Meropenem Initiation: Loading and Maintenance Dosing
Meropenem does not require a loading dose for standard administration in adults with normal renal function; initiate with maintenance dosing only. 1
Standard Maintenance Dosing for Adults with Normal Renal Function
The FDA-approved maintenance regimens are 2:
- 500 mg IV every 8 hours for complicated skin and skin structure infections (cSSSI)
- 1 gram IV every 8 hours for complicated intra-abdominal infections
- 1 gram IV every 8 hours when treating cSSSI caused by Pseudomonas aeruginosa
Administration Methods
- Standard infusion: Administer over 15-30 minutes 2
- Bolus injection: 1 gram doses may be given as IV bolus (5-20 mL) over 3-5 minutes 2
- Extended infusion: For critically ill patients or resistant organisms (MIC ≥8 mg/L), administer over 3 hours 3, 1
Optimized Dosing for Critically Ill Patients
Higher doses should be used at treatment onset in ICU patients with preserved renal function due to altered pharmacokinetics. 3
- 2 grams IV every 8 hours is recommended for severe infections in ICU patients 3, 1
- Extended infusion over 3 hours optimizes pharmacodynamic properties when treating resistant organisms 3, 1
- ICU patients have increased clearance and altered volume of distribution, making standard doses potentially inadequate 3
Why No Loading Dose is Required
Meropenem's pharmacokinetic profile does not necessitate a loading dose, unlike other antibiotics such as colistin, tigecycline, or vancomycin which do require loading. 1
- Peak concentrations (Cmax) of approximately 30 mg/L are achieved rapidly after standard dosing 4
- The elimination half-life is approximately 1 hour in patients with normal renal function 4
- Optimization is achieved through extended infusion duration rather than loading doses 1
Dose Adjustments for Renal Impairment
Dosage reduction is mandatory in patients with creatinine clearance ≤50 mL/min. 2
| Creatinine Clearance (mL/min) | Dose | Interval |
|---|---|---|
| >50 | Standard dose (500 mg or 1 g) | Every 8 hours |
| 26-50 | Standard dose | Every 12 hours |
| 10-25 | Half standard dose | Every 12 hours |
| <10 | Half standard dose | Every 24 hours |
Therapeutic Drug Monitoring Considerations
TDM is recommended in ICU patients with clinical signs of toxicity or expected pharmacokinetic variability. 3
- Target: Maintain plasma concentration above the MIC of the suspected pathogen throughout the dosing interval 3
- Neurological toxicity risk: Trough concentrations >64 mg/L are associated with seizures and neurological deterioration 3
- TDM is particularly important in patients on renal replacement therapy 3
Critical Pitfalls to Avoid
- Underdosing in ICU patients: Standard doses may be inadequate due to increased clearance in critically ill patients with preserved renal function 3
- Continuous infusion stability: Meropenem has limited stability at room temperature (6-12 hours), requiring preparation of new infusion bags every 6 hours 3
- Failure to extend infusion for resistant organisms: When MIC ≥8 mg/L, extended 3-hour infusion is essential to achieve adequate time above MIC 3, 1
- Inappropriate dose reduction in renal impairment: While dose adjustment is necessary, maintaining adequate individual doses (not below 1 gram when indicated) is important for efficacy 5
Pediatric Dosing (≥3 Months of Age)
For pediatric patients with normal renal function 2:
- 10 mg/kg every 8 hours (max 500 mg) for cSSSI
- 20 mg/kg every 8 hours (max 1 gram) for complicated intra-abdominal infections
- 20 mg/kg every 8 hours (max 1 gram) for cSSSI caused by P. aeruginosa
- 40 mg/kg every 8 hours (max 2 grams) for meningitis