What are the recommended antimicrobial regimens and treatment durations for Enterococcus faecium infections, including ampicillin‑susceptible strains, ampicillin‑resistant or vancomycin‑resistant (VRE) isolates, and severe infections such as bacteremia or endocarditis?

Treatment of Enterococcus faecium Infections

For ampicillin-susceptible E. faecium, use ampicillin as first-line therapy; for ampicillin-resistant strains, use vancomycin if susceptible; for vancomycin-resistant E. faecium (VRE), linezolid 600 mg IV/PO every 12 hours is the recommended treatment. 1

Ampicillin-Susceptible E. faecium

• Ampicillin is the drug of choice for ampicillin-susceptible E. faecium infections 1
• E. faecium demonstrates significantly higher resistance to penicillins compared to E. faecalis, with MICs typically ≥16 mcg/mL versus 2-4 mcg/mL for E. faecalis 2, 3
• Ampicillin MICs are usually one dilution lower than penicillin MICs 2
• For serious infections like endocarditis, use ampicillin 12 g/24 hours IV in 6 equally divided doses 2
• Duration: 4-6 weeks for native valve endocarditis (4 weeks if symptoms <3 months, 6 weeks if symptoms ≥3 months); minimum 6 weeks for prosthetic valve endocarditis 2

Combination Therapy for Severe Infections

• For endocarditis with ampicillin-susceptible strains, add gentamicin 3 mg/kg/24 hours IV/IM in 3 equally divided doses for synergy 2
• If gentamicin resistance is present but streptomycin susceptibility confirmed, use streptomycin 15 mg/kg/24 hours IV/IM in 2 equally divided doses 2
• Test all E. faecium isolates from endocarditis patients for susceptibility to both gentamicin and streptomycin 2

Ampicillin-Resistant, Vancomycin-Susceptible E. faecium

• Vancomycin 30 mg/kg/24 hours IV in 2 equally divided doses is the treatment of choice 2, 1
• Add gentamicin 3 mg/kg/24 hours IV/IM in 3 equally divided doses for serious infections like endocarditis 2
• Treatment duration: minimum 6 weeks for endocarditis 2
• E. faecium is intrinsically more resistant to penicillins than E. faecalis, making ampicillin resistance more common 2, 3

Beta-Lactamase Producing Strains

• Use ampicillin-sulbactam 12 g/24 hours IV in 4 equally divided doses for 6 weeks 2
• Add gentamicin 3 mg/kg/24 hours IV/IM in 3 equally divided doses if susceptible 2
• Beta-lactamase producing strains are unlikely to be gentamicin-susceptible; if gentamicin-resistant, use ampicillin-sulbactam alone for 6 weeks 2

Vancomycin-Resistant E. faecium (VRE)

First-Line Treatment

• Linezolid 600 mg IV/PO every 12 hours is the primary treatment for VRE 1
• Linezolid demonstrates 97-99% susceptibility against multiresistant E. faecium strains 1
• Linezolid achieved 77% cure rate in 22 courses of therapy for vancomycin-resistant enterococcal endocarditis 2

Alternative Agents for VRE

• Daptomycin 8-12 mg/kg/day IV for VRE bacteremia 1
• Higher doses (10-12 mg/kg/day) may be more effective for serious infections like endocarditis 1, 4
• Quinupristin-dalfopristin (Synercid) inhibits E. faecium growth but NOT E. faecalis (intrinsic resistance) 2, 1
• Synercid was effective in 4 of 9 patients with vancomycin-resistant E. faecium endocarditis 2

Site-Specific VRE Treatment

For intra-abdominal infections:

• Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours 1
• Duration: 5-7 days based on clinical response and source control 1

For urinary tract infections:

• Fosfomycin 3 g PO single dose or every other day for resistant strains 1
• Nitrofurantoin 100 mg PO every 6 hours for 3-7 days 1
• High-dose ampicillin 18-30 g IV daily in divided doses if susceptibility testing shows sensitivity 1
• Amoxicillin 500 mg PO/IV every 8 hours if ampicillin-susceptible 1

For bacteremia:

• Treatment duration: 10-14 days 1

For endocarditis:

• Treatment duration: at least 6 weeks 1

Resistance Patterns and Mechanisms

• E. faecium is significantly more resistant than E. faecalis to penicillin, ampicillin, piperacillin, imipenem, and ciprofloxacin 3
• Most E. faecium strains resistant to vancomycin (up to 95%) express multiple resistance to vancomycin, aminoglycosides, and penicillins 1
• Five phenotypes of vancomycin resistance exist (vanA through E), with vanA and vanB genes found primarily in E. faecium 2, 1
• VanA phenotype: high-level vancomycin resistance (MIC ≥64 mcg/mL) 2
• VanB phenotype: intermediate to high-level resistance (MIC 16-512 mcg/mL) 2
• High-level aminoglycoside resistance detected in 38% of enterococcal isolates in one U.S. study 3

Salvage Regimens for Multidrug-Resistant E. faecium

• Double β-lactam combinations (imipenem plus ampicillin OR cephalosporins plus ampicillin) demonstrate synergistic bactericidal activity by saturating different penicillin-binding protein targets 2, 5
• These combinations have been used successfully for high-level aminoglycoside-resistant strains 2
• Daptomycin plus ampicillin or ceftaroline for potential synergistic effects in severe VRE infections 1
• One case report documented successful treatment of aminoglycoside-resistant E. faecalis endocarditis with ampicillin, imipenem, and vancomycin combination 5

Critical Monitoring and Pitfalls

• Monitor for bone marrow suppression and peripheral neuropathy with prolonged linezolid use 1
• Enterococci are intrinsically resistant to cephalosporins when used as monotherapy 1
• Avoid cephalosporins as monotherapy for E. faecium infections due to natural resistance 6
• E. faecium is intrinsically resistant to amikacin, kanamycin, netilmicin, and tobramycin 2
• Ticarcillin, aztreonam, antistaphylococcal penicillins (nafcillin, methicillin), cephalosporins, cephamycins, and meropenem have limited or no activity against enterococci 2
• Imipenem has some activity against enterococci but should not be used as monotherapy 2
• Infectious diseases consultation is strongly advised for all cases of multiply-resistant VRE 1

Treatment Duration Summary

• Uncomplicated infections: 7-14 days 1
• Complicated infections/bacteremia: 10-14 days 1
• Endocarditis (native valve): 4-6 weeks (4 weeks if symptoms <3 months; 6 weeks if symptoms ≥3 months) 2
• Endocarditis (prosthetic valve): Minimum 6 weeks 2
• Intra-abdominal infections: 5-7 days based on clinical response and source control 1