What are the appropriate antibiotic (abx) choices for a patient with a suspected Enterococcus faecalis infection?

Antibiotic Treatment for Enterococcus faecalis Infections

First-Line Therapy

Ampicillin 2 g IV every 4-6 hours is the gold standard treatment for susceptible E. faecalis infections (MIC ≤8 mg/L), as recommended by the Infectious Diseases Society of America. 1, 2

• For less severe infections amenable to outpatient treatment, high-dose amoxicillin 1000 mg orally three times daily is appropriate, as it achieves MICs two to four times lower than penicillin G against enterococci 1
• Only 3% of E. faecalis strains are multidrug-resistant, and most retain ampicillin susceptibility 2

Combination Therapy for Serious Infections

For infective endocarditis and other serious infections requiring bactericidal activity, combine ampicillin with an aminoglycoside or ceftriaxone for synergistic killing. 3, 2

Ampicillin + Gentamicin Regimen

• Ampicillin 200 mg/kg/day IV in 4-6 doses PLUS gentamicin 3 mg/kg/day IV or IM in 1 dose 3
• Duration: 4-6 weeks for native valve endocarditis, minimum 6 weeks for prosthetic valve endocarditis 3, 2
• Gentamicin should be given for 2-6 weeks depending on clinical scenario 3
• Monitor serum gentamicin levels and renal function weekly (twice weekly in renal failure) 3

Ampicillin + Ceftriaxone Regimen (Alternative)

• Ampicillin 200 mg/kg/day IV in 4-6 doses PLUS ceftriaxone 4 g/day IV or IM in 2 doses 3
• Duration: 6 weeks for all cases 3
• This combination is active against E. faecalis strains with and without high-level aminoglycoside resistance (HLAR), making it the combination of choice for HLAR E. faecalis endocarditis 3
• Critical caveat: This combination is NOT active against E. faecium 3
• For outpatient parenteral therapy, ceftriaxone 4 g once daily plus ampicillin 2 g every 4 hours via programmable pump has shown clinical and microbiological cure in small case series 4

Important: A 4-week treatment course may be insufficient for uncomplicated native valve endocarditis, as relapses were significantly more frequent (17% vs 2%) compared to 6-week therapy, particularly in cirrhotic patients. 5

Penicillin Allergy or Ampicillin-Resistant Strains

Vancomycin 30 mg/kg/day IV in 2 divided doses is the primary alternative for severe penicillin allergy or ampicillin-resistant E. faecalis. 3, 1, 2

• Combine with gentamicin 3 mg/kg/day IV or IM in 1 dose for 6 weeks for endocarditis 3
• Monitor serum vancomycin trough levels (Cmin) to maintain ≥20 mg/L 3
• Reserve vancomycin for true penicillin allergy due to antimicrobial stewardship concerns 1
• Many vancomycin-resistant E. faecalis remain penicillin-susceptible, so always check susceptibilities 2

Vancomycin-Resistant E. faecalis (VRE)

Linezolid 600 mg IV/PO every 12 hours is the preferred agent for vancomycin-resistant E. faecalis, with proven clinical efficacy and excellent tissue penetration. 1, 2, 6

• Treatment duration: minimum 8 weeks for serious infections 3
• Monitor for hematological toxicity, particularly thrombocytopenia with courses >14-21 days 3, 6
• Clinical cure rates of 92.6% have been demonstrated in VRE infections at various sites 6

Daptomycin 8-12 mg/kg/day IV is an alternative for VRE, though it may have less prostatic penetration for genitourinary infections. 1, 2, 7

• For endocarditis, consider adding ampicillin (if susceptible) at 200 mg/kg/day IV in 4-6 doses for enhanced activity 3
• Monitor plasma CPK levels at least weekly for skeletal myopathy 3
• Some experts recommend adding cloxacillin or fosfomycin to prevent daptomycin resistance development 3

Quinupristin-dalfopristin 7.5 mg/kg every 8 hours is an option for multidrug-resistant E. faecalis, though it is NOT active against E. faecalis in vitro (MIC90 = 16 mcg/mL). 3, 6

Site-Specific Treatment Considerations

Uncomplicated Cystitis

• Amoxicillin 500 mg orally every 8 hours for 7-14 days 1, 2
• Nitrofurantoin is also effective for lower urinary tract infections 6, 8

Chronic Bacterial Prostatitis

• High-dose amoxicillin 1000 mg orally three times daily for 4-6 weeks 1, 9
• Target trough concentrations of 40-80 mg/L to overcome the blood-prostate barrier 9
• For biofilm-embedded infections, consider pulse dosing: 2 weeks on, 1 week off, repeat for 2-3 cycles 9
• Time above MIC (T>MIC) is the key pharmacodynamic parameter 9
• If treatment fails, escalate to ampicillin 2 g IV every 4 hours plus ceftriaxone 2 g IV every 12 hours for 4-6 weeks 9

Healthcare-Associated Infections

• Anti-enterococcal coverage is mandatory when enterococci are recovered from healthcare-associated infections 1
• Coverage is essential for patients with postoperative infections, prior cephalosporin exposure, or prosthetic materials 1

Community-Acquired Biliary Infections

• Anti-enterococcal coverage is NOT required unless the patient is immunosuppressed, as pathogenicity has not been demonstrated in immunocompetent hosts 1

High-Level Aminoglycoside Resistance (HLAR)

• If gentamicin MIC >500 mg/L but susceptible to streptomycin, replace gentamicin with streptomycin 15 mg/kg/day in 2 divided doses 3
• The double β-lactam regimen (ampicillin + ceftriaxone) is reasonable for HLAR E. faecalis endocarditis 3, 2

Critical Pitfalls to Avoid

Never use cephalosporins alone for enterococcal coverage—they have no intrinsic activity against enterococci despite in vitro synergy when combined with ampicillin. 1, 2

Do not prescribe vancomycin empirically for E. faecalis when ampicillin is superior and should be preferred unless there is documented beta-lactam allergy. 2

Do not assume E. faecium has the same susceptibility profile as E. faecalis—E. faecium has intrinsic penicillin resistance and requires different empiric coverage. 2

Avoid empiric coverage for vancomycin-resistant E. faecium unless the patient is at very high risk (liver transplant with hepatobiliary source, known VRE colonization). 1

Always obtain infectious disease consultation for enterococcal endocarditis management as standard of care. 2