# Optimizing Vancomycin Therapy in Children

> **NIH NIH K23** · CHILDREN'S HOSP OF PHILADELPHIA · 2022 · $149,358

## Abstract

PROJECT SUMMARY/ABSTRACT
The candidate for this K23 Career Development Award, Kevin J. Downes, MD is a pediatric infectious diseases
specialist with training in pediatric clinical pharmacology and a background in clinical research focusing on
antimicrobial pharmacokinetics/pharmacodynamics (PK/PD) and antibiotic-associated acute kidney injury
(AKI). Dr. Downes' long-term career goal is to become an independent investigator with expertise in both
pharmacometrics and clinical trials. The proposed mentored research and career development plan promote
this career goal by facilitating Dr. Downes' short-term goal to obtain didactic and experiential training in
parametric and nonparametric population PK modeling and simulation, Bayesian adaptive control, and clinical
trial design. He has assembled a strong team of mentors led by Athena Zuppa MD, MSCE (primary mentor)
and Theoklis Zaoutis, MD, MSCE (co-mentor). His multidisciplinary mentorship team, comprised of national
experts in clinical pharmacology, infectious diseases, nephrology, and critical care medicine, combined with
the exceptional research environment of the Children's Hospital of Philadelphia and the University of
Pennsylvania, will provide the resources and content expertise to ensure success of the proposed research
and facilitate transition to academic independence.
The proposed project seeks to improve the safety and efficacy of intravenous (IV) vancomycin administration in
critically children by developing an approach to provide personalized, target-oriented vancomycin dosing. This
proposal will involve a series of related prospective studies that will result in the development and
implementation of an effective Bayesian dosing strategy to target vancomycin area under the curve (AUC24) in
critically ill children. Aim 1 will generate a population PK model for IV vancomycin, incorporating novel kidney
injury biomarkers as covariates. Aim 2 will identify the optimal sampling time to estimate AUC24 using Bayesian
estimation (Aim 2A) and then validate the optimal sampling time (Aim 2B) in a separate cohort of children. Aim
3 will pilot the feasability of Bayesian dosing to attain a targeted AUC24 goal in critically ill pediatric patients
using real-time biomarker and vancomycin measurement and dosing adjustments. This proposal, combined
with didactic training and strong mentorship in pharmacometrics and clinical research, will provide Dr. Downes
with the foundation for an independent research career in pediatric clinical pharmacology and infectious
diseases. This research will lead to development of future trials that investigate the ability of personalized
antimicrobial dosing and selection to maximize treatment efficacy, decrease toxicity, and minimize the
development of resistance in children receiving vancomycin. The skills learned during this career development
award will be generalizable to the study of other antimicrobial agents and pediatric populations.

## Key facts

- **NIH application ID:** 10438596
- **Project number:** 5K23HD091365-05
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Kevin James Downes
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $149,358
- **Award type:** 5
- **Project period:** 2018-07-10 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438596

## Citation

> US National Institutes of Health, RePORTER application 10438596, Optimizing Vancomycin Therapy in Children (5K23HD091365-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10438596. Licensed CC0.

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