Cefepime Dose Individualization in Early Sepsis: A Pragmatic Feasibility Trial Protocol
Abstract
IMPORTANCE:: Cefepime is a core antibiotic in sepsis treatment, yet standard dosing yields 10- to 30-fold exposure variability in critical illness. In the early “golden hours” of sepsis, low cefepime levels (affecting up to 70% of cases) may lead to organ dysfunction progression, treatment failure, and antimicrobial resistance. Empiric dose escalation to overcome low levels can increase the risk of dose-dependent neurotoxicity. We developed and qualified a population pharmacokinetic model using patient weight and estimated glomerular filtration rate from creatinine and cystatin C that, in simulation, improved attainment of effective and safe drug levels.
OBJECTIVES:: To describe the Beta-Lactam Optimization and Outcomes Management (BLOOM) 1 pragmatic feasibility trial.
DESIGN, SETTING, AND PARTICIPANTS:: This single-center, cluster-randomized, pragmatic feasibility trial (ClinicalTrials.gov: NCT07287332) was approved with a waiver of informed consent. Participants are critically ill adults (age ≥ 18 yr), hospitalized at Mayo Clinic (Rochester, MN), who are receiving cefepime for suspected or documented sepsis. A screening tool embedded in the electronic health record (EHR) identifies eligible patients newly initiated on cefepime (≤ 1 previous dose in 48 hr) who are then randomized to care groups (clusters) that use an individualized dosing algorithm (intervention) or usual-care dosing (control). Exclusions are cephalosporin allergy, acute kidney injury, kidney replacement therapy, extracorporeal membrane oxygenation, and missing inputs required for the algorithm (weight, creatinine, cystatin C). Recruitment began on January 15, 2026, and is expected to conclude by January 2027 (target enrollment, ≥ 300 patients).
INTERVENTIONS, OUTCOMES, AND ANALYSIS:: For eligible patients, EHR-embedded clinical decision support prompts the cluster-assigned dosing approach, with final dose decisions made by the clinical team. Feasibility, fidelity, and exploratory pharmacokinetic and clinical outcomes will be assessed using mixed methods.
CONCLUSIONS:: This workflow-integrated pragmatic feasibility trial will determine whether personalized cefepime dosing can be implemented in routine practice to optimize timely sepsis therapy while maintaining safety.
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BibTeX
@article{may2026cefepime,
title = {{Cefepime Dose Individualization in Early Sepsis: A Pragmatic Feasibility Trial Protocol}},
author = {Heather P. May and Andrew D. Rule and Phillip J. Schulte and Mohamed A. Addani and Kristin C. Cole and Ingrid M. Curran and Gerald W. Flaby and Ognjen Gajic and Paul J. Jannetto and Victor Montori and Yewande Odeyemi and Michael A. Rankin and Marc H. Scheetz and Sophia A. Steiner and Erin F. Barreto and for the Beta-Lactam Optimization and Outcomes Management (BLOOM) Study Group Beta-Lactam Optimization and Outcomes Management (BLOOM) Study Group membersPharmacy Services(May, Rankin, Addani, Curran, Steiner, and Barreto)Division of Nephrology and Hypertension(Rule and Barreto)Division of Epidemiology(Rule)Division of Clinical Trials and Biostatistics(Schulte and Cole)Anesthesia Research(Flaby)Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine(Gajic and Odeyemi)Department of Laboratory Medicine and Pathology(Jannetto)Knowledge and Evaluation Research Unit(Montori and Barreto)Mayo Clinic, Rochester, MN; Department of Pharmacy Practice(Scheetz)College of Pharmacy, Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, IL; and Department of Pharmacy(Scheetz)Northwestern Medicine, Chicago, IL},
journal = {Critical Care Explorations},
year = {2026},
month = nov,
doi = {10.1097/cce.0000000000001502},
url = {https://doi.org/10.1097/cce.0000000000001502},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Cefepime Dose Individualization in Early Sepsis: A Pragmatic Feasibility Trial Protocol
AU - Heather P. May
AU - Andrew D. Rule
AU - Phillip J. Schulte
AU - Mohamed A. Addani
AU - Kristin C. Cole
AU - Ingrid M. Curran
AU - Gerald W. Flaby
AU - Ognjen Gajic
AU - Paul J. Jannetto
AU - Victor Montori
AU - Yewande Odeyemi
AU - Michael A. Rankin
AU - Marc H. Scheetz
AU - Sophia A. Steiner
AU - Erin F. Barreto
AU - for the Beta-Lactam Optimization and Outcomes Management (BLOOM) Study Group Beta-Lactam Optimization and Outcomes Management (BLOOM) Study Group membersPharmacy Services(May, Rankin, Addani, Curran, Steiner, and Barreto)Division of Nephrology and Hypertension(Rule and Barreto)Division of Epidemiology(Rule)Division of Clinical Trials and Biostatistics(Schulte and Cole)Anesthesia Research(Flaby)Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine(Gajic and Odeyemi)Department of Laboratory Medicine and Pathology(Jannetto)Knowledge and Evaluation Research Unit(Montori and Barreto)Mayo Clinic, Rochester, MN; Department of Pharmacy Practice(Scheetz)College of Pharmacy, Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, IL; and Department of Pharmacy(Scheetz)Northwestern Medicine, Chicago, IL
PY - 2026
DA - 2026/11/01
JO - Critical Care Explorations
DO - 10.1097/cce.0000000000001502
UR - https://doi.org/10.1097/cce.0000000000001502
AB - IMPORTANCE:: Cefepime is a core antibiotic in sepsis treatment, yet standard dosing yields 10- to 30-fold exposure variability in critical illness. In the early “golden hours” of sepsis, low cefepime levels (affecting up to 70% of cases) may lead to organ dysfunction progression, treatment failure, and antimicrobial resistance. Empiric dose escalation to overcome low levels can increase the risk of dose-dependent neurotoxicity. We developed and qualified a population pharmacokinetic model using patient weight and estimated glomerular filtration rate from creatinine and cystatin C that, in simulation, improved attainment of effective and safe drug levels. OBJECTIVES:: To describe the Beta-Lactam Optimization and Outcomes Management (BLOOM) 1 pragmatic feasibility trial. DESIGN, SETTING, AND PARTICIPANTS:: This single-center, cluster-randomized, pragmatic feasibility trial (ClinicalTrials.gov: NCT07287332) was approved with a waiver of informed consent. Participants are critically ill adults (age ≥ 18 yr), hospitalized at Mayo Clinic (Rochester, MN), who are receiving cefepime for suspected or documented sepsis. A screening tool embedded in the electronic health record (EHR) identifies eligible patients newly initiated on cefepime (≤ 1 previous dose in 48 hr) who are then randomized to care groups (clusters) that use an individualized dosing algorithm (intervention) or usual-care dosing (control). Exclusions are cephalosporin allergy, acute kidney injury, kidney replacement therapy, extracorporeal membrane oxygenation, and missing inputs required for the algorithm (weight, creatinine, cystatin C). Recruitment began on January 15, 2026, and is expected to conclude by January 2027 (target enrollment, ≥ 300 patients). INTERVENTIONS, OUTCOMES, AND ANALYSIS:: For eligible patients, EHR-embedded clinical decision support prompts the cluster-assigned dosing approach, with final dose decisions made by the clinical team. Feasibility, fidelity, and exploratory pharmacokinetic and clinical outcomes will be assessed using mixed methods. CONCLUSIONS:: This workflow-integrated pragmatic feasibility trial will determine whether personalized cefepime dosing can be implemented in routine practice to optimize timely sepsis therapy while maintaining safety.
SN - 2639-8028
ER -