Treatment of Enterococcus faecium Infections Based on Sensitivity
For vancomycin-susceptible E. faecium, use ampicillin, piperacillin-tazobactam, or vancomycin based on individual isolate susceptibility testing; for vancomycin-resistant E. faecium (VRE), linezolid 600 mg IV/PO every 12 hours is the first-line treatment, with high-dose daptomycin (10-12 mg/kg/day) plus a β-lactam as the preferred alternative for bacteremia or endocarditis. 1, 2
Treatment Algorithm by Resistance Pattern
Vancomycin-Susceptible E. faecium
Initial empiric therapy should be directed against E. faecalis rather than E. faecium unless specific risk factors are present (liver transplant recipients with hepatobiliary infections or patients known to be colonized with VRE). 1
For confirmed vancomycin-susceptible E. faecium:
- Ampicillin (if susceptible on testing) 1
- Piperacillin-tazobactam (if susceptible on testing) 1
- Vancomycin (if β-lactam resistant) 1
Vancomycin-Resistant E. faecium (VRE)
For Uncomplicated Infections (UTI, Simple Bacteremia):
Linezolid 600 mg IV or PO every 12 hours is the backbone therapy with an 86.4% microbiological cure rate and 81.4% clinical cure rate in the largest clinical trial. 1, 3
Alternative options for uncomplicated urinary tract infections:
- Fosfomycin 3 g PO single dose 1
- Nitrofurantoin 100 mg PO every 6 hours 1
- High-dose ampicillin 18-30 g IV daily in divided doses (if susceptible) 1
For Complicated Bacteremia or Endocarditis:
High-dose daptomycin 10-12 mg/kg/day IV PLUS ampicillin or ceftaroline is strongly recommended as combination therapy shows synergistic activity and prevents resistance emergence. 1, 2
- Treatment duration: 7-14 days for catheter-related bacteremia with source control; 6 weeks for endocarditis 2
- Obtain transesophageal echocardiography if bacteremia persists >72 hours, signs/symptoms of endocarditis present, or prosthetic valves/intravascular devices present 2
- Linezolid monotherapy is acceptable but less preferred due to bacteriostatic activity; mortality rate 32.8% vs 35.7% for daptomycin in comparative data 1
For Intra-abdominal Infections:
Tigecycline 100 mg IV loading dose then 50 mg IV every 12 hours based on clinical response 1
Alternative: Linezolid 600 mg IV/PO every 12 hours 1
For Endocarditis (Beta-lactam and Gentamicin Susceptible):
Ampicillin 200 mg/kg/day IV in 4-6 doses PLUS ceftriaxone 4 g/day IV in 2 doses for 6 weeks (this combination is active against E. faecalis but NOT E. faecium) 1
For multiresistant VRE faecium endocarditis:
- Daptomycin 10 mg/kg/day plus ampicillin 200 mg/kg/day IV in 4-6 doses 1
- Linezolid 600 mg IV/PO every 12 hours for ≥8 weeks (monitor hematological toxicity) 1
- Quinupristin-dalfopristin 7.5 mg/kg IV every 8 hours for ≥8 weeks (NOT active against E. faecalis, only E. faecium) 1, 4
Site-Specific Considerations
Catheter-Related Bloodstream Infections:
Remove infected catheters, especially short-term catheters 1, 2
For retained long-term catheters: systemic therapy PLUS antibiotic lock therapy 2
Combination therapy with gentamicin and ampicillin is more effective than monotherapy when catheters are retained 1
Prostatitis:
For acute bacterial prostatitis: levofloxacin 500 mg PO daily for 4-6 weeks 5
For ampicillin-resistant strains: vancomycin 5
For VRE prostatitis: linezolid 600 mg PO every 12 hours 5, 6
For chronic E. faecalis prostatitis: pulse therapy with linezolid 2 weeks, 1-week rest, then levofloxacin 2 weeks; repeat 2-3 cycles 6
Critical Monitoring and Pitfalls
Monitor for daptomycin resistance development during therapy by obtaining repeat cultures if clinical response is inadequate; daptomycin monotherapy has been associated with treatment failures and resistance emergence. 2, 7
Standard daptomycin doses (6 mg/kg/day) are inadequate for VRE faecium; higher doses (10-12 mg/kg/day) are required. 2
Monitor CPK levels at least weekly with daptomycin therapy due to skeletal muscle toxicity risk. 1, 7
Monitor complete blood counts weekly with linezolid due to bone marrow suppression risk, particularly with courses >14-21 days. 1, 3
Linezolid is bacteriostatic, not bactericidal, which may limit effectiveness in endovascular infections compared to daptomycin-based regimens. 2
Quinupristin-dalfopristin causes phlebitis in peripheral IV administration; use central venous access when possible. Clinical response rate 70.5% for bacteriologically evaluable VRE infections. 4, 8
Source control is critical for treatment success; failure to remove infected devices or drain abscesses will result in treatment failure regardless of antimicrobial choice. 2
Persistent bacteremia >4 days is independently associated with mortality and warrants evaluation for endocarditis with TEE, particularly in patients with prosthetic valves. 1, 5