Beta-Lactam Antibiotic Exposure During Pediatric Extracorporeal Membrane Oxygenation: Retrospective Cohort Analysis of Drug Levels Using Standard Dosing, 2018-2020.

OBJECTIVES

Children on extracorporeal membrane oxygenation (ECMO) are at high risk of infection that may worsen prognosis. Even though treatment with beta-lactam antibiotics is frequent, dosing is not adapted to altered pharmacokinetic and pharmacodynamic characteristics of children on ECMO. There is, therefore, a risk of inadequate drug levels when using standard dosing. In this study, we aimed to describe beta-lactam exposures of children on ECMO using current dosing and to identify factors associated with inadequate exposure. The optimal pharmacokinetic/pharmacodynamic target was considered as a plasma concentration four times above the minimum inhibitory concentration throughout the dosing interval target.

DESIGN

Two-center retrospective cohort study.

SETTING

Two PICUs in Paris, France.

PATIENTS

Children (from birth to 18 yr) undergoing venovenous or venoarterial ECMO, from 2018 to 2020.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

There were 57 patients who received 11 different beta-lactams, with 226 plasma concentrations analyzed. A total of 32 infections were documented. Overall, 133 of 226 concentrations (58.8%) were insufficient, primarily in samples from children younger than 28 days (p = 0.035), with low body weight (p = 0.013), or in instances of hypoalbuminemia (p = 0.011) and increased renal clearance (p = 0.032). Supratherapeutic concentrations were observed in 25 of 226 samples (11.1%), associated with being taken from patients with renal impairment (p < 0.01).

CONCLUSIONS

In this retrospective cohort of pediatric ECMO cases, there is an associated risk of underexposure when prescribing conventional dosing of beta-lactams, which are likely associated with renal impairment and fluid overload. Prospective testing of therapeutic drug monitoring combined with pharmacokinetic/pharmacodynamic models should be tested as a risk-reduction strategy in this vulnerable population.