Does amoxicillin‑clavulanate provide coverage for Enterococcus species?

Does Amoxicillin-Clavulanate Cover Enterococcus?

Yes, amoxicillin-clavulanate provides excellent coverage for Enterococcus faecalis, with 100% in vitro susceptibility demonstrated in multiple studies, but it has unreliable activity against Enterococcus faecium, particularly ampicillin-resistant strains. 1, 2

Spectrum of Activity by Species

Enterococcus faecalis

• Amoxicillin-clavulanate demonstrates 100% susceptibility against E. faecalis isolates, making it a highly reliable option for infections caused by this species 2, 3
• The FDA label confirms activity against E. faecalis, listing it among organisms with at least 90% susceptibility to amoxicillin-clavulanate 1
• Research from periodontal isolates showed all E. faecalis strains were susceptible to amoxicillin-clavulanate, compared to only 46.8% susceptibility to tetracycline and 19.2% to erythromycin 2

Enterococcus faecium

• E. faecium shows variable and often poor susceptibility to amoxicillin-clavulanate, particularly in ampicillin-resistant strains 4
• Automated susceptibility testing systems may falsely report E. faecium as susceptible to amoxicillin-clavulanate when strains are actually ampicillin-resistant, with MIC values obtained by standard methods being significantly higher (≥16/8 mg/L) than automated results (≤4/2 mg/L) 4
• If E. faecium is resistant to ampicillin, it must be considered resistant to amoxicillin-clavulanate regardless of automated testing results 4

Clinical Context and Guidelines

Intra-Abdominal Infections

• The WHO 2024 guidelines list amoxicillin-clavulanate as a first-choice agent for mild-to-moderate intra-abdominal infections, where enterococcal coverage is often desired 5
• When using regimens that don't inherently cover enterococcus (such as ceftriaxone-metronidazole), ampicillin should be added specifically for enterococcal coverage 5
• Multiple randomized trials comparing regimens with and without enterococcal coverage showed no advantage for routine enterococcal treatment in community-acquired intra-abdominal infections 5

When Enterococcal Coverage Matters

• Enterococcal coverage becomes clinically important in nosocomial postoperative infections, where broader regimens are recommended 5
• High-risk patients (APACHE II ≥15, immunosuppressed, inadequate source control) may benefit from enterococcal coverage 5
• For serious enterococcal infections requiring bactericidal activity, combination therapy with ampicillin plus gentamicin is preferred over amoxicillin-clavulanate alone 6

Practical Considerations

Dosing for Enterococcal Coverage

• Standard dosing of amoxicillin-clavulanate (875/125 mg twice daily in adults) is adequate for E. faecalis 1
• High-dose formulations (4g amoxicillin/250mg clavulanate daily for adults; 90mg/kg amoxicillin/6.4mg/kg clavulanate for children) are designed primarily for resistant Streptococcus pneumoniae, not enterococci 5

Critical Pitfalls

• Never rely on automated susceptibility testing alone for E. faecium—confirm ampicillin susceptibility first, as ampicillin resistance predicts amoxicillin-clavulanate resistance 4
• The addition of clavulanate does not enhance activity against enterococci compared to ampicillin or amoxicillin alone, as enterococcal resistance is not mediated by beta-lactamases 1, 6
• For vancomycin-resistant enterococci (VRE), amoxicillin-clavulanate is not appropriate; consider daptomycin, linezolid, or tigecycline depending on infection site 5

Alternative Agents

• Ampicillin remains the drug of choice for documented enterococcal infections, particularly E. faecalis 5, 7
• Ciprofloxacin showed 89.4% susceptibility against periodontal E. faecalis isolates, making it a potential alternative in penicillin-allergic patients 2
• For urinary tract infections caused by ampicillin-resistant VRE, high-dose ampicillin (18-30g IV daily) or amoxicillin (500mg every 8 hours) may still achieve sufficient urinary concentrations 5