What is the recommended dosing for Meropenem (generic name) in adults with normal renal function and those with impaired renal function?

Meropenem Dosing in Adults

The recommended meropenem dosing for adults with normal renal function is 1 gram every 8 hours administered as an intravenous infusion over 15-30 minutes, with dosage adjustments required based on renal function and infection type. 1, 2

Standard Dosing for Adults with Normal Renal Function

• For complicated skin and skin structure infections: 500 mg every 8 hours by intravenous infusion over 15-30 minutes 1
• For complicated skin and skin structure infections caused by Pseudomonas aeruginosa: 1 gram every 8 hours 1
• For intra-abdominal infections: 1 gram every 8 hours 1, 2
• For critically ill patients with intra-abdominal infections: 1 gram every 8 hours 3, 2
• For severe infections including bloodstream infections with carbapenem-resistant Enterobacterales: 1 gram every 8 hours by extended infusion 2

Administration Methods

• Standard administration: Intravenous infusion over 15-30 minutes 1
• Bolus administration: Intravenous bolus injection (5-20 mL) over 3-5 minutes 1
• Extended infusion: 3-hour infusion is beneficial for optimizing pharmacokinetic/pharmacodynamic properties when treating resistant organisms with higher MICs 2

Dosing in Renal Impairment

Meropenem dosing should be adjusted based on creatinine clearance as follows:

• CrCl >50 mL/min: Standard recommended dose every 8 hours 1
• CrCl 26-50 mL/min: Standard recommended dose every 12 hours 1
• CrCl 10-25 mL/min: One-half recommended dose every 12 hours 1
• CrCl <10 mL/min: One-half recommended dose every 24 hours 1

Pharmacokinetic/Pharmacodynamic Considerations

• For beta-lactams like meropenem, the key pharmacodynamic parameter for clinical efficacy is the time that plasma concentration remains above the pathogen's minimum inhibitory concentration (T>MIC) 4
• A minimum T>MIC of 60% is generally sufficient for mild to moderate infections, but optimal response in severe infections like sepsis requires T>MIC approaching 100% 4
• More frequent dosing (every 8 hours vs every 12 hours) with the same total daily dose provides better T>MIC coverage 4, 5

Special Clinical Scenarios

• For treatment of multidrug-resistant infections with meropenem MIC ≥ 8 mg/L, extended infusion of meropenem for 3 hours is recommended 2
• In critically ill patients, maintaining consistent antimicrobial levels is crucial for effective treatment 4
• Loading doses are not affected by renal function and should be administered at full dose to rapidly achieve therapeutic levels 4

Common Pitfalls to Avoid

• Assuming that less frequent dosing is always better in renal impairment ignores the importance of maintaining T>MIC 4
• Failing to consider that sepsis itself alters drug pharmacokinetics beyond what would be expected from renal impairment alone 4
• Inadequate dosing when treating resistant organisms can lead to treatment failure and promote antimicrobial resistance 6
• Delays in the administration of appropriate antimicrobial therapy have been associated with excess hospital mortality 3

Therapeutic Drug Monitoring

• Therapeutic drug monitoring (TDM) may be beneficial in critically ill patients and those with impaired renal function to ensure adequate drug levels 6
• TDM can help optimize dosing regimens, prevent treatment failure, reduce toxicity, and minimize the development of antimicrobial resistance 6

Meropenem is a carbapenem antibiotic with broad-spectrum activity against gram-positive and gram-negative bacteria, including beta-lactamase producers and Pseudomonas aeruginosa 7. Its appropriate dosing is essential to maximize clinical efficacy while minimizing the risk of adverse effects and antimicrobial resistance.