For a patient with a history of Methicillin-resistant Staphylococcus aureus (MRSA) infection who has failed two rounds of Bactrim (trimethoprim/sulfamethoxazole), would you consider adding Augmentin (amoxicillin/clavulanate) to linezolid for coverage of gram-positive organisms like Streptococcus?

Adding Augmentin to Linezolid for Gram-Positive Coverage in MRSA Patients

No, you should not add Augmentin (amoxicillin/clavulanate) to linezolid for MRSA coverage, as beta-lactam antibiotics like Augmentin have no activity against MRSA and provide no additional benefit. 1

Why Augmentin is Inappropriate for MRSA

• MRSA resistance is conferred by the mecA gene encoding PBP2a, a penicillin-binding protein with significantly lower affinity for all beta-lactams, including amoxicillin/clavulanate 2
• Beta-lactam antibiotics alone are inadequate for MRSA coverage and should not be used 1
• Adding Augmentin to linezolid would only increase antibiotic exposure, cost, and potential adverse effects without improving MRSA coverage 2

When Combination Therapy IS Appropriate

If you need coverage for both MRSA AND beta-hemolytic streptococci (Group A Strep), you have two evidence-based options:

Option 1: Switch to Clindamycin Monotherapy

• Clindamycin 300-450 mg orally three times daily provides coverage for both MRSA and streptococci as a single agent 2, 3
• Critical caveat: Only use clindamycin if local MRSA resistance rates are <10% 2, 4
• Must perform D-test to rule out inducible clindamycin resistance, as approximately 50% of MRSA strains may have inducible or constitutive resistance 4
• Higher risk of Clostridioides difficile infection compared to other oral agents 4

Option 2: Combine Linezolid with a Beta-Lactam

• Continue linezolid 600 mg orally twice daily for MRSA coverage 2, 1
• Add a beta-lactam specifically for streptococcal coverage: penicillin, cephalexin, or amoxicillin (NOT Augmentin, as the clavulanate adds nothing) 2
• This combination is recommended when dual coverage is needed and clindamycin cannot be used 2

Why Linezolid Alone May Be Insufficient After Bactrim Failure

• Linezolid is bacteriostatic against staphylococci (not bactericidal), which may be problematic in treatment failures 5
• Current guidelines do not recommend linezolid as first-line treatment for MRSA bacteremia due to lack of prospective RCT data 2
• In your patient with two failed courses of Bactrim, consider whether the infection source has been adequately controlled (abscess drainage, foreign body removal) 1

Better Alternatives to Consider

For a patient failing oral therapy with recurrent MRSA infection:

• Daptomycin 4-6 mg/kg IV once daily is bactericidal against MRSA and FDA-approved for MRSA bacteremia 2, 1
• Vancomycin 15-20 mg/kg IV every 8-12 hours remains standard of care for serious MRSA infections 2, 3
• Consider whether surgical source control (drainage, debridement) has been adequate, as antibiotics alone often fail without proper source control 1, 3

Treatment Duration and Monitoring

• For uncomplicated MRSA skin infections: 5-10 days of therapy 1, 3
• For complicated infections or bacteremia: minimum 2 weeks for uncomplicated bacteremia, 4-6 weeks for complicated bacteremia 1
• Reassess within 48-72 hours to ensure clinical response 3
• If using linezolid for >2 weeks, monitor complete blood counts weekly due to risk of myelosuppression 5

Key Clinical Pitfall to Avoid

The most common error is adding unnecessary antibiotics without addressing the underlying source of infection. In patients failing multiple antibiotic courses, the priority is identifying and eliminating the infection source (undrained abscess, retained foreign body, prosthetic material) rather than adding more antibiotics 2, 1