Oral Penicillin for Enterococcus faecalis Infections
Oral penicillin is NOT effective for treating Enterococcus faecalis infections because enterococci are intrinsically resistant to penicillin monotherapy—these organisms are only inhibited but not killed by penicillin alone, requiring combination therapy with an aminoglycoside or second beta-lactam to achieve bactericidal activity. 1
Why Penicillin Monotherapy Fails
- Enterococci demonstrate relative resistance to penicillin and ampicillin, meaning these agents are bacteriostatic rather than bactericidal when used alone 1
- The mechanism involves low-affinity penicillin-binding proteins that prevent adequate bacterial killing with monotherapy 2
- Enterococci are relatively impermeable to single agents, requiring synergistic combinations to achieve therapeutic concentrations at the ribosomal target 1
Required Treatment Approach
For Susceptible E. faecalis Strains
Combination therapy is mandatory for all serious E. faecalis infections:
- Penicillin G or ampicillin PLUS gentamicin for 4-6 weeks is the standard regimen for native valve endocarditis 1
- The aminoglycoside must be continued for the entire treatment duration (not just 2 weeks as with streptococcal infections) 1
- For prosthetic valve involvement, extend therapy to a minimum of 6 weeks 1
Alternative Combination Regimens
- Ampicillin plus ceftriaxone for 6 weeks is effective for aminoglycoside-resistant E. faecalis strains 1
- This dual beta-lactam approach works by saturating different penicillin-binding proteins simultaneously 3
- Never use ceftriaxone alone—enterococci are resistant to all cephalosporins as monotherapy 1, 4
Critical Pitfalls to Avoid
- Do not prescribe oral penicillin for any enterococcal infection—the route of administration is irrelevant when the fundamental problem is lack of bactericidal activity 4
- Ampicillin is superior to penicillin for E. faecalis due to lower MICs, though both require combination therapy 4
- Always obtain infectious disease consultation for enterococcal endocarditis as standard of care 1, 4
When Oral Therapy Might Be Considered
For uncomplicated urinary tract infections only (not endocarditis or bacteremia):
- High-dose oral amoxicillin 1000 mg three times daily for 7-14 days may be used for susceptible strains 5
- Alternative oral options include fosfomycin 3g single dose or nitrofurantoin 100 mg every 6 hours 6
- These are appropriate only for cystitis in stable patients without systemic involvement 5
Monitoring Requirements
- Verify susceptibility testing for ampicillin, vancomycin, and high-level aminoglycoside resistance before finalizing therapy 5
- Monitor renal function and aminoglycoside levels weekly when using gentamicin-based regimens 1
- Obtain repeat cultures if clinical response is inadequate to detect emerging resistance 6