Key Difference Between Amoxicillin and Augmentin
Augmentin (amoxicillin-clavulanate) contains clavulanic acid, a β-lactamase inhibitor that prevents bacterial enzymes from destroying amoxicillin, making it effective against β-lactamase-producing bacteria that would otherwise resist plain amoxicillin. 1
Mechanism and Spectrum of Activity
Amoxicillin alone is a broad-spectrum penicillin effective against many gram-positive and gram-negative bacteria, but it is destroyed by β-lactamase enzymes produced by resistant organisms 2
Augmentin's clavulanic acid irreversibly binds to and inactivates β-lactamase enzymes, preserving amoxicillin's antibacterial activity against organisms that would otherwise be resistant 1, 2
This combination extends coverage to include β-lactamase-producing strains of Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus 3, 1
Clinical Significance: When Augmentin is Superior
E. coli Infections (Especially Urinary Tract Infections)
Approximately 75% (range 45-100%) of E. coli urinary isolates are resistant to amoxicillin alone, according to Global Antimicrobial Resistance Surveillance System data 4
The WHO recommends amoxicillin-clavulanate as first-choice treatment for lower urinary tract infections, having removed amoxicillin from recommendations in 2021 due to high resistance rates 5, 4
Continuing amoxicillin alone for E. coli infections is associated with prolonged illness duration 4
Respiratory Tract Infections
For acute bacterial rhinosinusitis, Augmentin achieves 91-92% clinical efficacy compared to 86-87% for amoxicillin alone, specifically due to coverage of β-lactamase-producing H. influenzae and M. catarrhalis 5, 3
The American Academy of Otolaryngology recommends Augmentin when β-lactamase-producing organisms or penicillin-resistant S. pneumoniae are suspected 3
For pediatric acute otitis media, particularly recurrent or persistent cases, high-dose Augmentin (90/6.4 mg/kg/day) is considered treatment of choice after amoxicillin failure 6
Skin and Soft Tissue Infections
For animal and human bites, Augmentin is the oral treatment of choice due to coverage of Pasteurella multocida and oral anaerobes 3
For infected skin conditions caused by amoxicillin-resistant Staphylococcus aureus (often β-lactamase producers), Augmentin shows 94% response rates 7
Intra-Abdominal Infections
- For non-critically ill immunocompetent patients with adequate source control, amoxicillin-clavulanate 2g/0.2g every 8 hours is recommended first-line 5
When Amoxicillin Alone Remains Appropriate
Simple streptococcal pharyngitis where Streptococcus pyogenes (which does not produce β-lactamase) is the pathogen 2
Uncomplicated cellulitis or erysipelas without risk factors for β-lactamase-producing organisms 3
Dental infections in patients without recent antibiotic exposure or risk factors for resistant organisms 2
Important Patient-Specific Considerations
Renal Impairment
Both amoxicillin and clavulanate are renally cleared and require dose adjustment in renal impairment 8
Both drugs are removed by hemodialysis 8
Periodic assessment of renal function is advisable during prolonged therapy 8
Allergy Considerations
If a patient has a documented penicillin allergy, neither drug should be used 8
For β-lactam intolerance (non-Type I hypersensitivity like rash), cephalosporins may be considered as alternatives 5
Alternative regimens for β-lactam allergic patients include fluoroquinolones, tigecycline, or eravacycline depending on infection severity 5
Tolerability Differences
Gastrointestinal side effects (nausea 9%, diarrhea 9%) are more common with Augmentin than amoxicillin alone due to the clavulanate component 8, 7
Twice-daily dosing of Augmentin reduces diarrhea frequency compared to three-times-daily dosing 6
The overall adverse event rate remains low (3.6% in large postmarketing studies) 6
Drug Interactions
Both drugs interact with probenecid, resulting in increased and prolonged blood levels 8
Concurrent allopurinol substantially increases rash incidence with both agents 8
Both may reduce oral contraceptive efficacy 8
Common Pitfalls to Avoid
Do not use amoxicillin alone for empiric treatment of urinary tract infections given the 75% resistance rate in E. coli 5, 4
Do not prescribe either drug for patients with mononucleosis, as ampicillin-class antibiotics cause erythematous rash in these patients 8
Do not assume Augmentin covers MRSA, Pseudomonas aeruginosa, or ESBL-producing organisms—it does not 3
Always check local antibiograms when available, as resistance patterns vary geographically 4
Recent antibiotic exposure (within 4-6 weeks) is a risk factor for resistant organisms and favors Augmentin over amoxicillin 5