What is the treatment for Enterococcus bacteremia?

Treatment of Enterococcus Bacteremia (Non-Endocarditis)

For ampicillin-susceptible Enterococcus bacteremia, ampicillin 2g IV every 6 hours is the preferred treatment for 7-14 days with catheter removal when applicable. 1, 2

Initial Antimicrobial Selection

Ampicillin-Susceptible Strains

• Ampicillin is the drug of choice for ampicillin-susceptible enterococci, particularly E. faecalis (which is uniformly susceptible in >98% of cases). 3, 1, 4
• Dosing: Ampicillin 2g IV every 6 hours. 2
• For beta-lactam allergic patients, vancomycin is the appropriate alternative. 2

Ampicillin-Resistant Strains

• Vancomycin should be used if the pathogen is resistant to ampicillin. 3, 1, 4
• Note that 91.2% of E. faecium isolates are ampicillin-resistant, whereas E. faecalis is typically susceptible. 5
• Nosocomial acquisition strongly predicts ampicillin resistance (OR 13.6; 95% CI 3.16-58.3). 5

Vancomycin-Resistant Enterococci (VRE)

• Linezolid or daptomycin should be used based on antibiotic susceptibility results. 3, 1
• Linezolid is FDA-approved for VRE infections including concurrent bacteremia. 6
• For resistant E. faecium, high-dose daptomycin (10-12 mg/kg/day) plus ampicillin or ceftaroline may be required, as standard daptomycin doses (6 mg/kg/day) are inadequate. 2

Role of Combination Therapy

The role of combination therapy (cell wall-active agent plus aminoglycoside) for enterococcal bacteremia without endocarditis is unresolved. 3, 4

• Historically, combination therapy with ampicillin plus gentamicin showed 90% response rates, but single-drug therapy also achieved 89% response in retrospective analysis. 7
• Combination therapy is definitively indicated for endocarditis but not established as necessary for uncomplicated bacteremia. 3, 4
• Monotherapy with ampicillin or vancomycin is adequate for most non-endocarditis bacteremia cases. 3, 7

Treatment Duration

For uncomplicated enterococcal bacteremia with source control achieved, treat for 7-14 days. 3, 1, 2

• This applies when short-term catheters are removed or when long-term catheters are retained with antibiotic lock therapy. 3, 1
• For complicated bacteremia or when endocarditis is present, at least 6 weeks of therapy is required. 2
• Obtain follow-up blood cultures to document clearance of bacteremia. 2

Catheter Management

Short-Term Catheters

• Removal of infected short-term intravascular catheters is mandatory. 3, 1, 2

Long-Term Catheters

• Remove long-term catheters in cases of: 3, 1

  • Insertion site or pocket infection
  • Suppurative thrombophlebitis
  • Sepsis
  • Persistent bacteremia (>72 hours after appropriate antibiotic initiation)
  • Metastatic infection

• If the long-term catheter is retained, antibiotic lock therapy must be used in addition to systemic therapy. 3, 1, 2

• Failure to remove infected devices when indicated will likely result in treatment failure. 2

Evaluation for Endocarditis

Perform transesophageal echocardiography (TEE) if: 3, 1, 2

• New murmur or embolic phenomena are present
• Prolonged bacteremia or fever persists >72 hours despite appropriate antimicrobial therapy
• Radiographic evidence of septic pulmonary emboli exists
• Prosthetic valve or other endovascular foreign bodies are present

The risk of endocarditis complicating enterococcal bacteremia is relatively low (1.5% in VRE cases), but missing this diagnosis has severe consequences. 3

Monitoring Requirements

• For linezolid: Monitor complete blood counts weekly due to risk of bone marrow suppression. 2
• For daptomycin: Monitor creatine phosphokinase levels weekly. 2
• For vancomycin: Therapeutic drug monitoring is required, unlike linezolid. 2

Critical Pitfalls to Avoid

• Do NOT use cephalosporins or aminoglycosides as monotherapy—enterococci are intrinsically resistant to cephalosporins, leading to high rates of inefficient empirical therapy. 4, 2
• Do NOT use linezolid empirically when bacteremia is suspected but not confirmed—patients without documented bacteremia had significantly worse survival with linezolid (HR 2.20; 95% CI 1.07-4.50). 3, 2
• Do NOT fail to remove infected catheters when indicated—this is the most common cause of treatment failure. 2
• Do NOT miss endocarditis—failure to perform TEE when indicated can result in inadequate treatment duration and poor outcomes. 1, 2
• Do NOT use standard-dose daptomycin for resistant E. faecium—higher doses (10-12 mg/kg/day) are required, and monotherapy has been associated with treatment failures and resistance development. 2

Special Clinical Scenarios

• Bacteremia from unknown source is associated with increased 30-day mortality (HR 4.17 for E. faecalis; HR 2.91 for E. faecium) and warrants empirical glycopeptide therapy if severe infection is suspected. 5
• Increased Pitt bacteremia score independently predicts mortality (HR 1.27-1.36 per point increase). 5
• Enterococcal bacteremia persisting >4 days has been independently associated with increased mortality. 1