Utilizing Pharmacokinetic Modeling for Meropenem in Children With Sepsis

We are continuing our new series, Media Day, where we spotlight individual medical institutions and infectious disease (ID) programs. Today, we spotlight UC San Diego’s Skaggs School of Pharmacy and Pharmaceutical Sciences and the university’s extensive research programs and community-based health programs to serve the local population.

Jennifer Le, PharmD, MAS, FIDSA, FCCP, FCSHP, worked with a team of investigators including John Bradley, MD, that studied population-based pharmacokinetic modeling for meropenem in children with sepsis with varying renal function.

Their work was published earlier this year in the journal, Clinical Pharmacokinetics.

“We prospectively evaluated meropenem clearance (CLMERO) and volume of distribution (V1-MERO), innovativelyassessing renal biomarkers (serum creatinine [SCr], serum cystatin C [SCys], and neutrophil gelatinase-associated lipocalin [SNgal]), in infants aged ≥ 4 weeks and children on intravenous (IV) meropenem 20 mg/kg every 8 h from 2019 to 2023. Cases with sepsis were matched to controls without sepsis,” Le et al wrote.¹

Their analysis included 27 participants with 19 cases and 8 controls. Although this was a small trial, Le explained this was an inherently difficult group to study.

“It was one of the hardest models, because the patients we selected were on the extreme spectrum of renal function,” Le said to Contagion. “I had so much instability with the model that we created, and so we had to add more patient data to make something knowledgeable that we could export to and let others know.”

In terms of results, clearance and volume of distribution were significantly lower in children with sepsis compared with non-septic controls. “Meropenem clearance,V1-MERO and eGFR-MS were significantly decreased in cases versus controls, with higher variability of eGFR-MS in cases…Wide variation in meropenem concentrations in children with sepsis as compared to those without sepsis prompt close monitoring of GFR and drug concentrations in this population,” the authors wrote.¹

“If kidney function changes each day, the dose should be changing too, right? To accommodate that, it needs the kidney to clear the drug. So we conducted a prospective study getting samples, getting kids who were already on meropenem for a clinical indication, and we were able to see huge variation in meropenem clearance between kids who are septic vs not. And it's not only different between children, it's different within that same child,” Le said.

In terms of their study’s approach, she found pharmacokinetic modeling advantageous to create some clinical takeaways including the following:

· Standard dosing (20 mg/kg q8h) may not reliably achieve therapeutic exposure in this population.

· Close monitoring of kidney function and possibly drug levels (therapeutic drug monitoring, TDM) is needed, especially during the dynamic early phase of septic shock.

· Biomarkers beyond creatinine (like cystatin C, NGAL) could improve dosing precision.¹

“That's the beauty of population-based pharmacokinetic modeling; you can actually get an estimation of that variation within that patient, whereas a lot of other types of pharmacokinetic analysis doesn't do that, so we're able to see the trends.”

In the next episode, UC San Diego's Nimish Patel, PharmD, offers his insights on his approach to prescribing HIV PrEP and clinical management of this form of prophylaxis.

Reference
1. Le J, Huynh J, Vo B, et al. Variability in Meropenem Distribution and Clearance in Children with Sepsis: Population-Based Pharmacokinetics with Assessment of Renal Biomarkers. Clin Pharmacokinet. 2025;64(5):769-777. doi:10.1007/s40262-025-01495-3