What is the coverage of amoxicillin-clavulanate (Amoxyclav)?

Antimicrobial Coverage of Amoxicillin-Clavulanate (Amoxyclav)

Amoxicillin-clavulanate provides broad-spectrum coverage against gram-positive, gram-negative, and anaerobic bacteria, including beta-lactamase-producing organisms, making it effective for various infections including respiratory tract, skin and soft tissue, urinary tract, and intra-abdominal infections. 1

Mechanism of Action and Spectrum

• Amoxicillin-clavulanate combines amoxicillin (a semi-synthetic penicillin) with clavulanic acid (a beta-lactamase inhibitor) that protects amoxicillin from degradation by beta-lactamase enzymes produced by resistant bacteria 1
• The addition of clavulanate extends the spectrum of amoxicillin to include many bacteria that would otherwise be resistant 2

Gram-Positive Coverage:

• Staphylococcus aureus (including beta-lactamase-producing strains) 1
• Staphylococcus epidermidis 1
• Staphylococcus saprophyticus 1
• Streptococcus pneumoniae (including many penicillin-intermediate and some resistant strains) 3
• Streptococcus pyogenes (Group A streptococci) 1
• Viridans group streptococci 1
• Enterococcus faecalis (variable susceptibility) 1

Gram-Negative Coverage:

• Haemophilus influenzae (including beta-lactamase-producing strains) 1
• Moraxella catarrhalis (including beta-lactamase-producing strains) 1
• Escherichia coli (including many beta-lactamase-producing strains) 1
• Klebsiella species (including many beta-lactamase-producing strains) 1
• Enterobacter species (variable susceptibility) 1
• Proteus mirabilis 1
• Eikenella corrodens 1

Anaerobic Coverage:

• Bacteroides species including Bacteroides fragilis 1
• Fusobacterium species 1
• Peptostreptococcus species 1
• Clostridium species (variable susceptibility) 4

Clinical Applications

Respiratory Tract Infections:

• Lower respiratory tract infections caused by beta-lactamase-producing H. influenzae and M. catarrhalis 1
• Community-acquired pneumonia, particularly when concerned about drug-resistant S. pneumoniae 3
• Acute bacterial sinusitis caused by beta-lactamase-producing H. influenzae and M. catarrhalis 1
• Acute otitis media, especially in patients who have recently received antibiotics or have concurrent conjunctivitis 4

Skin and Soft Tissue Infections:

• Effective for mild to moderate skin and soft tissue infections 4
• Recommended for animal and human bite wounds due to coverage of oral flora including Pasteurella and anaerobes 4
• Effective against impetigo and cellulitis 4
• Diabetic foot infections (mild to moderate) 4

Intra-abdominal Infections:

• First-choice for mild to moderate intra-abdominal infections 4
• Provides appropriate coverage for mixed aerobic and anaerobic infections 4

Urinary Tract Infections:

• Effective against beta-lactamase-producing E. coli, Klebsiella species, and Enterobacter species 1

Formulations and Dosing Considerations

• Available in various formulations with different amoxicillin-to-clavulanate ratios 2
• Standard adult dose: 875/125 mg twice daily or 500/125 mg three times daily 5
• High-dose formulations (2000/125 mg twice daily for adults, 90/6.4 mg/kg/day for children) developed to overcome resistance in S. pneumoniae 2, 3
• Pharmacokinetically enhanced formulations maintain higher concentrations over longer periods 6

Clinical Pearls and Caveats

• Should not be used when susceptibility testing shows susceptibility to amoxicillin alone (indicating no beta-lactamase production) 1
• Generally well-tolerated but can cause gastrointestinal side effects (diarrhea, nausea) which may be reduced by taking with food 7
• Higher doses are recommended for infections caused by organisms with reduced susceptibility to penicillin 3
• In diabetic foot infections, amoxicillin-clavulanate provides appropriate coverage for moderate infections with recent antibiotic exposure 4
• For skin and soft tissue infections, amoxicillin-clavulanate provides appropriate gram-positive coverage needed for mild infections 4

Resistance Considerations

• The low propensity to select for resistance mutations contributes to its longevity in clinical use 2
• In areas with high prevalence of penicillin-resistant S. pneumoniae, higher doses may be needed 2
• Remains effective against many beta-lactamase-producing organisms that would be resistant to amoxicillin alone 1