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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
A Real-Life Study of Prolonged Meropenem Infusion in Neonates and Children Admitted to Intensive Care Units: Are
Marcello Mariani1, Marco Scaglione2, Chiara Russo2
1Pediatric Infectious Diseases Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.
Insights
Meropenem dosing in critically ill children often fails to reach therapeutic targets. Higher doses and longer infusions may be needed to combat resistant Gram-negative infections in pediatric patients.
Area of Science:
- Pediatric Pharmacology
- Infectious Diseases
- Critical Care Medicine
Background:
- Meropenem is vital for treating resistant Gram-negative infections in children.
- Current dosing may not achieve optimal pharmacokinetic targets in critically ill pediatric patients.
Purpose of the Study:
- To evaluate meropenem pharmacokinetic targets in pediatric intensive care unit patients.
- To identify factors influencing meropenem trough concentrations in pediatric patients.
Main Methods:
- Retrospective cohort study of 86 pediatric patients (<18 years) in NICU/PICU.
- Analysis of 97 meropenem plasma levels, focusing on trough concentrations (C trough).
- Assessment of demographic, clinical, and pharmacokinetic parameters, including estimated glomerular filtration rate (eGFR).
Main Results:
- Median C trough was 2.8 mg/L, significantly lower than the target of >8 mg/L in most patients (only 27.8% achieved target).
- Neonates had higher C trough (8.9 mg/L) than older children (2.2 mg/L).
- Lower eGFR was associated with achieving higher C trough levels (p=0.001).
Conclusions:
- Current meropenem dosing may be inadequate for critically ill pediatric patients, especially those with augmented renal clearance.
- Increased dosages and prolonged infusion times may enhance efficacy against resistant Gram-negative bacteria.
- Further research is needed to optimize meropenem dosing strategies in pediatric critical care.
Abstract:
Background/Objectives: Meropenem is a broad-spectrum antibiotic essential for treating resistant Gram-negative infections in pediatric patients. Current dosing recommendations may not consistently achieve optimal pharmacokinetic (PK) targets, especially in critically ill children. Methods: We conducted a retrospective cohort study at IRCCS Istituto Giannina Gaslini, analyzing 97 plasma levels from 86 pediatric patients (<18 years) hospitalized between January 2020 and December 2023 in the neonatal and pediatric intensive care unit. Patients receiving meropenem for proven or suspected infections were included. Demographic, clinical, and PK parameters were assessed, with a focus on trough concentrations (Ctrough). Results: The median age was 25 months, with neonates representing 15.5% of cases. The median Ctrough was 2.8 mg/L and was significantly higher in neonates (8.9 mg/L) compared to older patients (2.2 mg/L, p < 0.001). Only 27.8% of patients achieved the target Ctrough of >8 mg/L, with estimated glomerular filtration rate (eGFR) being the primary factor influencing these levels. Patients with Ctrough > 8 mg/L had a significantly lower eGFR (61 mL/min/1.73 m2) compared to those below this threshold (131 mL/min/1.73 m2, p = 0.001). Conclusions: The current meropenem dosing regimen may not reliably meet PK targets in critically ill pediatric patients, particularly those with augmented renal clearance or when treating pathogens with increased meropenem MIC. Our findings suggest that increased dosages and prolonged infusion times may be necessary to optimize therapeutic efficacy against resistant Gram-negative bacteria in this vulnerable population. Further studies are needed to refine dosing strategies and improve patient outcomes.
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