Is Augmentin (amoxicillin-clavulanate) effective against Staphylococcus aureus infections?

Does Augmentin Cover Staphylococcus aureus Infections?

Augmentin (amoxicillin-clavulanate) is effective ONLY against methicillin-susceptible Staphylococcus aureus (MSSA) that produces beta-lactamase, but it is completely ineffective against methicillin-resistant Staphylococcus aureus (MRSA). 1

FDA-Approved Indication

The FDA label explicitly states that Augmentin is indicated for skin and skin structure infections caused by beta-lactamase-producing isolates of Staphylococcus aureus 1. This means:

• Works for MSSA that produces beta-lactamase (the clavulanate component inhibits the beta-lactamase enzyme that would otherwise destroy amoxicillin) 1
• Does NOT work for MRSA (methicillin resistance is a completely different mechanism unrelated to beta-lactamase production) 2, 3

Critical Clinical Decision Point

Before prescribing Augmentin for a suspected staph infection, you must determine:

1. Is this MSSA or MRSA? If MRSA is suspected or confirmed, Augmentin will fail completely 2, 3
2. Does the MSSA strain produce beta-lactamase? The FDA label specifies that when susceptibility testing shows the organism is susceptible to amoxicillin alone (indicating no beta-lactamase production), Augmentin should not be used 1

When Augmentin Works for Staph Infections

Augmentin is appropriate for:

• Community-acquired skin infections where MSSA is likely and local MRSA prevalence is low 4, 5
• Mixed infections with beta-lactamase-producing S. aureus and Streptococcus pyogenes (Augmentin covers both organisms, whereas amoxicillin alone would fail due to beta-lactamase inactivation) 5
• Animal or human bite wounds where S. aureus may be present alongside other organisms 6

Clinical studies from the 1980s showed 94% response rates in skin infections caused by amoxicillin-resistant (beta-lactamase-producing) S. aureus 4.

When Augmentin Fails Completely

Never use Augmentin for:

• MRSA infections - Research demonstrates that methicillin-resistant strains are also resistant to Augmentin, with susceptibility rates as low as 54.7% in multiresistant strains 2, 3
• Hospital-acquired staph infections where MRSA prevalence is high 3

What to Use Instead for MRSA

Current guidelines recommend completely different antibiotics for MRSA 7:

• Oral options: Trimethoprim-sulfamethoxazole, doxycycline, clindamycin (if local resistance <10%), or linezolid 7, 8
• IV options: Vancomycin, daptomycin, or linezolid 7

Key Caveat About Mixed Infections

In mixed skin infections containing both S. aureus and Streptococcus pyogenes, Augmentin has a unique advantage: it covers both organisms simultaneously 5. Animal model studies demonstrated that amoxicillin alone failed to eliminate streptococci when beta-lactamase-producing S. aureus was present (due to enzymatic inactivation), whereas Augmentin successfully treated both organisms 5. This makes Augmentin valuable for animal bites, human bites, and polymicrobial cellulitis where both organisms may coexist 6.

Bottom Line Algorithm

1. If MRSA is suspected or confirmed → Do NOT use Augmentin; use TMP-SMX, doxycycline, clindamycin, or vancomycin instead 7
2. If MSSA is confirmed and produces beta-lactamase → Augmentin is appropriate 1
3. If mixed infection with streptococci is suspected → Augmentin provides dual coverage 5
4. If susceptibility testing shows amoxicillin-susceptible MSSA → Use amoxicillin alone, not Augmentin 1