Spectrum Comparison: Amoxicillin vs. Amoxicillin/Clavulanate
Amoxicillin/clavulanate (Amoxil-Clav, Augmentin) provides significantly broader antibacterial coverage than amoxicillin alone by adding protection against beta-lactamase-producing organisms, which is the critical difference between these agents. 1, 2
Key Spectrum Differences
Organisms Covered by BOTH Agents
- Streptococcus pneumoniae (including penicillin-susceptible strains) 3, 1
- Streptococcus pyogenes and other streptococci 1
- Non-beta-lactamase-producing Haemophilus influenzae 3
- Enterococcus faecalis 1
Additional Coverage with Amoxicillin/Clavulanate
The clavulanate component extends coverage to include:
- Beta-lactamase-producing Haemophilus influenzae (major advantage, as 20-40% of strains produce beta-lactamase) 3, 1, 2
- Moraxella catarrhalis (nearly 100% produce beta-lactamase) 3, 1
- Beta-lactamase-producing Staphylococcus aureus 1, 4
- Anaerobes including Bacteroides fragilis 1, 5
- Beta-lactamase-producing Enterobacteriaceae (E. coli, Klebsiella, Proteus) 1, 4
- Enterobacter species 1
Clinical Efficacy Implications
Calculated Clinical Efficacy Rates
For adults with acute bacterial rhinosinusitis:
- High-dose amoxicillin/clavulanate: 91-92% clinical efficacy 3
- Amoxicillin alone: 86-87% clinical efficacy 3
For children with acute bacterial rhinosinusitis:
- High-dose amoxicillin/clavulanate (90 mg/6.4 mg/kg/day): 91-92% clinical efficacy 3
- Amoxicillin alone (90 mg/kg/day): 82-87% clinical efficacy 3
When Amoxicillin Alone is Adequate
- Mild community-acquired infections in patients without recent antibiotic exposure 3
- Streptococcal pharyngitis (Group A Strep does not produce beta-lactamase) 1
- Dental infections as first-line therapy (500 mg three times daily for 5 days) 6
- Geographic areas with low beta-lactamase prevalence 3
When Amoxicillin/Clavulanate is Required
- Recent antibiotic use (within 4-6 weeks) - risk factor for resistant organisms 3
- Moderate to severe respiratory infections 3
- Failure of amoxicillin therapy after 72 hours 3, 6
- Mild community-acquired intra-abdominal infections 3
- Suspected beta-lactamase-producing organisms 3, 2
- Skin and soft tissue infections where Staphylococcus aureus is suspected 1, 7
Mechanism of Spectrum Extension
Clavulanic acid is a beta-lactamase inhibitor that inactivates plasmid-mediated beta-lactamases, protecting amoxicillin from enzymatic degradation 1, 5. This mechanism does not enhance amoxicillin's intrinsic activity against susceptible organisms but prevents resistance in beta-lactamase producers 3, 5.
Important Limitations of Both Agents
Neither agent provides adequate coverage for:
- Pseudomonas aeruginosa 3
- Methicillin-resistant Staphylococcus aureus (MRSA) 1
- Atypical respiratory pathogens (Mycoplasma, Chlamydia, Legionella) 3
- Extended-spectrum beta-lactamase (ESBL)-producing organisms (requires carbapenems) 3
Common Pitfalls to Avoid
Avoid using amoxicillin/clavulanate when amoxicillin alone would suffice, as the clavulanate component increases adverse effects (particularly diarrhea) and cost without added benefit in beta-lactamase-negative infections 8. The combination should be reserved for resistant bacteria, not used routinely as first-line therapy 8.
Avoid underdosing in areas with high penicillin-resistant S. pneumoniae prevalence - use high-dose formulations (4 g/250 mg daily for adults; 90 mg/6.4 mg/kg/day for children) to overcome relative resistance 3, 2.
Recognize that amoxicillin/clavulanate has superior gram-negative coverage (91-92% efficacy) compared to alternatives like clindamycin (79% efficacy), which has poor activity against H. influenzae and M. catarrhalis 9.