Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Development and Evaluation of CRRT-Specific Precision Dosing Models to Optimize Beta-Lactam Treatment for Patients with Hospital-Acquired Pneumonia

Award Number: R21AI174159
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: 06/23/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2026

Group Awards By:

View Award Description

Development and Evaluation of CRRT-Specific Precision Dosing Models to Optimize Beta-Lactam Treatment for Patients with Hospital-Acquired Pneumonia - Project Abstract Hospital-acquired pneumonia (HAP) caused by antibiotic-resistant pathogens such as Klebsiella aerogenes, Klebsiella pneumoniae, and Pseudomonas aeruginosa are responsible treatment failure and mortality rates up to 50% and 30%, respectively. Meropenem is a mainstay for the treatment of HAP, but antibiotic resistance continues to erode its clinical efficacy. Importantly, the efficacy of beta-lactams depends on achieving adequate pharmacokinetic-pharmacodynamic (PK/PD) exposures; however, many patients with HAP experience inadequate PK/PD because of changes in PK caused by critically illness. Precision Dosing strategies can overcome PK variability caused by critical illness, but Precision Dosing requires robust models; such models for critically ill patients who develop kidney injury and require continuous renal replacement therapy (CRRT) are currently lacking for HAP patients. Without Precision Dosing models to help guide antibiotic dosing, these vulnerable patients will continue to experience high rates of treatment failure and death. Whereas the status quo treatment of HAP patients requiring CRRT uses population-based dosing schemes, our proposal will innovate Precision Dosing (i.e., individualized) strategies for patients with HAP. We will leverage the infrastructure of the Successful Clinical Response In Pneumonia Therapy (SCRIPT) Systems Biology Center to robustly address the unmet needs of patients on CRRT. Our long-term goal is to develop Precision Dosing strategies that overcome PK variability caused by severe illness. The project objective is to utilize the infrastructure, samples, and data collected in SCRIPT to develop Precision Dosing models for HAP. Our central hypothesis is: (1) CRRT leads to variability in beta-lactam PK with standard “one-size-fits all” HAP dosing regimens which (2) increases the risk of clinical treatment failure in HAP, (3) requiring Precision Dosing schemes. The rationale for our study is that Precision Dosing is needed for CRRT patients with HAP and that these approaches must be translated clinically. In Aim 1, we will develop and qualify Precision Dosing models for meropenem in CRRT. In Aim 2, we will describe meropenem PK/PD target attainment in plasma and in the lung for patients requiring CRRT. In Aim 3, we will create a web-based dosing calculator for translation to practice. Our study will have a positive clinical impact by providing clinicians with the tools necessary to ensure that each patient’s dosing is optimized. This research is significant because it addresses a critical unmet need for optimized therapy. Upon completion, our study will have robustly characterized alveolar PK in CRRT patients, filling a gap in the rigor of prior research. We will have translated our Precision Dosing model predictions into actionable dosing regimens, which is innovative as no such calculators exist. Our Precision Dosing calculator will be evaluated in a future R01-funded randomized controlled trial.


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: 2024 ( Subtotal = $151,881 )
2024	2024	MIDWESTERN UNIVERSITY	555 31ST ST	DOWNERS GROVE	IL	60515	DUPAGE	USA	Allergy and Infectious Diseases Research	000	2	6/5/2024	NON-COMPETING CONTINUATION	$151,881
														Subtotal = $151,881

Issue Date FY: 2023 ( Subtotal = $265,427 )
2023	2023	MIDWESTERN UNIVERSITY	555 31ST ST	DOWNERS GROVE	IL	60515	DUPAGE	USA	Allergy and Infectious Diseases Research	000	1	6/23/2023	NEW	$265,427
														Subtotal = $265,427

Grand Total All Awards = $417,308

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Development and Evaluation of CRRT-Specific Precision Dosing Models to Optimize Beta-Lactam Treatment for Patients with Hospital-Acquired Pneumonia

Award Number: R21AI174159

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: 06/23/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer