Meropenem Recommendations for Enterobacterales Infections
For susceptible Enterobacterales infections, use meropenem 1 gram IV every 8 hours for most serious infections, with extended 3-hour infusions reserved for carbapenem-resistant strains or when MIC ≥8 mg/L. 1
Standard Dosing for Susceptible Enterobacterales
- Complicated intra-abdominal infections: 1 gram IV every 8 hours, infused over 15-30 minutes 2
- Bloodstream infections: 1 gram IV every 8 hours for 7-14 days depending on source control 1
- Complicated urinary tract infections: 1 gram IV every 8 hours for 5-7 days 1
- Skin and soft tissue infections: 500 mg IV every 8 hours (increase to 1 gram every 8 hours for P. aeruginosa) 2
The FDA-approved dosing allows for bolus administration (over 3-5 minutes) for 1 gram doses, though infusion over 15-30 minutes is standard 2. Meropenem demonstrates excellent penetration into peritoneal fluid, achieving similar concentrations to plasma within 1 hour 3.
Carbapenem-Resistant Enterobacterales (CRE)
For CRE infections, meropenem should NOT be used as monotherapy but may be considered in combination regimens with extended infusion. 4
Combination Therapy Approach
Preferred regimens for CRE bloodstream infections: 4
- Ceftazidime-avibactam 2.5 g IV every 8 hours (first-line)
- Meropenem-vaborbactam 4 g IV every 8 hours
- Polymyxin-based combinations: Colistin + meropenem 1 g IV every 8 hours by extended infusion (3 hours)
Extended infusion is mandatory: When using meropenem for CRE, administer 1 gram IV every 8 hours as a 3-hour infusion 4, 1. For isolates with MIC ≥8 mg/L, this extended infusion is critical to achieve adequate time above MIC 1.
High-dose regimens: For KPC-producing strains with MIC ≥16 mg/L, consider 2 grams IV every 8 hours by 3-hour extended infusion as part of combination therapy 1
CRE Treatment Duration
- Bloodstream infections: 7-14 days 4
- Complicated urinary tract infections: 5-7 days 4
- Complicated intra-abdominal infections: 5-7 days 4
ESBL-Producing Enterobacterales
Meropenem remains highly effective for ESBL-producers and is preferred over other beta-lactams. 5
- Standard dosing applies: 1 gram IV every 8 hours for serious infections 4
- Alternative for non-critically ill patients: Ertapenem 1 gram IV every 24 hours may be used for community-acquired ESBL infections in stable patients 4
- Critically ill or septic shock patients: Use meropenem 1 gram every 6 hours by extended infusion or continuous infusion 4
Renal Dose Adjustments
Dosing must be reduced for creatinine clearance ≤50 mL/min: 2
- CrCl 26-50 mL/min: Recommended dose every 12 hours
- CrCl 10-25 mL/min: Half the recommended dose every 12 hours
- CrCl <10 mL/min: Half the recommended dose every 24 hours
Critical Dosing Considerations
Extended infusion strategy: 1
- Target 70% time above MIC for optimal bactericidal activity
- For critically ill patients or deep-seated infections, consider continuous infusion
- Meropenem stability during continuous infusion requires monitoring
No loading dose required: Unlike colistin or tigecycline, meropenem does not require a loading dose for standard administration 1
Common Pitfalls to Avoid
- Do not use standard dosing for CRE: Extended infusion is mandatory, not optional 4, 1
- Avoid monotherapy for CRE: Combination therapy based on susceptibility testing is essential 4
- Do not assume carbapenem efficacy: Always obtain MIC values for CRE; meropenem may still be effective at MIC ≤8 mg/L with optimized dosing 6
- Inadequate duration: Ensure source control is adequate before shortening treatment courses 4
- Renal function monitoring: Failure to adjust for renal impairment leads to toxicity or inadequate dosing 2
Carbapenem-Sparing Alternatives
For non-CRE, carbapenem-susceptible Enterobacterales in stable patients, consider: 4
- Piperacillin-tazobactam 4.5 g IV every 6 hours
- Ceftriaxone 2 g IV every 24 hours + metronidazole (for intra-abdominal infections)
However, meropenem provides superior coverage and is preferred for critically ill patients or those with high risk of ESBL-producers 4.