Ceftriaxone Pharmacokinetics and Pharmacodynamics in 2 Pediatric Patients on Extracorporeal Membrane Oxygenation Therapy.

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.