What is the recommended use and dosage of Meropenem for treating bacterial infections?

Meropenem: Recommended Use and Dosage for Bacterial Infections

Meropenem is a broad-spectrum carbapenem antibiotic recommended at a standard dose of 1 gram every 8 hours intravenously for most severe bacterial infections, with dosage adjustments required for renal impairment and specific infection types. 1

General Characteristics and Spectrum

• Meropenem is a carbapenem antibiotic with ultra-broad spectrum activity against Gram-positive and Gram-negative aerobes and anaerobes, including many multi-drug resistant organisms 2
• Unlike imipenem, meropenem does not require co-administration with cilastatin as it is relatively stable to human dehydropeptidase-I (DHP-I) 2
• Meropenem is more active against Enterobacteriaceae and Pseudomonas aeruginosa compared to imipenem, but slightly less active against some Gram-positive cocci 2

FDA-Approved Indications

• Complicated skin and skin structure infections in adults and pediatric patients ≥3 months of age 1
• Complicated intra-abdominal infections (appendicitis and peritonitis) in adults and pediatric patients 1
• Bacterial meningitis in pediatric patients ≥3 months of age 1

Standard Dosing for Adults

• Skin and skin structure infections: 500 mg IV every 8 hours 1
  • When treating infections caused by Pseudomonas aeruginosa, increase to 1 gram every 8 hours 1
• Intra-abdominal infections: 1 gram IV every 8 hours 1
• Administration: Intravenous infusion over 15-30 minutes or as IV bolus injection over 3-5 minutes 1

Dosing in Special Populations

Adults with Renal Impairment

• 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: Half recommended dose every 12 hours 1
• CrCl <10 mL/min: Half recommended dose every 24 hours 1

Pediatric Patients

• ≥3 months of age:
  • Skin/soft tissue infections: 10 mg/kg every 8 hours (max 500 mg) 1
  • Intra-abdominal infections: 20 mg/kg every 8 hours (max 1 gram) 1
  • Meningitis: 40 mg/kg every 8 hours (max 2 grams) 1
• <3 months of age: Dosing based on gestational and postnatal age for intra-abdominal infections 1

Use in Specific Infections

Carbapenem-Resistant Enterobacterales (CRE)

• For bloodstream infections: Meropenem 1 gram IV every 8 hours by extended infusion (3 hours) may be used in combination therapy 3
• For complicated intra-abdominal infections: Meropenem 1 gram IV every 8 hours by extended infusion may be used in combination with other agents 3
• Extended-infusion of meropenem for 3 hours is suggested if meropenem MIC is ≥8 mg/L 3

Multidrug-Resistant Organisms

• For severe infections with limited treatment options, meropenem may be used in combination with polymyxins or tigecycline 3
• Meropenem/vaborbactam 4 grams IV every 8 hours is recommended for CRE infections when susceptible 3

Complicated Intra-abdominal Infections

• Meropenem 1 gram every 8 hours IV is an effective single-drug regimen for complicated intra-abdominal infections 3
• Treatment duration should typically be 5-7 days, individualized based on infection site, source control, and clinical response 3

Pharmacokinetic/Pharmacodynamic Considerations

• The main parameter associated with therapeutic success is the percentage of time that drug levels remain above the minimum inhibitory concentration (MIC) 4
• Critically ill patients and those with impaired renal function are most suitable for therapeutic drug monitoring (TDM) to guide therapy 4
• In patients with septic shock and continuous renal replacement therapy, residual diuresis affects meropenem clearance and should be considered when determining dosing 5
• For difficult-to-treat pathogens with MICs close to resistance breakpoints (2-4 mg/L), extended infusions may be more effective than bolus dosing 5

Common Pitfalls and Caveats

• Inadequate dosing can lead to therapeutic failure and increased risk of antimicrobial resistance 4
• Standard dosing may be insufficient in critically ill patients due to altered pharmacokinetics 4, 5
• For Pseudomonas aeruginosa infections, higher doses (1 gram every 8 hours) are required even for skin and soft tissue infections 1
• Meropenem is not effective against methicillin-resistant staphylococci and Enterococcus faecium 6
• Prolonged or continuous infusions should be considered for critically ill patients with healthcare-associated infections to optimize pharmacodynamic targets 3