Evidence map›Paper›PMID 39988706›Full record

ArticleClinical pharmacokinetics2025

Population Pharmacokinetics of Cefepime in Critically Ill Children and Young Adults: Model Development and External Validation for Monte Carlo Simulations and Model-Informed Precision Dosing.

Ronaldo Morales Junior, H Rhodes Hambrick, Tomoyuki Mizuno, Kathryn E Pavia, Kelli M Paice, Peter Tang, Erin Schuler, Kelli A Krallman, Luana Johnson, Michaela Collins and 5 more

Abstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Ronaldo Morales JuniorDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 6018, Cincinnati, OH, USA. morales.ronaldo@gmail.com.ORCID 0000-0002-5856-3717
H Rhodes HambrickDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 6018, Cincinnati, OH, USA.
Tomoyuki MizunoDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 6018, Cincinnati, OH, USA.
Kathryn E PaviaDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 6018, Cincinnati, OH, USA.
Kelli M PaiceDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 6018, Cincinnati, OH, USA.
Peter TangDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Erin SchulerDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Kelli A KrallmanCenter for Acute Care Nephrology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Luana JohnsonCenter for Acute Care Nephrology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Michaela CollinsCenter for Acute Care Nephrology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Abigayle GibsonDivision of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Calise CurryDivision of Hospital Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Jennifer KaplanDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Stuart GoldsteinDivision of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Sonya Tang GirdwoodDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 6018, Cincinnati, OH, USA.

Funding

T32 Cincinnati Pediatric Clinical Pharmacology Training ProgramT32HD069054 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI TRACY A GLAUSER, Sonya C Tang Girdwood · 2011 to 2026
$3.0M
RESEARCH TRAINING IN PEDIATRIC NEPHROLOGYT32DK007695 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI DEVARAJAN, PRASAD · 1992 to 2023
$2.2M
Antibiotic Model-Informed Precision Dosing in Critical IllnessR35GM146701 · NIGMS · CINCINNATI CHILDRENS HOSP MED CTR · PI Sonya C Tang Girdwood · 2022 to 2026
$2.0M
Eunice Kennedy Shriver National Institute of Child Health and Human Development T32HD069054NICHD NIH HHS T32 HD069054NIDDK NIH HHS T32 DK007695NIDDK NIH HHS T32DK007695NIGMS NIH HHS R35 GM146701NIGMS NIH HHS R35GM146701
6 · The paper itself

Abstract

BACKGROUND AND

objectiveThis study aimed to develop a population pharmacokinetic model for cefepime in critically ill pediatric and young adult patients to inform dosing recommendations and to evaluate the model's predictive performance for model-informed precision dosing.

methodsPatients in the pediatric intensive care unit receiving cefepime were prospectively enrolled for clinical data collection and opportunistic plasma sampling for cefepime concentrations. Nonlinear mixed effects modeling was conducted using NONMEM. Allometric body weight scaling was included as a covariate with fixed exponents. Monte Carlo simulations determined optimal initial dosing regimens against susceptible pathogens. The model's predictions were evaluated with an external dataset.

resultsData from 510 samples across 100 patients were best fit with a two-compartment model with first-order elimination. Estimated glomerular filtration rate and cumulative percentage of fluid balance were identified as significant covariates on clearance and central volume of distribution, respectively. Internal validation showed no model misspecification. External validation confirmed that bias and precision for both population and individual predictions were within commonly accepted ranges. Monte Carlo simulations suggested that the usual dose of 50 mg/kg may require a 3-h infusion or a 6-h dosing interval to keep concentrations above the Pseudomonas aeruginosa minimum inhibitory concentration (≤ 8 mg/L) throughout the dosing interval for patients with normal or augmented renal clearance.

conclusionA cefepime population pharmacokinetic model for critically ill pediatric patients was successfully developed, accounting for patient renal function, fluid status, and body size, using real-world data. The model was internally and externally validated for use in optimal dosing simulations and model-informed precision dosing.

Indexed as

Anti-Bacterial AgentsCefepimeModels, BiologicalAdolescentChildChild, PreschoolCritical IllnessFemaleHumansInfantIntensive Care Units, PediatricMaleMonte Carlo MethodProspective StudiesYoung AdultAnti-Bacterial AgentsCefepime

Identifiers

PMID39988706
PMCPMC12041147

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.