What is the recommended infusion time and dosing regimen for meropenem in adults (including adjustments for renal impairment and severe infections) and in pediatric patients?

Meropenem Infusion: Dosing and Administration Guidelines

Standard Adult Dosing

For adults with normal renal function, administer meropenem 500 mg IV every 8 hours for skin and soft tissue infections, or 1 gram IV every 8 hours for intra-abdominal infections, infused over 15-30 minutes. 1

• For complicated skin and soft tissue infections caused by P. aeruginosa, increase the dose to 1 gram every 8 hours 1
• Doses of 1 gram may alternatively be administered as an IV bolus injection over 3-5 minutes 1
• The standard infusion time of 15-30 minutes is recommended for optimal pharmacokinetics, though bolus administration is acceptable for 1 gram doses 1

Dosing Adjustments for Renal Impairment

Dosage reduction is mandatory when creatinine clearance falls below 50 mL/min to prevent drug accumulation and toxicity. 1

Renal Dosing Algorithm:

• CrCl >50 mL/min: Standard dose (500 mg or 1 gram) 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

The terminal half-life of meropenem increases dramatically with renal impairment, from 1.2 hours in normal function to 10-13.7 hours in end-stage renal disease 2, 3. This prolongation necessitates the dosing adjustments above to maintain therapeutic concentrations without toxicity.

Hemodialysis Considerations:

• Meropenem is effectively removed by hemodialysis, with dialysis clearance of approximately 79-81 mL/min 2, 3
• Administer the dose after dialysis sessions to avoid premature drug removal 4
• Approximately 50% of meropenem is eliminated during intermittent hemodialysis 5
• There is inadequate information for specific dosing recommendations in patients on hemodialysis or peritoneal dialysis, though the drug is dialyzable 1

Continuous Renal Replacement Therapy (CRRT):

• For patients on CVVHDF, administer 1 gram IV every 12 hours as the initial dose 6
• Meropenem clearance during CVVHDF is approximately 129-141 mL/min 6
• CVVHF removes 25-50% of meropenem, while CVVHDF removes 13-53% depending on treatment parameters 5
• The significant variability in drug removal across different CRRT modalities creates risk of underdosing; err on the side of higher dosing given meropenem's excellent tolerability profile 5

Pediatric Dosing

Children ≥3 Months of Age:

Dose meropenem based on infection type: 10 mg/kg every 8 hours for skin infections, 20 mg/kg every 8 hours for intra-abdominal infections, or 40 mg/kg every 8 hours for meningitis (maximum 2 grams per dose). 1

• For children weighing >50 kg, use adult dosing: 500 mg every 8 hours for skin infections, 1 gram every 8 hours for intra-abdominal infections, or 2 grams every 8 hours for meningitis 1
• For skin infections caused by P. aeruginosa, increase to 20 mg/kg (or 1 gram if >50 kg) every 8 hours 1
• Administer as IV infusion over 15-30 minutes, or as bolus injection over 3-5 minutes 1
• Limited safety data exist for administering 40 mg/kg bolus doses; infusion is preferred for this higher dose 1

Infants <3 Months of Age:

For infants with complicated intra-abdominal infections, dose based on gestational age (GA) and postnatal age (PNA), administered as 30-minute infusions. 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 longer infusion time of 30 minutes is specifically required for this age group to ensure safety 1. There is no experience with meropenem in pediatric patients with renal impairment 1.

Neonatal Dosing from Alternative Guidelines:

The IDSA catheter-related infection guidelines provide slightly different neonatal dosing 4:

• Postnatal age 0-7 days: 20 mg/kg every 12 hours 4
• Postnatal age >7 days and 1200-2000 g: 20 mg/kg every 12 hours 4
• Postnatal age >7 days and >2000 g: 20 mg/kg every 8 hours 4

Infusion Time Considerations

The standard 15-30 minute infusion is adequate for most patients, but prolonged infusions should be considered for optimizing pharmacodynamics in specific situations. 1, 7

• Standard infusion over 15-30 minutes is recommended by the FDA label 1
• Bolus administration over 3-5 minutes is acceptable for 1 gram doses 1
• For patients with augmented renal function or infections with pathogens having MIC >1 μg/mL, consider prolonged infusions of at least 2 hours to maintain therapeutic concentrations above the MIC for a greater percentage of the dosing interval 7
• The current standard dosing regimen may be suboptimal in patients with normal or augmented renal function, particularly when treating less susceptible organisms 7

Preparation and Stability

Reconstitute vials with Sterile Water for Injection and use freshly prepared solutions whenever possible. 1

• For 500 mg vials: Add 10 mL diluent to achieve approximately 50 mg/mL concentration 1
• For 1 gram vials: Add 20 mL diluent to achieve approximately 50 mg/mL concentration 1
• Shake to dissolve and let stand until clear 1

Stability Guidelines:

• Bolus administration (reconstituted with Sterile Water): Stable for 3 hours at room temperature (up to 25°C) or 13 hours refrigerated (up to 5°C) 1
• Infusion with 0.9% Sodium Chloride (1-20 mg/mL): Stable for 1 hour at room temperature or 15 hours refrigerated 1
• Infusion with 5% Dextrose (1-20 mg/mL): Use immediately 1
• Do not freeze reconstituted solutions 1

Critical Pitfalls and Caveats

The most common error is failure to adjust dosing for renal impairment, leading to drug accumulation and potential toxicity. 1, 2

• Always calculate creatinine clearance using the Cockcroft-Gault equation when only serum creatinine is available 1
• For females, multiply the calculated value by 0.85 1
• Do not mix meropenem with other drugs; compatibility has not been established 1
• The open-ring metabolite (ICI 213,689) accumulates significantly in renal impairment, with half-life increasing from 2.3 hours to 23.6 hours, though clinical significance is unclear 2, 3
• In patients on CRRT, the wide variability in drug removal (13-53% depending on modality) creates substantial risk of underdosing; given meropenem's excellent tolerability, favor higher dosing when uncertain 5
• Nonrenal clearance accounts for approximately 20% of elimination in normal renal function but increases to 50% in severe renal impairment 3