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Decoding multidrug-resistant pathogen dynamics for clinically-relevant wastewater surveillance

Award Number: DP2AI192737
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/23/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2030

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Decoding multidrug-resistant pathogen dynamics for clinically-relevant wastewater surveillance - Multidrug-resistant bacteria (MDRB) contribute increasingly to morbidity, mortality, and healthcare costs. Extended-spectrum beta-lactam- and carbapenem-resistant Enterobacterales (ESBL-E and CRE) are MDRB of particular concern due to their ability to evolve into highly transmissible clones and acquire and spread antibiotic resistance determinants. Traditional epidemiological surveillance typically focuses on outbreaks of MDRB causing clinical infections, underestimating the burden of these pathogens within hospital systems. Broader efforts that account for asymptomatic carriage and environmental and community reservoirs would be ideal to track and mitigate the spread of MDRB. Wastewater surveillance has proven an effective tool for pathogen monitoring, as shown with SARS-CoV-2, but has not been established in clinical settings. This proposal will develop new systems to leverage wastewater for clinically applicable, proactive, and readily deployable MDRB monitoring. In Aim 1, we will establish standardized longitudinal surveillance strategies to inform infection control responses. We will use long-read metagenomics and novel bioinformatic approaches to rapidly identify significant changes in relative or absolute abundance of ESBL-E or CRE compared to site-specific baselines. We will also establish methods to translate wastewater testing data into interpretable “action thresholds” for use by hospital and clinical teams. In Aim 2, we will identify factors enabling the emergence of novel ESBL-E and CRE genotypes in the wastewater environment. Wastewater sampling can identify novel resistant genotypes before detection of clinical infections. We will further develop our novel Metapore-C technique to link bacterial hosts with resistance gene-harboring mobile elements and use this approach to identify environmental factors associated with acquisition of resistance, such as wastewater antibiotic levels and plumbing design. In Aim 3, we will devise wastewater testing methodologies suited to resource-limited settings. Standard wastewater testing approaches are often impractical or inadequate when access to resources or centralized wastewater treatment are limited, including for over 15% of the U.S. population not connected to public sewer lines. Our strategies for reducing per-sample costs and analytical burden, as piloted at a pediatric hospital in Gaborone, Botswana, will serve as a proof-of-concept for wastewater MDRB testing in diverse contexts including resource-limited areas, rural hospitals, and decentralized healthcare settings in the U.S. Overall, this project will significantly broaden the ability of wastewater surveillance to inform hospital and clinical care efforts, while establishing best practices for global surveillance of antimicrobial resistance in hospital wastewater.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $534,000 )
2026	2026	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	2	7/7/2026	NON-COMPETING CONTINUATION	$534,000
														Subtotal = $534,000

Issue Date FY: 2025 ( Subtotal = $534,000 )
2025	2025	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	1	7/23/2025	NEW	$534,000
														Subtotal = $534,000

Grand Total All Awards = $1,068,000

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Decoding multidrug-resistant pathogen dynamics for clinically-relevant wastewater surveillance

Award Number: DP2AI192737

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/23/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2030

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