Does Unasyn (Ampicillin/Sulbactam) cover Methicillin-resistant Staphylococcus aureus (MRSA)?

Does Unasyn Cover MRSA?

No, Unasyn (ampicillin/sulbactam) does not provide coverage against Methicillin-resistant Staphylococcus aureus (MRSA). 1, 2

Unasyn Coverage and Limitations

Unasyn is a combination of ampicillin (a beta-lactam antibiotic) and sulbactam (a beta-lactamase inhibitor) that provides:

• Effective coverage against gram-positive organisms (non-MRSA Staphylococcus aureus, streptococci)
• Coverage of many gram-negative bacteria (E. coli, Proteus spp.)
• Activity against anaerobes including Bacteroides fragilis
• Protection against certain beta-lactamase producing organisms 1, 3

However, Unasyn lacks activity against MRSA because:

• MRSA resistance is primarily mediated by the mecA gene, which produces PBP2a (an altered penicillin-binding protein)
• PBP2a has low affinity for beta-lactam antibiotics, including ampicillin/sulbactam
• The beta-lactamase inhibitor (sulbactam) only overcomes resistance due to beta-lactamase production, not the PBP2a-mediated resistance mechanism 4

Appropriate Antibiotics for MRSA Coverage

When MRSA coverage is needed, the following agents should be used instead:

Oral options:

• Trimethoprim-sulfamethoxazole (TMP-SMX): 1-2 double-strength tablets twice daily
• Doxycycline: 100 mg twice daily
• Minocycline: 200 mg loading dose, then 100 mg twice daily
• Clindamycin: 300-450 mg four times daily (if local resistance rates are low)
• Linezolid: 600 mg twice daily (for severe cases) 2

Intravenous options:

• Vancomycin: 30-60 mg/kg/day in 2-4 divided doses (first-line for serious MRSA infections)
• Daptomycin: 4-6 mg/kg once daily
• Linezolid: 600 mg twice daily
• Teicoplanin: 6-12 mg/kg/dose q12h for three doses, then once daily 2

Clinical Decision-Making for Antibiotic Selection

When deciding whether to provide MRSA coverage:

1. Assess MRSA risk factors:

   • Previous MRSA infection or colonization within the past year
   • High local prevalence of MRSA (>50% for mild infections, >30% for moderate infections)
   • Severity of infection where treatment failure would pose significant risk 1

2. Consider infection type:

   • For complicated skin/soft tissue infections or diabetic foot infections where MRSA is suspected, empiric MRSA coverage is recommended
   • For intra-abdominal infections with suspected MRSA involvement, vancomycin may need to be added to standard regimens 1

3. Obtain cultures when possible:

   • Adjust therapy based on culture results
   • For bone infections, obtain bone specimen when MRSA is suspected 1

Common Pitfalls to Avoid

• Pitfall #1: Assuming beta-lactam/beta-lactamase inhibitor combinations like Unasyn will cover MRSA. They will not, as MRSA resistance is primarily due to PBP2a, not beta-lactamase production.

• Pitfall #2: Relying on older studies suggesting potential activity of ampicillin/sulbactam against some MRSA strains. Current clinical guidelines clearly indicate that Unasyn is not appropriate for MRSA treatment 1, 2.

• Pitfall #3: Failing to consider local resistance patterns when selecting empiric therapy. Local antibiograms should guide initial treatment choices.

• Pitfall #4: Delaying appropriate MRSA coverage in high-risk patients or severe infections while awaiting culture results, which could lead to treatment failure and worse outcomes 1.