From the Guidelines
No, Merrem (meropenem) does not adequately cover penicillin-sensitive Enterococcus faecalis. While meropenem is a broad-spectrum carbapenem antibiotic effective against many gram-positive and gram-negative bacteria, it has poor activity against enterococci, including penicillin-sensitive E. faecalis. For treating infections caused by penicillin-sensitive E. faecalis, more appropriate options include:
- ampicillin (2g IV every 4-6 hours)
- penicillin G (3-4 million units IV every 4 hours),
- or combination therapy with ampicillin plus gentamicin for synergy in serious infections like endocarditis, as recommended by the 2015 ESC guidelines for the management of infective endocarditis 1. The reason for meropenem's poor activity against enterococci relates to its binding affinity for penicillin-binding proteins in enterococci, which differs from its activity against other gram-positive organisms. When treating suspected or confirmed E. faecalis infections, it's essential to select antibiotics with known activity against this organism rather than relying on carbapenems like meropenem. Recent guidelines, such as the 2024 WHO's essential medicines and aware recommendations, prioritize ampicillin for enterococcal coverage in certain regimens 1, further supporting the choice of ampicillin over meropenem for penicillin-sensitive E. faecalis. In contrast, meropenem is recommended for other types of infections, such as hospital-acquired infections in critically ill patients, as seen in the 2017 WSES guidelines for management of intra-abdominal infections 1. However, for penicillin-sensitive E. faecalis, the most appropriate choice is an antibiotic with known efficacy against this organism. Ampicillin or penicillin G, potentially combined with gentamicin, are the preferred treatments for infections caused by penicillin-sensitive E. faecalis, prioritizing morbidity, mortality, and quality of life outcomes.
From the FDA Drug Label
Table 8: Clinical Efficacy Rates by Pathogen for Clinically Evaluable Population MICROORGANISMS1Meropenem for Injection n 2/N 3(%) 4Imipenem-cilastatin n 2/N 3(%) 4 Gram-positive aerobes Staphylococcus aureus,methicillin susceptible 82/88 (93)84/100 (84) Streptococcus pyogenes(Group A) 26/29 (90)28/32 (88) Streptococcus agalactiae(Group B) 12/17 (71)16/19 (84) Enterococcus faecalis9/12 (75)14/20 (70) Viridans group streptococci11/12 (92)5/6 (83)
The drug label shows that meropenem has a 75% clinical efficacy rate against Enterococcus faecalis.
- Key points:
- Meropenem has been tested against Enterococcus faecalis.
- The clinical efficacy rate is 75%.
- Clinical decision: Merrem (meropenem) may be effective against penicillin-sensitive Enterococcus faecalis, but the efficacy rate is not 100%. 2
From the Research
Merrem Coverage for Penicillin-Sensitive Enterococcus faecalis
- Meropenem (Merrem) is a broad-spectrum antibacterial agent with activity against Gram-positive and Gram-negative pathogens, including Enterobacteriaceae 3.
- However, the study from 2007 states that carbapenems, including meropenem, lack activity against Enterococcus faecium, but it does not explicitly mention Enterococcus faecalis 4.
- A study from 2022 found that meropenem plus ceftaroline demonstrated significant kill against penicillin-susceptible E. faecalis strains, with no regrowth or MIC increases occurring 5.
- Another study from 2023 found that meropenem plus ceftriaxone or ertapenem plus ceftriaxone demonstrated synergistic activity against E. faecalis strains, including those with reduced penicillin susceptibility 6.
- It is worth noting that the standard of care for serious E. faecalis infections is ampicillin plus ceftriaxone, but meropenem-based combination therapy may provide an alternative option 5, 7.
Key Findings
- Meropenem has broad-spectrum activity, but its effectiveness against E. faecalis is not well-established 3, 4.
- Combination therapy with meropenem and ceftaroline or ceftriaxone may be effective against E. faecalis 5, 6.
- Further studies are needed to determine the clinical efficacy of meropenem-based combination therapy for E. faecalis infections 5, 7.