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Updated: Jul 23, 2025
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Cefepime pharmacokinetics in critically ill children and young adults undergoing continuous kidney replacement
Kathryn Pavia1,2, H Rhodes Hambrick2,3, Kelli Paice1,2
1Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Insights
Cefepime dosing in critically ill children on continuous kidney replacement therapy (CKRT) requires careful consideration. While standard doses achieved targets against some bacteria, higher targets were often missed, suggesting a need for precision dosing.
Area of Science:
- Pediatric critical care medicine
- Pharmacokinetics and pharmacodynamics
- Infectious disease management
Background:
- Cefepime is a crucial antibiotic for treating sepsis in critically ill children.
- Renal excretion is the primary elimination pathway for cefepime.
- Dosing adjustments are necessary for pediatric patients with impaired kidney function or on continuous kidney replacement therapy (CKRT).
Purpose of the Study:
- To characterize the pharmacokinetic (PK) profile of cefepime in critically ill pediatric patients undergoing CKRT.
- To evaluate cefepime target attainment in this specific patient population.
Main Methods:
- A pharmacokinetic/pharmacodynamic (PK/PD) study of beta-lactam antibiotics identified eligible patients.
- Included were pediatric patients on CKRT for at least 24 hours who received at least two cefepime doses.
- PK parameters were determined using Bayesian estimation with a pediatric population PK model (MwPharm++).
- Target attainment was defined as the time of free cefepime concentrations above the minimum inhibitory concentration (MIC).
Main Results:
- Seven pediatric patients (ages 2-20 years) were analyzed, with CKRT indicated for renal failure, liver failure, or fluid overload.
- Effluent flow rates varied, but cefepime clearance and time above MIC (T>MIC) were comparable to previously published pediatric data.
- All patients achieved 100% T>MIC against Pseudomonas aeruginosa at 1x MIC, but only one patient reached 100% T>MIC at 4x MIC.
Conclusions:
- Most critically ill pediatric patients on CKRT did not achieve the stringent target of 100% free cefepime concentration above 4x MIC.
- Model-informed precision dosing strategies may be beneficial for optimizing cefepime therapy in this vulnerable population.
Objectives:
Cefepime is an antibiotic commonly used to treat sepsis and is cleared by renal excretion. Cefepime dosing requires adjustment in patients with decreased kidney function and in those receiving continuous kidney replacement therapy (CKRT). We aimed to characterize cefepime PK in a diverse cohort of critically ill paediatric patients on CKRT.
Methods:
Patients were identified from an ongoing pharmacokinetic/pharmacodynamic (PK/PD) study of beta-lactam antibiotics, and were included if they had received at least two cefepime doses in the ICU and were on CKRT for at least 24 h. PK parameters were estimated using MwPharm++ with Bayesian estimation and a paediatric population PK model. Target attainment was assessed as time of free cefepime concentrations above minimum inhibitory concentration (fT > 1× or 4 × MIC).
Results:
Seven patients were included in the study (ages 2 to 20 years). CKRT indications included liver failure (n = 1), renal failure (n = 4) and fluid overload (n = 2). Total effluent flow rates ranged from 1833 to 3115 (mean 2603) mL/1.73 m2/h, while clearance was 2.11-3.70 (mean 3.0) L/h/70 kg. Effluent flows were lower, but clearance and fT > MIC were similar to paediatric data published previously. Using Pseudomonas aeruginosa MIC breakpoints, all patients had 100% of dosing interval above MIC, but only one had 100% of dosing interval above 4× MIC.
Conclusions:
Since most patients failed to attain stringent targets of 100% fT > 4× MIC, model-informed precision dosing may benefit such patients.
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