What is the treatment for Enterococcus bacteremia?

Treatment of Enterococcus Bacteremia

For ampicillin-susceptible Enterococcus faecalis bacteremia, ampicillin is the preferred first-line treatment, while vancomycin should be used for ampicillin-resistant strains, and linezolid or daptomycin (based on susceptibility testing) for vancomycin-resistant enterococci. 1, 2

Initial Antimicrobial Selection

Ampicillin-Susceptible Strains

• Ampicillin is the drug of choice for ampicillin-susceptible enterococci, particularly E. faecalis, which represents the majority of community-acquired cases 1, 2, 3
• Piperacillin-tazobactam is an acceptable alternative for ampicillin-susceptible strains based on individual susceptibility testing 1, 3
• Recent data demonstrate that amoxicillin use in documented therapy is independently associated with better short-term outcomes (p = 0.001) 4

Ampicillin-Resistant Strains

• Vancomycin is the recommended alternative when the pathogen is resistant to ampicillin 1, 2
• This applies primarily to E. faecium, where 60% of nosocomial bloodstream infections demonstrate vancomycin resistance 1

Vancomycin-Resistant Enterococci (VRE)

• Linezolid 600 mg IV/PO every 12 hours is first-line therapy for VRE bacteremia 1, 3, 5
• High-dose daptomycin (10-12 mg/kg/day) is the preferred alternative, particularly for bacteremia or endocarditis 3, 6
• Standard daptomycin doses (6 mg/kg/day) are inadequate for VRE; higher doses are required 3
• Quinupristin-dalfopristin (7.5 mg/kg IV every 8 hours) may be used for E. faecium but has limited activity against E. faecalis 1, 3

Treatment Duration

Uncomplicated Bacteremia

• A 7-14 day course is recommended for uncomplicated enterococcal bacteremia when the catheter is removed or when antibiotic lock therapy is used with catheter retention 1, 2

Complicated Bacteremia

• Longer treatment courses (≥8 weeks) are required for endocarditis or metastatic infections 2, 3
• Enterococcal bacteremia persisting >4 days is independently associated with increased mortality and warrants extended evaluation 1, 2

Catheter Management

Short-Term Catheters

• Removal of infected short-term intravascular catheters is recommended 1, 2

Long-Term Catheters

• Remove long-term catheters in cases of insertion site/pocket infection, suppurative thrombophlebitis, endovascular infection, or sepsis 1, 2
• If the catheter is retained, antibiotic lock therapy must be used in addition to systemic therapy 1, 2
• Obtain follow-up blood cultures and remove the catheter if persistent bacteremia (>72 hours after appropriate therapy initiation) is detected 1, 2

Evaluation for Endocarditis

Perform transesophageal echocardiography (TEE) if any of the following are present: 1, 2

• New 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
• Bacteremia persisting >4 days 1, 2

The risk of endocarditis complicating enterococcal catheter-related bloodstream infection is relatively low (1.5% in one multicenter study), but TEE is critical when clinical suspicion exists 1

Role of Combination Therapy

• The role of combination therapy (cell wall-active antimicrobial plus aminoglycoside) for enterococcal bacteremia without endocarditis remains unresolved 1
• One large series found combination therapy with gentamicin and ampicillin more effective than monotherapy when the catheter was retained 1
• For aminoglycoside-resistant strains with endocarditis, ampicillin 2 g IV every 4 hours plus ceftriaxone 2 g IV every 12 hours for 6 weeks is an alternative 7

Timing of Appropriate Therapy

Early effective therapy is critical for survival:

• Inappropriate antibiotic therapy is independently associated with 30-day mortality (p = 0.003) 8
• Effective antibiotic therapy should be initiated within 48 hours of blood culture collection to achieve 30-day mortality rates below 33% 9
• Delayed appropriate therapy significantly increases mortality: 54% 30-day mortality with inappropriate antibiotics versus 26% with appropriate therapy 8
• Median survival with inappropriate antibiotics is 1 month versus 11 months with appropriate therapy 8

Monitoring Requirements

For Daptomycin

• Monitor CPK levels at least weekly due to skeletal muscle toxicity risk 3
• Obtain repeat cultures if clinical response is inadequate to assess for resistance development 3

For Linezolid

• Monitor complete blood counts weekly due to bone marrow suppression risk, particularly with courses >14-21 days 3, 5
• The safety and efficacy of linezolid beyond 28 days have not been established in controlled trials 5

Critical Pitfalls to Avoid

• Failure to initiate appropriate therapy within 48 hours: 43% of empirical therapies and 17% of documented therapies are inefficient for enterococcal bacteremia 4, 9
• Using standard-dose daptomycin for VRE: Doses of 10-12 mg/kg/day are required, not the standard 6 mg/kg/day 3, 6
• Not removing infected catheters when indicated: Source control is critical; failure to remove devices or drain abscesses results in treatment failure regardless of antimicrobial choice 3
• Missing endocarditis: Transthoracic echocardiography findings are insufficient to rule out infective endocarditis; TEE is required when indicated 1, 2
• Inadequate treatment duration: Particularly problematic in cases with endovascular infection 2
• Ignoring vancomycin tolerance: Some E. faecalis strains may be vancomycin-tolerant (low MIC but high MBC), requiring alternative therapy such as high-dose daptomycin 6