What oral antibiotics are effective for Enterococcus (Enterococcus faecalis and Enterococcus faecium, including vancomycin-resistant Enterococci) coverage?

Oral Antibiotics for Enterococcus Coverage

Linezolid 600 mg orally every 12 hours is the primary oral antibiotic for Enterococcus coverage, including vancomycin-resistant enterococci (VRE), with proven efficacy against both E. faecalis and E. faecium. 1, 2

First-Line Oral Options by Species and Resistance Pattern

For Ampicillin-Susceptible Enterococci

• Amoxicillin 500 mg orally every 8 hours is the preferred oral agent when enterococci are ampicillin-susceptible and patients can tolerate penicillins 1, 3
• Ampicillin-susceptible strains represent approximately 97% of E. faecalis infections but are less common in E. faecium 4, 5

For Vancomycin-Resistant Enterococci (VRE)

• Linezolid 600 mg orally every 12 hours is the guideline-recommended oral agent for VRE, with 92-97% susceptibility rates and clinical cure rates of 67-92% 1, 5, 2, 6
• Linezolid demonstrates bacteriostatic activity against both E. faecalis (MIC₉₀ = 2-4 μg/ml) and E. faecium (MIC₉₀ = 2-4 μg/ml) 6, 7
• Treatment duration ranges from 7-14 days for uncomplicated infections to 14-28 days for complicated infections including bacteremia 2

Site-Specific Oral Options

Uncomplicated Urinary Tract Infections Due to VRE

Multiple oral options exist with strong guideline support:

• Fosfomycin 3 g orally as a single dose is recommended for uncomplicated VRE cystitis 1, 5
• Nitrofurantoin 100 mg orally every 6 hours for 3-7 days is an effective alternative 1, 5
• High-dose amoxicillin 500 mg orally every 8 hours can be used if ampicillin-susceptible 1, 5

Complicated Infections

• Linezolid remains the only reliable oral option for complicated VRE infections outside the urinary tract 1, 4, 5
• For skin and soft tissue infections, linezolid 600 mg orally every 12 hours for 10-14 days is recommended 2

Critical Resistance Considerations

E. faecium vs. E. faecalis

• E. faecium is significantly more likely to be multidrug-resistant compared to E. faecalis 5, 3
• Approximately 95% of vancomycin-resistant E. faecium strains express multiple resistance to vancomycin, aminoglycosides, and penicillins 5

Linezolid Resistance

• Linezolid resistance in enterococci is emerging but remains uncommon, with resistance rates of 1-3% 6, 8
• Tedizolid is NOT a reliable alternative for linezolid-resistant VRE, as most isolates with 23S rDNA mutations remain above the susceptibility breakpoint 8

Important Clinical Caveats

Agents to Avoid

• Cephalosporins have NO activity against enterococci when used as monotherapy due to intrinsic resistance 4, 5
• Fluoroquinolones are NOT recommended for enterococcal infections due to poor activity 4
• Quinupristin-dalfopristin is inactive against E. faecalis and should only be considered for E. faecium (not available orally) 5, 6

Linezolid Monitoring

• Monitor for thrombocytopenia with courses exceeding 14-21 days, as this is the most significant dose-limiting toxicity 6, 7
• Gastrointestinal disturbances (nausea, vomiting, diarrhea), headache, and taste alteration are common but generally manageable 6, 7
• Monitor for peripheral neuropathy and optic neuropathy with prolonged use beyond 28 days 5

Bioavailability Advantage

• Linezolid has excellent oral bioavailability (100%), allowing seamless transition from IV to oral therapy without dose adjustment 2, 7
• Patients can be switched from IV to oral linezolid at the same dose (600 mg every 12 hours) when clinically appropriate 2

Treatment Duration by Infection Type

• Uncomplicated UTI: 3-7 days with nitrofurantoin or single-dose fosfomycin 5
• Uncomplicated skin/soft tissue: 10-14 days with linezolid 2
• Complicated infections or bacteremia: 14-28 days with linezolid 1, 2
• Endocarditis: minimum 6 weeks (typically requires IV therapy initially) 5