What is the recommended treatment for a patient with Enterococcus bacteremia?

Treatment of Enterococcus Bacteremia

For ampicillin-susceptible Enterococcus bacteremia, ampicillin 2g IV every 6 hours for 7-14 days is the preferred treatment, with mandatory catheter removal if present and transesophageal echocardiography if bacteremia persists beyond 72 hours. 1, 2

Initial Antibiotic Selection Based on Susceptibility

Ampicillin-Susceptible Enterococci

• Ampicillin 2g IV every 6 hours is the drug of choice, with clinical and microbiological eradication rates of 88.1% and 86% respectively 3, 2
• Vancomycin should be reserved for patients with documented beta-lactam allergy 1, 2
• The role of adding an aminoglycoside (gentamicin) for uncomplicated bacteremia without endocarditis remains unresolved, though combination therapy is standard for endocarditis 1

Vancomycin-Resistant Enterococci (VRE)

• Linezolid 600 mg IV or PO every 12 hours is the first-line treatment for VRE bacteremia, with clinical cure rates of 81.4% and microbiological cure rates of 86.4% 1, 3, 4
• High-dose daptomycin 8-12 mg/kg/day IV is an alternative for VRE bacteremia 1, 3
• For VRE with high daptomycin MICs (≥3 μg/mL), combination therapy with daptomycin plus ampicillin or ceftaroline demonstrates superior synergistic bactericidal activity compared to monotherapy 5, 2

Treatment Duration

Uncomplicated Bacteremia

• 7-14 days of therapy is recommended when source control is achieved and the catheter is removed 1, 2
• Follow-up blood cultures should be obtained to document clearance of bacteremia 2

Complicated Bacteremia or Endocarditis

• At least 6 weeks of therapy is required for complicated bacteremia or confirmed endocarditis 1, 2
• For prosthetic valve endocarditis, 6 weeks of combination therapy (cell wall-active agent plus gentamicin for the entire duration) is recommended 1

Mandatory Source Control

Catheter Management

• All short-term intravascular catheters must be removed immediately 1, 2
• Long-term catheters should be removed if any of the following are present: insertion site infection, suppurative thrombophlebitis, sepsis, endocarditis, persistent bacteremia >72 hours, or metastatic infection 1
• If a long-term catheter must be retained, antibiotic lock therapy should be added to systemic therapy 1

Evaluation for Endocarditis

Indications for Transesophageal Echocardiography (TEE)

TEE is mandatory in the following scenarios: 1, 2

• New cardiac murmur or embolic phenomena
• Prolonged bacteremia or fever >72 hours despite appropriate antimicrobial therapy
• Radiographic evidence of septic pulmonary emboli
• Presence of prosthetic valve or other endovascular foreign bodies
• Any signs or symptoms suggesting endocarditis

The risk of endocarditis complicating enterococcal bacteremia is relatively low (1.5% in one multicenter study of >205 cases), but the consequences of missing this diagnosis are severe 1

Critical Monitoring Requirements

For Linezolid Therapy

• Weekly complete blood counts are mandatory when using linezolid for >2 weeks due to myelosuppression risk, particularly thrombocytopenia 3, 2

For High-Dose Daptomycin Therapy

• Weekly CPK levels throughout therapy are required due to significant myopathy risk 5, 3, 2
• Discontinue immediately if CPK rises significantly or if muscle pain/weakness develops 5

Common Pitfalls to Avoid

Ineffective Empirical Therapy

• Cephalosporins and aminoglycosides as monotherapy are completely ineffective against enterococci, leading to high rates of treatment failure 2, 6
• In one multicenter study, 43% of empirical antibiotic therapies were inefficient for enterococcal bacteremia 6
• Enterococci are inherently resistant to all cephalosporins despite in vitro susceptibility testing 1, 7

Inadequate Daptomycin Dosing

• Standard doses of daptomycin (6 mg/kg/day) are inadequate for treating resistant E. faecium; higher doses (10-12 mg/kg/day) are required 5, 2
• Daptomycin monotherapy has been associated with treatment failures and development of resistance during therapy 5, 2

Failure to Achieve Source Control

• Failure to remove infected devices or achieve source control will likely result in treatment failure regardless of antibiotic choice 2
• Persistent bacteremia >72 hours after appropriate antibiotic initiation mandates catheter removal 1

Infectious Disease Consultation

Management of enterococcal bacteremia should always involve infectious disease consultation as the standard of care, particularly for: 1, 5, 3

• VRE infections
• Multidrug-resistant strains
• Treatment failures or relapsed infections
• Bacteremia with high-level aminoglycoside resistance
• Any case requiring combination therapy decisions