What are the recommended antibiotics for enterococcus (bacteria) positive blood cultures?

Treatment of Enterococcus Bacteremia

Ampicillin 2g IV every 6 hours is the preferred first-line treatment for ampicillin-susceptible enterococcal bacteremia, with vancomycin reserved for ampicillin-resistant strains or patients with beta-lactam allergy. 1

Initial Antibiotic Selection

For Ampicillin-Susceptible Enterococci

• Ampicillin 2g IV every 4-6 hours is the drug of choice for ampicillin-susceptible Enterococcus faecalis and E. faecium 2, 1
• Ampicillin is preferred over all other agents when enterococci are susceptible and patients can tolerate them 3
• For patients transitioning to oral therapy after source control, amoxicillin 500 mg orally every 8 hours is appropriate 4

For Ampicillin-Resistant Enterococci

• Vancomycin is the alternative for ampicillin-resistant strains or patients unable to tolerate beta-lactams 2, 1
• For vancomycin-resistant enterococci (VRE), linezolid 600 mg IV every 12 hours or daptomycin are recommended 2, 1
• Daptomycin should be used at higher doses (10-12 mg/kg/day) for resistant E. faecium, as standard doses (6 mg/kg/day) are inadequate 1

Critical Management Principles

Source Control is Mandatory

• Remove infected catheters immediately for catheter-related bloodstream infections, especially short-term catheters 2, 1
• Failure to achieve source control will likely result in treatment failure regardless of antibiotic choice 1
• For long-term catheters that cannot be removed, add antibiotic lock therapy to systemic antibiotics 2, 1

Evaluation for Endocarditis

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

• New cardiac murmur or embolic phenomena
• Prolonged bacteremia or fever >72 hours despite appropriate antibiotics
• Radiographic evidence of septic pulmonary emboli
• Presence of prosthetic valve or other endovascular foreign bodies

Treatment Duration

Uncomplicated Bacteremia

• 7-14 days of therapy when source control is achieved 2, 4, 1
• Obtain follow-up blood cultures within 48-72 hours to document clearance 4, 1

Complicated Bacteremia or Endocarditis

• At least 6 weeks of therapy is required for endocarditis or complicated infections 2, 1
• For native valve endocarditis with ampicillin plus gentamicin, either 4 or 6 weeks is reasonable depending on symptom duration 2
• For prosthetic valve endocarditis, 6 weeks minimum is required 2

Special Considerations for Endocarditis

Aminoglycoside-Susceptible Strains

• Ampicillin 2g IV every 4 hours plus gentamicin is the traditional synergistic regimen 2
• The role of combination therapy for bacteremia without endocarditis remains unresolved 2

Aminoglycoside-Resistant Strains

• Ampicillin-ceftriaxone combination is reasonable for gentamicin-resistant, streptomycin-susceptible strains 2
• Ampicillin 2g IV every 4 hours plus ceftriaxone 2g IV every 12 hours for 6 weeks 2
• This double beta-lactam regimen has lower nephrotoxicity risk compared to aminoglycoside-containing regimens 2

Vancomycin-Based Regimens

• Vancomycin plus gentamicin for 6 weeks is reasonable when beta-lactams cannot be used 2
• Combinations of penicillin or ampicillin with gentamicin are preferable to vancomycin-gentamicin due to increased ototoxicity and nephrotoxicity risk 2

Treatment of Vancomycin-Resistant Enterococci (VRE)

First-Line Options for VRE

• Linezolid 600 mg IV every 12 hours has demonstrated 92.6% cure rates for VRE infections 2, 5
• Daptomycin at high doses (10-12 mg/kg/day) is effective, particularly when combined with ampicillin 1, 6

Combination Therapy for Resistant Strains

• Daptomycin plus ampicillin shows synergistic activity against ampicillin- and vancomycin-resistant E. faecium 1, 6
• Ampicillin enhances daptomycin killing by reducing bacterial surface charge, even when the organism is ampicillin-resistant 6
• High-dose daptomycin (12 mg/kg) plus ampicillin cleared refractory bacteremia within 24 hours in documented cases 6

Critical Pitfalls to Avoid

Ineffective Monotherapy

• Cephalosporins and aminoglycosides as monotherapy are ineffective against enterococci and lead to high rates of treatment failure 1
• Cephalosporins have minimal or no activity against enterococci despite appearing active in some automated susceptibility systems 2

Inadequate Daptomycin Dosing

• Standard daptomycin doses (6 mg/kg/day) are inadequate for resistant E. faecium 1
• Daptomycin monotherapy has been associated with treatment failures and emergence of resistance during therapy 1

Monitoring Requirements

• Monitor creatine phosphokinase (CPK) levels weekly for patients receiving daptomycin 1
• Monitor complete blood counts weekly for patients receiving linezolid due to bone marrow suppression risk 1
• Measure aminoglycoside serum concentrations when used to minimize nephrotoxicity and ototoxicity 2

Contraindications to Oral Therapy

Oral therapy is contraindicated in: 4

• Endocarditis or suspected endocarditis
• Persistent bacteremia despite treatment
• Metastatic infections
• Immunocompromised patients

Intra-Abdominal and Healthcare-Associated Infections

High-Risk Patients Requiring Enterococcal Coverage

For critically ill patients with healthcare-associated intra-abdominal infections at high risk for enterococcal infection (immunocompromised, recent antibiotic exposure): 2

• Meropenem 1g IV every 8 hours plus ampicillin 2g IV every 6 hours
• Imipenem/cilastatin 1g IV every 8 hours (has intrinsic activity against ampicillin-susceptible enterococci)
• Piperacillin/tazobactam 4.5g IV every 6 hours (active against ampicillin-susceptible enterococci)

VRE Risk in Healthcare Settings

For patients at risk for VRE (previous enterococcal colonization, immunocompromised, long ICU stay, recent vancomycin exposure): 2

• Linezolid 600 mg IV every 12 hours
• Daptomycin 6 mg/kg IV every 24 hours (higher doses for bacteremia)