Does Augmentin (amoxicillin-clavulanate) cover Methicillin-resistant Staphylococcus aureus (MRSA)?

Augmentin Does Not Cover MRSA

Augmentin (amoxicillin-clavulanate) is not effective against methicillin-resistant Staphylococcus aureus (MRSA) and should not be used for infections where MRSA is suspected or confirmed. 1

Mechanism of Resistance

MRSA possesses the mecA gene, which encodes for a penicillin-binding protein (PBP2a) with reduced affinity for all β-lactam antibiotics, including amoxicillin-clavulanate. This mechanism differs from the β-lactamase production that clavulanate inhibits:

• While clavulanate effectively inhibits standard β-lactamases, it cannot overcome the PBP2a-mediated resistance in MRSA 2
• The altered penicillin-binding protein in MRSA has low affinity for all commercially available β-lactams, rendering Augmentin ineffective 2

Appropriate Antibiotics for MRSA

For infections where MRSA is suspected or confirmed, the following antibiotics should be used instead:

1. First-line therapy: Vancomycin for serious MRSA infections 1
2. Alternatives:
   • Linezolid
   • Daptomycin (for non-pulmonary infections)
   • Trimethoprim-sulfamethoxazole (for less severe infections)
   • Clindamycin (if susceptible)

When to Consider MRSA Coverage

According to the Infectious Diseases Society of America (IDSA), empiric MRSA coverage should be initiated in the following scenarios 2:

• Patient has a history of previous MRSA infection or colonization within the past year
• Local prevalence of MRSA is high (approximately 50% for mild infections, 30% for moderate infections)
• The infection is severe enough that treatment failure would pose an unacceptable risk

Augmentin's Actual Spectrum of Activity

Augmentin is effective against:

• Methicillin-susceptible Staphylococcus aureus (MSSA)
• β-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis
• Streptococcus species
• Many common gram-negative organisms 3

Experimental Evidence

While some older experimental studies suggested potential activity of high-dose amoxicillin-clavulanate against certain MRSA strains in animal models 4, 5, these findings have not translated to clinical practice. A 1994 study explicitly stated that "usage of amoxycillin/clavulanate against MRSA is still experimental and is not currently advocated for the treatment of MRSA infections in humans" 5.

Clinical Implications

When treating skin and soft tissue infections or other conditions where MRSA is a concern:

1. Assess risk factors for MRSA (previous infection, healthcare exposure, local prevalence)
2. If MRSA is suspected, choose appropriate anti-MRSA therapy
3. Obtain cultures when possible to guide definitive therapy
4. Consider local antibiograms when selecting empiric therapy

Common Pitfalls to Avoid

• Assuming Augmentin covers MRSA because it contains a β-lactamase inhibitor
• Using Augmentin for empiric therapy in settings with high MRSA prevalence
• Failing to obtain appropriate cultures before starting antibiotics
• Not considering local resistance patterns when selecting empiric therapy

In conclusion, while Augmentin remains a valuable broad-spectrum antibiotic for many community-acquired infections, it should not be relied upon for coverage of MRSA infections.