What is the recommended treatment for a patient with an Enterococcus faecalis infection, considering potential antibiotic resistance?

Treatment of Enterococcus faecalis Infections

Ampicillin 2 g IV every 4-6 hours is the gold standard first-line treatment for susceptible Enterococcus faecalis infections, as most strains retain ampicillin susceptibility. 1

Initial Antibiotic Selection

For Susceptible E. faecalis

• Ampicillin 2 g IV every 4-6 hours is the preferred agent, as approximately 97% of E. faecalis strains remain susceptible to β-lactams 2, 1
• Amoxicillin may be preferred over ampicillin due to lower minimum inhibitory concentrations (MIC) 1
• Only 3% of E. faecalis strains are multidrug-resistant, and many vancomycin-resistant E. faecalis remain penicillin-susceptible 1

When Synergy is Required (Serious Infections)

For infections requiring bactericidal activity such as endocarditis or severe bacteremia:

• Combine ampicillin with gentamicin to achieve synergistic killing 2, 1
• This combination is essential because enterococci are relatively impermeable to aminoglycosides alone, and cell wall-active agents like ampicillin increase permeability to allow bactericidal concentrations 2
• Critical caveat: Test for high-level aminoglycoside resistance (≥500 μg/mL gentamicin or ≥1000 μg/mL streptomycin) before using combination therapy, as synergy will not occur if high-level resistance is present 2

For Vancomycin-Resistant E. faecalis (VRE)

• Linezolid 600 mg IV or PO every 12 hours is the recommended first-line agent 2, 1
• High-dose daptomycin 8-12 mg/kg/day IV, or in combination with β-lactams (penicillins, cephalosporins, or carbapenems), is an alternative for VRE bacteremia 2, 1
• Many vancomycin-resistant E. faecalis remain ampicillin-susceptible, so always check susceptibilities before defaulting to linezolid 1

Site-Specific Treatment Durations

Endocarditis

• Native valve with symptoms <3 months: 4 weeks of ampicillin plus gentamicin 2
• Native valve with symptoms >3 months: 6 weeks of therapy 2
• Prosthetic valve or prosthetic material: Minimum 6 weeks of therapy 2, 1
• Gentamicin is recommended for patients with creatinine clearance >50 mL/min 2
• For patients with creatinine clearance <50 mL/min or who develop renal insufficiency during gentamicin therapy, consider alternative regimens 2

Intra-abdominal Infections

• Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours for VRE intra-abdominal infections 2
• Duration based on clinical response and source control 2
• For hospital-acquired intra-abdominal infections with VRE, linezolid (mono-microbial) or tigecycline (polymicrobial) is appropriate 2

Urinary Tract Infections

• Uncomplicated UTI: Single dose of fosfomycin 3 g PO for VRE 2
• Alternative for uncomplicated UTI: Nitrofurantoin 100 mg PO every 6 hours for VRE 2
• Complicated UTI or pyelonephritis: Levofloxacin is FDA-approved for E. faecalis in complicated UTI (10-day regimen) and chronic bacterial prostatitis 3

Skin and Soft Tissue Infections

• Levofloxacin is FDA-approved for complicated skin and skin structure infections due to E. faecalis 3
• Uncomplicated infections: 7-14 days of treatment 1

Chronic Bacterial Prostatitis

• Levofloxacin is FDA-approved for chronic bacterial prostatitis due to E. faecalis 3
• Treatment duration typically extends beyond standard courses due to poor prostatic penetration of many antibiotics

Critical Testing Requirements

Always obtain the following susceptibility testing before finalizing therapy: 2

• Penicillin and vancomycin MIC determination
• High-level resistance to gentamicin (to predict synergistic interactions)
• For strains resistant to β-lactams, vancomycin, or aminoglycosides: obtain daptomycin and linezolid susceptibilities 2

Special Considerations for Aminoglycoside Use

Nephrotoxicity Risk Assessment

Patients with enterococcal infections are typically older, debilitated, and may have pre-existing renal failure or complicated urological conditions 2. In these patients:

• Gentamicin-associated nephrotoxicity may significantly complicate standard 4-6 week courses 2
• The risk of attempting to complete gentamicin therapy may exceed the benefit in patients with baseline renal dysfunction 2
• For high-level aminoglycoside-resistant strains, consider double β-lactam regimens for E. faecalis endocarditis 1

Increasing Aminoglycoside Resistance

• Approximately 26-50% of E. faecalis endocarditis cases now involve high-level aminoglycoside-resistant strains 2
• Aminoglycoside-containing regimens are ineffective for these patients 2

Critical Pitfalls to Avoid

• Never use cephalosporins alone for enterococcal coverage, as they have no intrinsic activity against enterococci despite potential in vitro synergy when combined with ampicillin 1, 4
• Do not prescribe vancomycin empirically for E. faecalis when ampicillin susceptibility is likely, as ampicillin is superior and vancomycin should be reserved for documented β-lactam allergy or resistance 1
• Never use aminoglycosides as monotherapy, as enterococci have intrinsic low-level resistance and aminoglycosides alone are ineffective 2, 4
• Avoid treating colonization (e.g., E. faecalis in sputum without true pneumonia), as unnecessary antibiotic exposure promotes resistance without clinical benefit 4
• Always verify the antibiogram and adjust therapy when culture and sensitivity results become available 1

When to Obtain Infectious Disease Consultation

Obtain ID consultation for: 1

• All cases of enterococcal endocarditis (standard of care)
• Vancomycin-resistant enterococcal infections
• High-level aminoglycoside-resistant strains requiring alternative regimens
• Lack of clinical improvement after 48-72 hours of appropriate therapy 1

Monitoring Treatment Response

• Verify clinical improvement within 48-72 hours of initiating therapy 1, 4
• If no improvement occurs, consider resistance, alternative diagnosis, or inadequate source control 1, 4
• Check the antibiogram and consider resistance patterns if clinical response is inadequate 1