What is the recommended dose of Meropenem (generic name) for neonates?

From the Guidelines

Meropenem dosing for neonates should be 20 mg/kg/dose given intravenously, with frequency adjusted based on gestational and postnatal age, as recommended by the most recent guidelines 1.

Meropenem Dosing Recommendations

The dosing frequency for meropenem in neonates varies based on gestational age and postnatal age.

• For gestational age less than 32 weeks, administer meropenem every 12 hours in the first 14 days of life, then every 8 hours thereafter 1.
• For gestational age 32 weeks or older, give meropenem every 8 hours in the first 14 days, then every 8 hours subsequently 1.

Important Considerations

• For severe infections like meningitis, consider using the higher end of the dosing range, although specific recommendations for meningitis are not provided in the most recent guidelines 1.
• Meropenem should be infused over 30 minutes, or over 4 hours for meningitis to maximize time above MIC, although this is not explicitly stated in the provided guidelines.
• Monitor renal function and adjust dosing in renal impairment, as meropenem is primarily excreted by the kidneys.

Rationale for Meropenem Use

Meropenem is preferred in neonates due to its broad spectrum activity against gram-positive, gram-negative, and anaerobic bacteria, good CNS penetration, and favorable safety profile with lower seizure risk compared to other carbapenems 1.

• It has minimal drug interactions and is generally well-tolerated in this vulnerable population, making it suitable for empiric therapy in suspected serious bacterial infections in neonates.
• The most recent guidelines from 2022 1 provide the best evidence for meropenem dosing in neonates, superseding older recommendations.

From the FDA Drug Label

For pediatric patients (with normal renal function) less than 3 months of age, with complicated intra-abdominal infections, the meropenem for injection dose is based on gestational age (GA) and postnatal age (PNA).

Table 3: Recommended Meropenem for Injection Dosage Schedule for Pediatric Patients Less than3 Months of Age with Complicated Intra-abdominal Infections and Normal Renal Function Age Group Dose (mg/kg) Dose Interval Infants less than 32 weeks GA and PNA less than 2 weeks 20 Every 12 hours Infants less than 32 weeks GA and PNA 2 weeks and older 20 Every 8 hours Infants 32 weeks and older GA and PNA less than 2 weeks 20 Every 8 hours Infants 32 weeks and older GA and PNA 2 weeks and older 30 Every 8 hours

The recommended dose of meropenem in neonates is based on gestational age (GA) and postnatal age (PNA), with doses ranging from 20 mg/kg every 12 hours to 30 mg/kg every 8 hours for complicated intra-abdominal infections, as outlined in Table 3 2.

From the Research

Meropenem Dosing in Neonates

• The dosage of meropenem in neonates varies based on factors such as gestational age, postconceptional age, and serum creatinine levels 3.
• A study found that a dosage of 20 mg/kg every 8 hours achieved the desired pharmacodynamic target in 95% of preterm neonates and 91% of term neonates against Pseudomonas aeruginosa 3.
• Another study suggested that meropenem clearance is difficult to predict in neonates on continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO), and recommended target concentration intervention based on meropenem plasma concentrations 4.
• A case series reported the use of meropenem in 26 neonates with severe infections, with a dosage of 20 mg/kg every 12 hours (every 8 hours in Pseudomonas Aeruginosa infections), and found no adverse effects and a good clinical and bacterial response in all cases but one 5.
• A randomized controlled trial compared conventional versus prolonged infusion of meropenem in neonates with Gram-negative late-onset sepsis, and found that prolonged infusion resulted in higher clinical and microbiologic efficacy, and less adverse effects 6.
• A population pharmacokinetic study characterized meropenem pharmacokinetics in neonates and determined effective dosing recommendations, suggesting that doses should be adjusted based on creatinine clearance and body surface area 7.

Factors Affecting Meropenem Dosing

• Gestational age: Meropenem clearance is greater in neonates with older chronologic ages and in those born at later gestational ages 3.
• Postconceptional age: Postconceptional age is a predictor of meropenem elimination, with older postconceptional age associated with greater clearance 3.
• Serum creatinine levels: Serum creatinine is a predictor of meropenem elimination, with higher serum creatinine levels associated with lower clearance 3, 7.
• Continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO): Meropenem clearance is difficult to predict in neonates on CRRT and/or ECMO, and target concentration intervention is recommended 4.