What is an appropriate antibiotic regimen for a patient suspected of having an infection caused by Enterococcus faecium, including those with vancomycin-resistant strains?

Antibiotic Coverage for Enterococcus faecium

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

Treatment Algorithm Based on Susceptibility Pattern

Ampicillin-Susceptible E. faecium

• Ampicillin is the drug of choice when susceptibility testing confirms sensitivity 1
• This represents the minority of E. faecium isolates, as E. faecium is more likely to be multidrug-resistant compared to E. faecalis 1

Vancomycin-Susceptible, Ampicillin-Resistant E. faecium

• Vancomycin 30 mg/kg per 24 hours IV in 2 equally divided doses for 6 weeks (for endocarditis) 2
• Adjust vancomycin to achieve serum trough concentration of 10-20 μg/mL 2
• Add gentamicin 3 mg/kg per 24 hours IV or IM in 3 equally divided doses for synergistic activity in serious infections like endocarditis 2
• For patients unable to tolerate β-lactams with susceptible strains, vancomycin plus gentamicin for 6 weeks is recommended (Class IIa; Level of Evidence B) 2

Vancomycin-Resistant E. faecium (VRE)

First-Line for VRE:

• Linezolid 600 mg IV or PO every 12 hours for at least 6 weeks for serious infections like endocarditis 1, 3
• Linezolid has 97-99% susceptibility against multidrug-resistant enterococci including VRE 2
• Linezolid is bacteriostatic against enterococci 2, 4
• FDA-approved for VRE infections with cure rates of 67% (39/58) in high-dose arm versus 52% (24/46) in low-dose arm 3

Alternative for VRE:

• Daptomycin 10-12 mg/kg/day IV is recommended as an alternative, particularly for bacteremia and serious infections requiring bactericidal activity 1, 5
• Standard doses of 6-8 mg/kg/day are insufficient; high doses (10-12 mg/kg/day) demonstrate sustained bactericidal activity 2, 5
• Daptomycin monotherapy has variable success rates and risk of resistance emergence during treatment 2

Combination Therapy for Severe VRE Infections:

• Daptomycin plus ampicillin or daptomycin plus ceftaroline shows the greatest synergistic activity in vitro and should be considered for complex infections 2, 6
• Ampicillin reduces the net positive charge of the bacterial surface by releasing lipoteichoic acid, enhancing daptomycin binding 6
• This combination is particularly important for strains with daptomycin MICs in the higher susceptible range (<4 μg/mL) 2
• Other less active combinations include daptomycin with gentamicin, rifampin, or tigecycline 2

Third-Line Option:

• Quinupristin-dalfopristin 7.5 mg/kg IV every 8 hours has activity against E. faecium (but NOT E. faecalis) with 70.5% clinical response rate 1, 4
• Limited by severe myalgia/arthralgia as treatment-limiting adverse effect 4
• Species identification is mandatory before using this agent 1

Site-Specific Treatment Considerations

Urinary Tract Infections (Uncomplicated)

• Fosfomycin 3 g PO single dose 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 susceptible 1
• Amoxicillin 500 mg PO/IV every 8 hours if ampicillin-susceptible 1

Intra-Abdominal Infections

• Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours when standard agents have failed 1
• Treatment duration of 5-7 days based on clinical response and source control 1
• Tigecycline has minimal published clinical data for VRE but shows in vitro activity 2

Endocarditis

• Linezolid for at least 6 weeks with cure rate of 77% in VRE endocarditis cases 1
• High-dose daptomycin 10-12 mg/kg/day may be more effective for endocarditis 1
• Consider combination therapy with daptomycin plus ampicillin or ceftaroline 2
• Infectious disease, cardiology, and cardiovascular surgery consultation is mandatory 2

Bacteremia and Complicated Infections

• Linezolid 600 mg IV/PO every 12 hours for 10-14 days 1
• Daptomycin 10-12 mg/kg/day IV as alternative 1
• Consider combination therapy for persistent bacteremia despite source control 6

Critical Monitoring and Pitfalls

Linezolid Monitoring

• Watch for bone marrow suppression (thrombocytopenia typically after >14-21 days of therapy) 2, 1, 3
• Monitor for peripheral and optic neuropathy with prolonged use 2, 1
• Check for drug interactions, particularly with serotonergic agents 1

Daptomycin Monitoring

• Monitor creatine phosphokinase (CPK) levels for myopathy 2
• Watch for intractable muscle pain as treatment-limiting adverse effect 2
• Resistance can emerge during monotherapy, particularly with lower doses 2, 5
• Daptomycin is NOT FDA-approved for endocarditis 2

Common Pitfalls to Avoid

• Do not use cephalosporins as monotherapy - enterococci are intrinsically resistant 2, 1
• Do not use daptomycin monotherapy for severe enterococcal infections - consider combination therapy 2, 1
• Do not use quinupristin-dalfopristin for E. faecalis - it is only active against E. faecium 1, 4
• Do not use standard daptomycin doses (6 mg/kg/day) for serious VRE infections - use 10-12 mg/kg/day 2, 1, 5
• Obtain susceptibility testing including MIC determination for penicillin/ampicillin, vancomycin, and high-level gentamicin resistance 2, 1

Treatment Duration

• Uncomplicated infections: 7-14 days 1
• Bacteremia: 10-14 days 1
• Endocarditis: at least 6 weeks 2, 1
• Complicated infections: duration based on clinical response 1

Special Populations

Pediatric Patients

• Linezolid 10 mg/kg IV or oral every 8 hours for children birth through 11 years 3
• Neonates <7 days should start with 10 mg/kg every 12 hours, then advance to every 8 hours by day 7 of life 3
• Adolescents ≥12 years receive adult dosing of 600 mg every 12 hours 3
• Infectious disease consultation is standard of care for pediatric enterococcal infections 2