# Longitudinal Assessment of Beta-lactam Antibiotic Exposure in in Critically Ill Children with Sepsis in the PICU to Predict Dosing Requirements

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $629,372

## Abstract

Project Summary
Bacterial sepsis and septic shock are among the most common causes of admission to pediatric intensive care
units (PICU) in the United States. Morbidity and mortality remain high for neonates, infants and children with
increasingly complicated comorbidities (cancer, trauma, complex genetic and anatomic anomalies) with many
being immune compromised from breaches in anatomic barriers with catheters (intravenous, bladder,
pleural/mediastinal space, abdominal) as well as secondary to immune-ablative and immune-suppressive
therapy. All children who present to the PICU with sepsis syndrome receive empiric antimicrobial
therapy. Currently, doses of antimicrobial agents used for children in the PICU are based on pharmacokinetic
descriptions of drug distribution and elimination in children without severe infections; this population is usually
excluded from participation in FDA mandated clinical trials for safety and efficacy of new antibacterial agents.
For infants and children with bacterial sepsis, attaining an antimicrobial drug exposure that is
adequate for microbiologic and clinical cure is essential for survival. In these children, dramatic and
rapid changes in kidney function during the first days of hospitalization for sepsis based on changes in cardiac
output and organ perfusion can lead to increased or decreased renal elimination of antibiotics. Additional
reasons for inadequate antibiotic exposure include leakage of fluids and antibiotics into tissues (capillary leak
syndrome) and changes in circulating blood volume following massive intravenous fluid resuscitation (up to
100 mL/kg), not uncommon in septic shock.
We plan to analyze antibiotic exposure and renal function in critically ill children receiving FDA-approved doses
of a standard-of-care (SOC), generic beta-lactam antibiotic with broad spectrum antibacterial activity,
meropenem, focusing on each of the first 3 days of admission, when the most dramatic alterations in
physiology occur. By measuring plasma and urine concentrations in 50 children daily for the first 3 days in the
PICU, we can define the adequacy of beta-lactam exposure with current SOC therapy. We will create
pharmacokinetic-pharmacodynamic models, that can allow us to analyze physiologic factors, renal toxicity and
function, sepsis scores, and laboratory tests/biomarkers that may be associated with subtherapeutic or
potentially toxic exposures. Ultimately, we plan to present new antibiotic dosing guidelines for children with
sepsis in the PICU, with the potential to optimize daily dosing to save lives and decrease sepsis-mediated
morbidity.

## Key facts

- **NIH application ID:** 9961628
- **Project number:** 5R01HD095547-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** John S Bradley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $629,372
- **Award type:** 5
- **Project period:** 2018-07-28 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961628

## Citation

> US National Institutes of Health, RePORTER application 9961628, Longitudinal Assessment of Beta-lactam Antibiotic Exposure in in Critically Ill Children with Sepsis in the PICU to Predict Dosing Requirements (5R01HD095547-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9961628. Licensed CC0.

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