From the Guidelines
Enterococcus infections are typically treated with a combination of antibiotics due to their intrinsic resistance to many antimicrobial agents, with the most recent guidelines recommending linezolid (600mg IV/oral twice daily), daptomycin (8-12mg/kg IV once daily), or tigecycline (100mg IV loading dose, then 50mg IV twice daily) for vancomycin-resistant enterococci (VRE) 1.
Treatment Options
- For uncomplicated Enterococcus faecalis infections, ampicillin (2g IV every 4-6 hours) or penicillin G (3-4 million units IV every 4 hours) is the preferred treatment.
- For more serious infections like endocarditis or bacteremia, combination therapy with ampicillin plus gentamicin (1mg/kg IV every 8 hours) is recommended for synergistic killing.
- For patients with penicillin allergies, vancomycin (15-20mg/kg IV every 8-12 hours) is the alternative.
- Enterococcus faecium is often more resistant, frequently requiring vancomycin.
- For vancomycin-resistant enterococci (VRE), linezolid, daptomycin, or tigecycline may be used.
Treatment Duration
- Treatment duration typically ranges from 7-14 days for uncomplicated infections to 4-6 weeks for endocarditis.
- The duration of treatment should be individualized according to infection sites, source control, the underlying comorbidities, and the initial response to therapy 1.
Resistance Mechanisms
- Enterococci are challenging to treat because they possess intrinsic resistance mechanisms including low-affinity penicillin-binding proteins, aminoglycoside-modifying enzymes, and efflux pumps, necessitating higher doses and often combination therapy for effective treatment.
- The emergence of high-level vancomycin, ampicillin, and aminoglycoside resistance in some enterococcal species has further complicated treatment choices 1.
From the FDA Drug Label
Daptomycin has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections [see Indications and Usage (1)] Gram-Positive Bacteria Enterococcus faecalis (vancomycin-susceptible isolates only) Staphylococcus aureus (including methicillin-resistant isolates) Streptococcus agalactiae Streptococcus dysgalactiae subsp. equisimilis Streptococcus pyogenes The following in vitro data are available, but their clinical significance is unknown At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for daptomycin against isolates of similar genus or organism group. However, the efficacy of daptomycin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials Gram-Positive Bacteria Corynebacterium jeikeium Enterococcus faecalis (vancomycin-resistant isolates) Enterococcus faecium (including vancomycin-resistant isolates) Staphylococcus epidermidis (including methicillin-resistant isolates) Staphylococcus haemolyticus
Antibiotics for Enterococcus
- Daptomycin: active against vancomycin-susceptible Enterococcus faecalis and has in vitro activity against vancomycin-resistant Enterococcus faecalis and Enterococcus faecium, but its efficacy in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials 2.
- Linezolid: has been studied for the treatment of vancomycin-resistant enterococcal infections and has shown cure rates of 67% for any site of infection and 59% for bacteremia of unknown origin 3.
From the Research
Enterococcus Antibiotics
- Enterococcus species are a significant cause of nosocomial infections, and their resistance to antimicrobials is a growing concern 4.
- Vancomycin-resistant Enterococcus faecium (VRE) strains are particularly problematic, with high rates of resistance to traditional antibiotics such as ampicillin and vancomycin 4, 5.
- Newer antimicrobial agents, including daptomycin, linezolid, quinupristin-dalfopristin, and tigecycline, have been introduced to combat VRE infections, but resistance to these agents is also emerging 4, 5.
- Combination therapies, such as β-lactams and fosfomycin, have shown promise in treating VRE infections, but more research is needed to determine their effectiveness 4, 6.
Treatment Options
- Daptomycin and linezolid are commonly used to treat vancomycin-resistant enterococcal bacteremia, but the optimal treatment is still unclear 6.
- A review of eight studies comparing linezolid and daptomycin found no significant difference in outcomes, but highlighted the need for well-designed prospective studies to determine the best treatment approach 6.
- Alternative dual-beta-lactam combinations, such as meropenem plus ceftriaxone or ertapenem plus ceftriaxone, have shown synergistic activity against Enterococcus faecalis strains with elevated penicillin MICs 7.
Resistance Mechanisms
- The emergence of resistance to antimicrobials is a complex issue, involving multiple mechanisms and factors, including the transfer of resistance determinants to other pathogens 8.
- Penicillin-binding proteins (PBPs) play a crucial role in the development of resistance to beta-lactam antibiotics, and understanding their structure and function is essential for developing effective treatment strategies 7.
- The expression of PBPs, such as PBP2B and PBP4, can contribute to reduced penicillin susceptibility, but the relationship between PBP expression and resistance is not fully understood 7.