Meropenem Does NOT Cover Enterococcus Bacteremia
Meropenem is ineffective against enterococcal bacteremia and should never be used as monotherapy for this infection. Enterococci possess intrinsic resistance to all carbapenems, including meropenem, due to their low-affinity penicillin-binding proteins 1, 2.
Mechanism of Intrinsic Resistance
- Enterococci demonstrate limited or no susceptibility to all carbapenems through intrinsic resistance mechanisms involving altered penicillin-binding proteins that prevent effective carbapenem binding 1, 2
- The FDA-approved labeling for meropenem specifically lists Enterococcus faecalis (vancomycin-susceptible isolates only) as a covered pathogen only for complicated skin and skin structure infections, not for bacteremia 3
- Multiple guideline societies, including the American Heart Association and American College of Cardiology, explicitly state that carbapenems lack activity against Enterococcus species 1
Appropriate Treatment Options for Enterococcal Bacteremia
For Ampicillin-Susceptible E. faecalis:
- Ampicillin 300 mg/kg/day IV in 4-6 divided doses is the drug of choice, often combined with gentamicin 3 mg/kg/day for synergistic effect if aminoglycoside-susceptible 2, 4
- Alternative regimens include ampicillin plus ceftriaxone for patients where aminoglycosides are contraindicated 4
For Vancomycin-Resistant Enterococci (VRE):
- Linezolid 600 mg IV every 12 hours is recommended as first-line therapy for VRE bacteremia 4
- Daptomycin 8-12 mg/kg IV daily is an alternative option based on susceptibility results 4
- Treatment duration is typically 10-14 days for uncomplicated bacteremia 4
For Ampicillin-Resistant but Vancomycin-Susceptible Enterococci:
- Vancomycin plus an aminoglycoside (if susceptible) is the recommended treatment 2
Critical Clinical Pitfalls
- Never rely on meropenem for enterococcal coverage in polymicrobial infections where enterococci are suspected or confirmed; add specific anti-enterococcal agents such as ampicillin, piperacillin-tazobactam, or vancomycin 2
- Empiric anti-enterococcal therapy should be added for healthcare-associated infections, postoperative infections, and patients with prior cephalosporin exposure 2
- For complicated intra-abdominal or skin/soft tissue infections where both gram-negative bacteria and enterococci are concerns, combination therapy or alternative agents with broader spectrum are required 1, 2
- Transesophageal echocardiography should be performed if enterococcal bacteremia persists >72 hours despite appropriate therapy, as this suggests possible endocarditis 4
Special Consideration: Experimental Combination Therapy
- Recent in vitro research suggests that meropenem plus ceftaroline may demonstrate activity against E. faecalis through synergistic mechanisms, showing comparable activity to ampicillin plus ceftriaxone in pharmacodynamic models 5
- However, this combination remains investigational and is not currently recommended for clinical use pending further clinical efficacy studies 5
- This finding does not change the current standard that meropenem monotherapy is completely ineffective against enterococcal infections 5