gut microbiota environment associated with these events. My preliminary data suggest that (1) lung/liver
transplant recipients are at high risk for CRE colonization, with a subset developing persistent CRE colonization
and recurrent infections months to years after transplant, (2) last resort antibiotics like ceftazidime-avibactam
can induce tolerance in CRE in vitro, and (3) rectal CRE colonization after lung/liver transplant is associated with
marked dysbiosis and predominance of Proteobacteria. The scientific premise of this study is that long-term
CRE colonization after lung/liver transplant is a result of persistence of antibiotic-tolerant CRE isolates
that colonize the gut early after transplant, a process which is associated with a reduction in stool
diversity and abundance of Proteobacteria and maintained by ongoing dysbiosis. To test this central
hypothesis, I will be pursuing the following specific aims: (1a) to genetically characterize longitudinal CRE
isolates from these patients; (1b) to study antibiotic tolerance and resistance after exposure of these CRE to the
CRE-active antibiotics ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol,
and colistin; (1c) to identify risk factors for CRE colonization after lung/liver transplant; (2a) to determine whether
post-transplant stool microbiome profiles can predict future CRE colonization; and (2b and 2c) to define the stool
microbiota environment in which CRE colonization, persistence, and infection occur. This project will provide
novel insights into the genomic epidemiology and gut microbiome of lung/liver transplant recipients through the
entire spectrum of CRE colonization and disease. The proposed work will be conducted within the Division of
Infectious Diseases at UPMC and the Center for Medicine at the Microbiome at the University of Pittsburgh,
which have the computational and technical expertise required for bacterial genomic studies and microbial and
metagenomic sequencing. I am supported by committed mentors with complementary expertise in transplant
infectious diseases, Gram-negative resistance, microbiome research, and biostatistics. I will obtain a Certificate
in Clinical Research and receive didactic and hands-on training in microbiome and genomics research. Through
my training ...

## Key facts

- **NIH application ID:** 10357963
- **Project number:** 5K23AI154546-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Ghady Haidar
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $179,145
- **Award type:** 5
- **Project period:** 2021-02-22 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357963

## Citation

> US National Institutes of Health, RePORTER application 10357963, The Gut Microbiome in Carbapenem-Resistant Enterobacteriaceae Colonization, Persistence, Infection, and Tolerance after Lung or Liver Transplantation (5K23AI154546-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10357963. Licensed CC0.

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