What antibiotic changes should be made from Vancomycin (vancomycin) when a culture is identified as Methicillin-Susceptible Staphylococcus aureus (MSSA) instead of Methicillin-Resistant Staphylococcus aureus (MRSA)?

Antibiotic Change from Vancomycin for MSSA

When cultures confirm MSSA instead of MRSA, you must immediately switch from vancomycin to an antistaphylococcal penicillin (nafcillin or oxacillin) or cefazolin, as beta-lactams demonstrate superior outcomes and lower mortality compared to vancomycin for MSSA infections. 1, 2

Primary Antibiotic Choices for MSSA

Nafcillin or oxacillin is the preferred first-line agent for MSSA bacteremia and serious infections:

• Dosing: 2 g IV every 4 hours for severe infections 1, 3
• Duration: 6 weeks for uncomplicated left-sided endocarditis; at least 6 weeks for complicated infections 1
• Superior to vancomycin for all MSSA infections based on meta-analyses showing better bacteremic clearance and mortality outcomes 1, 2

Cefazolin is an acceptable alternative:

• Dosing: 1-2 g IV every 8 hours 4, 2
• Use in patients with non-severe (non-anaphylactoid) penicillin allergies 1, 3
• Many experts use cefazolin routinely due to tolerability, cost, and ease of outpatient administration 1

Critical Exception: CNS/Spinal Infections

For brain abscess or epidural abscess complicating MSSA bacteremia, nafcillin must be used instead of cefazolin:

• Nafcillin has superior blood-brain barrier penetration compared to cefazolin 1, 5, 3
• Vancomycin is the only acceptable alternative if nafcillin cannot be tolerated 1, 5
• This is a Class I recommendation from the American Heart Association 1

What NOT to Do

Do not add gentamicin to beta-lactam therapy:

• Gentamicin provides no mortality benefit or reduction in cardiac complications 1, 5
• Significantly increases nephrotoxicity risk 5
• This is a Class III recommendation (should not be done) for both native valve endocarditis and MSSA bacteremia 1

Do not continue vancomycin once MSSA is confirmed:

• Vancomycin is associated with poorer outcomes for MSSA infections compared to beta-lactams 1
• The only exceptions are true anaphylactoid-type beta-lactam allergy or CNS infections where nafcillin cannot be used 1

Algorithm for Beta-Lactam Allergy

If patient reports penicillin allergy, stratify by reaction type:

• Non-severe reaction (simple rash): Use cefazolin 1-2 g IV every 8 hours 1, 4
• Severe/anaphylactoid reaction (urticaria, angioedema, bronchospasm):
  • Consider beta-lactam desensitization protocol 1
  • If desensitization not feasible, use vancomycin 15-20 mg/kg IV every 8-12 hours 1, 4
  • For CNS infections with true beta-lactam allergy, vancomycin is the only option 1, 5

When to Consider Alternative Agents

If bacteremia persists beyond 48-72 hours despite adequate source control:

• Switch to high-dose daptomycin 8-10 mg/kg IV daily 5
• Obtain infectious diseases consultation for daptomycin dosing decisions 1, 5
• Daptomycin is a reasonable alternative to vancomycin for left-sided endocarditis caused by MRSA, but data for MSSA are limited 1

Common Pitfalls to Avoid

Continuing vancomycin for MSSA "because the patient is doing well":

• This approach increases mortality risk compared to switching to beta-lactams 1, 2
• The superiority of beta-lactams over vancomycin for MSSA is well-established 1

Using cefazolin for CNS/spinal infections:

• Results in inadequate CNS penetration and treatment failure 5, 3
• Always use nafcillin for these infections unless contraindicated 1, 5

Stopping antibiotics prematurely:

• Complicated MSSA bacteremia requires 4-6 weeks of therapy 5, 3
• Endocarditis requires minimum 6 weeks from first negative blood culture 1, 5