What is the recommended dose of meropenem (generic name) for pediatric patients, considering age, weight, and renal function?

Meropenem Dosing in Pediatric Patients

Standard Dosing Recommendations

For children 3 months and older with normal renal function, administer meropenem 20 mg/kg every 8 hours (maximum 1 gram per dose) for intra-abdominal infections and 10 mg/kg every 8 hours (maximum 500 mg per dose) for complicated skin and skin structure infections, with dose escalation to 20 mg/kg every 8 hours when treating Pseudomonas aeruginosa. 1

Age-Specific Dosing for Children ≥3 Months

• Complicated skin and skin structure infections: 10 mg/kg IV every 8 hours, up to maximum 500 mg per dose 1
• Intra-abdominal infections: 20 mg/kg IV every 8 hours, up to maximum 1 gram per dose 1
• Meningitis: 40 mg/kg IV every 8 hours, up to maximum 2 grams per dose 1
• Pseudomonas infections (skin/soft tissue): Increase to 20 mg/kg every 8 hours (or 1 gram for children >50 kg) 1

Neonatal and Young Infant Dosing (<3 Months)

For infants less than 3 months with complicated intra-abdominal infections, dosing depends on both gestational age (GA) and postnatal age (PNA): 1

• Infants <32 weeks GA and PNA <2 weeks: 20 mg/kg every 12 hours 1
• Infants <32 weeks GA and PNA ≥2 weeks: 20 mg/kg every 8 hours 1
• Infants ≥32 weeks GA and PNA <2 weeks: 20 mg/kg every 8 hours 1
• Infants ≥32 weeks GA and PNA ≥2 weeks: 30 mg/kg every 8 hours 1

The guideline for multidrug-resistant organisms provides alternative neonatal dosing based on gestational and postnatal age stratification: 2

• Gestational age <32 weeks, postnatal age <14 days: 20 mg/kg every 12 hours 2
• Gestational age <32 weeks, postnatal age ≥14 days: 20 mg/kg every 8 hours 2
• Gestational age ≥32 weeks, postnatal age <14 days: 20 mg/kg every 8 hours 2
• Gestational age ≥32 weeks, postnatal age ≥14 days: 30 mg/kg every 8 hours 2

Administration Guidelines

• Infusion duration: 15-30 minutes for standard dosing 1
• Neonates and young infants (<3 months): Administer over 30 minutes 1
• Bolus injection option (adults only): 3-5 minutes for 5-20 mL volumes 1

Renal Dose Adjustments

There is no established experience for dose adjustment in pediatric patients with renal impairment. 1 However, meropenem clearance is strongly associated with serum creatinine and postmenstrual age in infants. 3

For adult patients with renal impairment (which may guide decision-making in older adolescents approaching adult weight): 1

• CrCl >50 mL/min: Standard dose every 8 hours 1
• CrCl 26-50 mL/min: Standard dose every 12 hours 1
• CrCl 10-25 mL/min: Half the standard dose every 12 hours 1
• CrCl <10 mL/min: Half the standard dose every 24 hours 1

Weight-Based Dosing Thresholds

Children weighing more than 40 kg should receive adult dosing regimens rather than weight-based pediatric calculations. 4, 5 At exactly 40 kg, weight-based pediatric dosing provides more precision. 6

• Children >50 kg receiving meropenem for Pseudomonas skin infections: Use 1 gram every 8 hours instead of weight-based calculation 1

Critical Considerations for Optimal Dosing

Standard Dosing May Be Inadequate

Recent pharmacokinetic-pharmacodynamic studies reveal that FDA-approved dosing regimens fail to achieve therapeutic targets in a substantial proportion of children over 3 months of age, particularly for organisms with MIC values ≥2 mg/L. 7

• Only 68.4% of children >3 months and <50 kg achieved target exposures for MIC 2 mg/L 7
• Only 41.7% achieved targets for MIC 4 mg/L 7
• For children >50 kg, only 41.3% and 17% achieved these respective targets 7

Enhanced Dosing Strategies for Critically Ill Children

For critically ill infants and children in intensive care settings with severe infections: 8

• 40 mg/kg/dose every 8 hours as a 4-hour infusion achieves 87.5% and 68.6% probability of target attainment for MIC 1 and 2 μg/mL, respectively 8
• 110 mg/kg/day as continuous infusion achieves 98.0% and 73.3% probability for MIC 4 and 8 μg/mL 8
• Continuous infusion of 60-120 mg/kg/day is most adequate for achieving 50-100% fT>MIC targets, particularly for high MIC pathogens (>4 mg/L) 9

Pharmacokinetic Principles

Meropenem clearance in children is influenced by: 3

• Serum creatinine: Lower creatinine increases clearance 3
• Postmenstrual age: Clearance increases with maturation 3
• Body weight: Significantly correlates with clearance 8
• Estimated GFR: Higher eGFR increases clearance 9

Approximately 55% of administered meropenem is recovered unchanged in urine, indicating substantial renal elimination. 10

Common Pitfalls to Avoid

• Do not use age alone to determine adult versus pediatric dosing—the 40 kg weight threshold is the critical determinant 4, 5
• Do not assume standard dosing is adequate for Pseudomonas infections—these require higher doses (20 mg/kg vs 10 mg/kg for skin infections) 1
• Do not overlook the need for dose adjustment in neonates—gestational and postnatal age both impact clearance 1, 3
• Do not use adult renal dosing adjustments in children—there is insufficient pediatric data to guide this practice 1
• For critically ill children or those with high-MIC pathogens, consider extended infusion (4 hours) or continuous infusion strategies rather than standard 30-minute infusions to optimize time above MIC 8, 9