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Ceftriaxone Pharmacokinetics and Pharmacodynamics in 2 Pediatric Patients on Extracorporeal Membrane Oxygenation
Francisco C Cervantes1, Tomoyuki Mizuno2,3, Min Dong2,3
1Department of Medical Education, University of Cincinnati College of Medicine, Cincinnati, Ohio. Arbough is now with the Department of Anesthesiology, University of Kentucky College of Medicine, Lexington, Kentucky.
Insights
Extracorporeal membrane oxygenation (ECMO) increases ceftriaxone clearance in critically ill children. Dosing every 12 hours maintained therapeutic levels, but precision dosing may optimize antibiotic effectiveness in pediatric ECMO patients.
Area of Science:
- Pediatric Critical Care Medicine
- Pharmacokinetics and Pharmacodynamics
- Infectious Disease Management
Background:
- Critically ill children with cardiac or respiratory failure may require extracorporeal membrane oxygenation (ECMO).
- Ceftriaxone is a commonly used antibiotic in critically ill patients, but its pharmacokinetics/pharmacodynamics (PK/PD) in pediatric ECMO patients are not well-studied.
- Understanding ceftriaxone PK/PD is crucial for effective infection management in this vulnerable population.
Observation:
- Two pediatric patients on ECMO were studied for ceftriaxone PK profiles using opportunistic sampling and Bayesian estimation.
- Patient 1 (venovenous ECMO) showed increased ceftriaxone clearance on ECMO (13.0 L/h/70 kg) compared to off ECMO (7.6 L/h/70 kg) and model predictions (6.54 L/h/70 kg).
- Patient 2 (venoarterial ECMO) had an estimated ceftriaxone clearance of 9.1 L/h/70 kg while on ECMO, with trough concentrations above the *Streptococcus pneumoniae* breakpoint.
Findings:
- Extracorporeal membrane oxygenation significantly increased ceftriaxone clearance in both pediatric patients compared to model-predicted values for critically ill children without ECMO.
- Twelve-hour dosing intervals maintained ceftriaxone concentrations above the breakpoint for common bacteria in both patients.
- However, concentrations did not consistently reach 4 times the breakpoint in one patient, indicating potential for sub-optimal dosing.
Implications:
- ECMO necessitates adjustments in ceftriaxone dosing strategies for pediatric patients to ensure adequate drug exposure.
- While 12-hour dosing may be sufficient for basic bacterial coverage, precision dosing is likely required to guarantee consistent attainment of therapeutic targets.
- Further research with larger cohorts is warranted to establish optimized ceftriaxone dosing regimens for pediatric ECMO patients.
Background:
Critically ill patients with cardiac or respiratory failure may require extracorporeal membrane oxygenation (ECMO). Antibiotics are frequently administered when the suspected cause of organ failure is an infection. Ceftriaxone, a β-lactam antibiotic, is commonly used in patients who are critically ill. Although studies in adults on ECMO have suggested minimal impact on ceftriaxone pharmacokinetics, limited research exists on ceftriaxone pharmacokinetics/pharmacodynamics (PK/PD) in pediatric ECMO patients. We report the PK profiles and target attainment of 2 pediatric patients on ECMO who received ceftriaxone.
Methods:
Ceftriaxone concentrations were measured in 2 pediatric patients on ECMO using scavenged opportunistic sampling. PK profiles were generated and individual PK parameters were estimated using measured free ceftriaxone concentrations and a published population PK model in children who are critically ill, using Bayesian estimation.
Results:
Patient 1, an 11-year-old boy on venovenous ECMO for respiratory failure received 2 doses of 52 mg/kg ceftriaxone 12 hours apart while on ECMO and additional doses every 12 hours off ECMO. On ECMO, ceftriaxone clearance was 13.0 L/h/70 kg compared with 7.6 L/h/70 kg off ECMO, whereas the model-predicted mean clearance in children who are critically ill without ECMO support was 6.54 L/h/70 kg. Patient 2, a 2-year-old boy on venoarterial ECMO due to cardiac arrest received 50 mg/kg ceftriaxone every 12 hours while on ECMO for >7 days. Only clearance while on ECMO could be estimated (9.1 L/h/70 kg). Trough concentrations in both patients were >1 mg/L (the breakpoint for Streptococcus pneumoniae ) while on ECMO.
Conclusions:
ECMO increased ceftriaxone clearance above the model-predicted clearances in the 2 pediatric patients studied. Twelve-hour dosing allowed concentrations to remain above the breakpoint for commonly targeted bacteria but not 4 times the breakpoint in one patient, suggesting that precision dosing may be beneficial to ensure target attainment in children on ECMO.
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