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Model-informed cefepime dosing in paediatric patients receiving continuous renal replacement therapy
Ronaldo Morales Junior1, Shannon Reinert2, Emily Diseroad3
1Division of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Insights
Model-informed precision dosing (MIPD) optimized cefepime therapy for critically ill children on continuous renal replacement therapy (CRRT). This approach ensured effective antibiotic levels, avoiding toxicity and subtherapeutic exposures in pediatric CRRT patients.
Area of Science:
- Pediatric Critical Care Medicine
- Pharmacokinetics and Pharmacodynamics
- Renal Replacement Therapy
Background:
- Critically ill children on CRRT face unpredictable cefepime exposure due to altered pharmacokinetics.
- Subtherapeutic or toxic antibiotic levels can result from patient factors and CRRT parameters.
- Optimizing cefepime dosing is crucial for effective treatment in this vulnerable population.
Purpose of the Study:
- To describe the use of model-informed precision dosing (MIPD) for guiding cefepime therapy in pediatric patients undergoing CRRT.
- To assess the feasibility and clinical utility of MIPD in achieving therapeutic cefepime concentrations.
- To identify key factors influencing cefepime pharmacokinetics during CRRT.
Main Methods:
- A case series of five critically ill pediatric patients receiving cefepime and CRRT.
- Individual pharmacokinetic analyses using measured cefepime concentrations and a population PK model with a CRRT module.
- Inclusion of CRRT prescription variables (effluent flow rate, blood flow, filter type) in the PK model.
- Assessment of residual urine output and CRRT effluent flow rate as predictors of drug clearance.
Main Results:
- CRRT contributed significantly to total cefepime clearance (26.9%–83.4%) across cases.
- Residual urine output and CRRT effluent flow rate were identified as key predictors of cefepime clearance.
- Extended cefepime infusions were required in three patients to reach target pharmacodynamic goals.
- No patients required dose reduction due to concerns of excessive drug exposure.
Conclusions:
- MIPD is a feasible and clinically useful strategy for optimizing cefepime dosing in pediatric CRRT.
- Bedside pharmacokinetic consultation, incorporating patient-specific and CRRT factors, enhances cefepime therapy.
- This approach helps achieve therapeutic targets and avoid adverse antibiotic exposures in critically ill children on CRRT.
Abstract:
Critically ill children receiving β-lactam antibiotics while on continuous renal replacement therapy (CRRT) are at high risk of subtherapeutic or toxic antibiotic exposures due to patient-specific physiology and CRRT prescription parameters that influence drug pharmacokinetics. This case series describes the use of model-informed precision dosing (MIPD) to guide cefepime therapy in five critically ill paediatric patients receiving CRRT. Individual pharmacokinetic analyses were conducted using measured cefepime plasma concentrations and a previously published population PK model with a mechanistic CRRT module that incorporates CRRT prescription variables, including effluent flow rate, blood flow, and filter type. Residual urine output and CRRT effluent flow rate were found to be strong predictors of intrinsic and extracorporeal clearance, respectively. Across the five cases, CRRT accounted for 26.9% to 83.4% of total cefepime clearance. In three patients, extended infusion was necessary to achieve pharmacodynamic targets for efficacy. No patients required dose reduction to avoid excessive exposure. This series demonstrates the feasibility and clinical utility of bedside pharmacokinetic consultation using MIPD to guide cefepime dosing in paediatric CRRT, accounting for both patient-specific and therapy-related factors.
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