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Individual Meropenem Clearance in Infants on ECMO and CVVHDF is Difficult to Predict: A Case Report and Review of the
Ali Jabareen1,2, Laila Nassar2,3, Marina Karasik4
1From the Pharmacy Services, Rambam Health Care Campus, Haifa, Israel.
Insights
Meropenem clearance in critically ill neonates on ECMO and CRRT is lower than expected, necessitating therapeutic drug monitoring. Dosing adjustments are crucial for effective treatment in this vulnerable population.
Area of Science:
- Neonatal pharmacology
- Critical care medicine
- Pharmacokinetics
Background:
- Meropenem is a critical broad-spectrum antibiotic for neonatal sepsis.
- Pharmacokinetic data in critically ill neonates undergoing extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) are limited and conflicting.
- Understanding meropenem clearance is vital for optimizing treatment in this complex patient group.
Observation:
- A neonate with a diaphragmatic hernia required ECMO and continuous venovenous hemodiafiltration (CVVHDF) for sepsis and multiorgan failure.
- Meropenem was administered, with plasma concentrations measured during ECMO/CVVHDF and CVVHDF alone.
- The patient received a continuous infusion of meropenem at 240 mg/kg/day.
Findings:
- Meropenem clearance was measured at 1.9 and 2.6 mL/kg/min, which is substantially lower than previously reported in similar pediatric populations.
- Achieved meropenem serum concentrations (90 and 64 mg/L) significantly exceeded the therapeutic target of 10 mg/L.
- These findings highlight significant variability and reduced clearance in this specific neonatal context.
Implications:
- Meropenem clearance is unpredictable in neonates with compromised renal function, especially with ECMO and CRRT.
- Therapeutic drug monitoring of meropenem plasma concentrations is essential to guide dosing and ensure efficacy.
- Current dosing recommendations may not be generalizable, emphasizing the need for individualized treatment strategies.
Objectives:
Meropenem is a broad-spectrum carbapenem antibiotic with mostly renal excretion. Conflicting data are available regarding meropenem pharmacokinetics in critically ill neonates on concomitant continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO). Our objectives were to assess meropenem clearance in a neonate on CRRT and ECMO, compare it to previously published data and assess whether dose recommendations can be generalized in this population.
Case Description:
A 2.5 kg male infant with a large diaphragmatic hernia was delivered by cesarean section at week 35 and immediately mechanically ventilated due to shock and respiratory insufficiency. He underwent surgical correction of the hernia, but developed recurrent sepsis, multiorgan failure and pulmonary hypertension. He remained mechanically ventilated and required ECMO and continuous venovenous hemodiafiltration. He was started on meropenem 40 mg/kg/dose, every 8 hs for Enterobacter cloacae bacteremia and sepsis, but due to lack of clinical and microbiologic response despite in vitro susceptibility, he was started on a continuous meropenem infusion of 240 mg/kg/d, based on dose recommendations in a similar case. We measured steady state meropenem plasma concentrations on 2 occasions, during ECMO and continuous venovenous hemodiafiltration (CVVHDF) and then on CVVHDF only.
Results:
Meropenem serum concentrations were 90 and 64 mg/L on the first and second occasion (therapeutic target concentration, 10 mg/L) corresponding to a clearance of 1.9 and 2.6 mL/kg/min. This clearance estimate was substantially lower than that reported in toddlers on CRRT and ECMO in some studies.
Conclusion:
In neonates and infants, meropenem clearance is difficult to predict because of dynamic ontogenetic changes in renal function. This problem is further aggravated in acutely ill infants with decreased renal function, renal replacement therapy and/or ECMO. Therefore, Target Concentration Intervention based on meropenem plasma concentrations is indispensable to ensure therapeutic exposure in this population.
