# Regional genomic epidemiology to identify drivers of resistance, transmission and infection with carbapenem-resistant Klebsiella pneumoniae

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $449,257

## Abstract

The emergence and worldwide dissemination of antibiotic resistant organisms represents a significant
threat to global public health. An organism that epitomizes both the urgency and challenges associated with
this threat is carbapenem-resistant Klebsiella pneumoniae (CRKP). CRKP was first observed in a clinical case
in 1996 in a hospital in North Carolina. Since that time, successful lineages of CRKP have spread across the
globe, becoming endemic in healthcare networks in many regions. This increasing prevalence of CRKP poses
a great risk to hospitalized patients, as crude mortality rates for CRKP infections can be upwards of 50%.
Moreover, the threat associated with CRKP continues to escalate, with numerous reports of CRKP that are
resistant to even last-line antibiotics, leaving affected patients with limited treatment options. The seriousness
of the CRKP epidemic has led to both the U.S. Centers for Disease Control and the World Health Organization
ranking it as their most urgent antibiotic resistant threat. However, despite the attention given to CRKP, it
remains highly prevalent in many areas. Our central hypothesis is that our inability to effectively control CRKP,
as well as other urgent antibiotic resistant threats, is due to a lack of understanding of the clinical and
epidemiologic factors that drive the emergence and spread of antibiotic resistant organisms across regional
healthcare networks. Here, we seek to overcome this knowledge gap by first applying whole-genome
sequencing to construct regional transmission networks for CRKP, and then overlaying rich epidemiologic and
clinical meta-data to identify drivers of transmission, resistance evolution and infection across regional
healthcare facilities. These goals will be accomplished through the following three aims: 1) apply phylogenetic
methods to reconstruct regional transmission networks, and perform data analysis and modeling to identify
drivers of transmission within and between hospitals, 2) identify genetic determinants of resistance to last line
antibiotics and analyze in the context of the regional transmission network and clinical metadata to identify
factors associated with both the evolution and acquisition of resistance and 3) identify genetic determinants
associated with CRKP infection and analyze in the context of the regional transmission networks and patient
meta-data to identify virulent sub-lineages and convergent variation that are associated with poor patient
outcomes. The totality of these aims will provide critical insight into the factors driving transmission, resistance
evolution and infection with CRKP as it spreads across regional healthcare networks. Moreover, we believe our
approach of integrating genomic, clinical and epidemiologic data to study the proliferation of antibiotic resistant
threats at a regional level can be applied in other contexts to help guide regional infection prevention.

## Key facts

- **NIH application ID:** 10241899
- **Project number:** 5R01AI148259-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Evan Snitkin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $449,257
- **Award type:** 5
- **Project period:** 2020-08-19 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241899

## Citation

> US National Institutes of Health, RePORTER application 10241899, Regional genomic epidemiology to identify drivers of resistance, transmission and infection with carbapenem-resistant Klebsiella pneumoniae (5R01AI148259-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10241899. Licensed CC0.

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