Meropenem is NOT Effective Against E. faecalis
Meropenem should not be used as monotherapy for E. faecalis infections because enterococci have intrinsic resistance to carbapenems, including meropenem, due to low-affinity penicillin-binding proteins. 1
Intrinsic Resistance Mechanism
- Enterococci demonstrate limited or no susceptibility to all carbapenems, including meropenem, due to their intrinsic resistance mechanisms 1
- While the FDA label lists E. faecalis (vancomycin-susceptible isolates only) as a susceptible organism 2, this is misleading in clinical practice
- Carbapenems lack clinically reliable activity against Enterococcus species 1, 3
- Among common human pathogens, Enterococcus faecium is uniformly resistant to meropenem, and E. faecalis shows only marginal susceptibility at best 4
Recommended Treatment Options for E. faecalis
First-line therapy:
- Ampicillin remains the drug of choice for E. faecalis infections when the organism is susceptible 5, 6
- Ampicillin 300 mg/kg/day IV in 4-6 equally divided doses (or 2g IV every 4 hours for serious infections like endocarditis) 5, 6
- For serious infections like endocarditis, combine ampicillin with gentamicin 3 mg/kg/day for synergistic effect (if aminoglycoside-susceptible) 5, 6
Alternative regimens:
- Ampicillin plus ceftriaxone (4g/day IV in 2 doses for 6 weeks) is active against E. faecalis strains with and without high-level aminoglycoside resistance 5, 6
- Vancomycin 30 mg/kg/day IV in 2 doses plus gentamicin for vancomycin-susceptible, ampicillin-resistant strains 5, 6
- Daptomycin 8-12 mg/kg/day for vancomycin-resistant E. faecalis 6
- Linezolid 600 mg IV/PO every 12 hours for multidrug-resistant strains 5, 6
Critical Clinical Pitfalls
When treating intra-abdominal or skin/soft tissue infections:
- If meropenem is used empirically for polymicrobial infections, you must add specific anti-enterococcal coverage (ampicillin, piperacillin-tazobactam, or vancomycin) when enterococci are suspected or confirmed 5
- Empiric anti-enterococcal therapy is recommended for healthcare-associated infections, postoperative infections, and patients with prior cephalosporin exposure 5
- Piperacillin-tazobactam can be used as it provides both broad gram-negative coverage and anti-enterococcal activity 5, 6
Emerging Research Context
- Recent in vitro studies suggest meropenem plus ceftaroline may have activity against E. faecalis using optimized dosing strategies 7, 8
- However, these are experimental findings from pharmacodynamic models only and should not guide current clinical practice 7
- No clinical trials support the use of meropenem-based regimens for E. faecalis infections in humans 7
Bottom Line for Clinical Practice
Avoid meropenem monotherapy when E. faecalis is documented or strongly suspected. 1 If using meropenem for other indications (e.g., carbapenem-resistant gram-negatives), always add ampicillin, piperacillin-tazobactam, or vancomycin to ensure adequate enterococcal coverage. 5, 6