What is the recommended treatment for Methicillin-Sensitive Staphylococcus aureus (MSSA) bacteremia?

Treatment of Methicillin-Sensitive Staphylococcus aureus (MSSA) Bacteremia

For MSSA bacteremia, an antistaphylococcal penicillin (nafcillin or oxacillin) or cefazolin is the recommended first-line treatment, with both options showing similar mortality outcomes. 1

First-Line Treatment Options

Antistaphylococcal Penicillins (ASPs)

• Nafcillin or oxacillin: Traditional first-line agents for MSSA bacteremia
  • Dosing: Nafcillin 2g IV every 4 hours (adult dosing)
  • Duration:
    • Uncomplicated bacteremia: at least 2 weeks
    • Complicated bacteremia: 4-6 weeks
    • Infective endocarditis: 6 weeks

Cefazolin

• Equally effective alternative to ASPs with similar mortality outcomes 1
• Potential advantages over ASPs:
  • Better tolerability
  • Lower rates of adverse drug reactions
  • More convenient dosing regimen
  • Dosing: 2g IV every 8 hours (standard adult dosing)

Treatment Algorithm

1. Obtain blood cultures before starting antibiotics
2. Initiate empiric therapy while awaiting culture results
3. Once MSSA is confirmed:
   • Switch to either nafcillin/oxacillin or cefazolin
   • Avoid vancomycin for MSSA (inferior outcomes compared to β-lactams) 2
4. Assess for complications:
   • Perform echocardiography (TEE preferred over TTE in adults) 2
   • Identify and eliminate source of infection (remove infected devices, drain abscesses) 2
5. Monitor response:
   • Obtain follow-up blood cultures 2-4 days after initial positive cultures 2
   • Document clearance of bacteremia

Treatment Duration

• Uncomplicated bacteremia: Minimum 2 weeks 2

  • Defined as: exclusion of endocarditis, no implanted prostheses, negative follow-up blood cultures at 2-4 days, defervescence within 72 hours, no metastatic infection

• Complicated bacteremia: 4-6 weeks 2

  • Defined as not meeting criteria for uncomplicated bacteremia

• Infective endocarditis: 6 weeks 2

Special Considerations

Brain Abscess

• Nafcillin is preferred over cefazolin due to better blood-brain barrier penetration 2

Cefazolin Inoculum Effect

• Some MSSA isolates show increased MICs at high bacterial inocula
• Recent data suggests this may not significantly impact clinical outcomes 3
• Adequate source control and aggressive cefazolin dosing may mitigate this effect 4

Alternative Agents (for patients with severe β-lactam allergies)

• Vancomycin: Less effective than β-lactams for MSSA but can be used if necessary 2
• Daptomycin: Consider in patients who cannot tolerate first-line therapy 5

Common Pitfalls to Avoid

1. Using vancomycin when β-lactams can be used: Vancomycin has been consistently shown to be less effective than β-lactams for MSSA bacteremia 2

2. Adding gentamicin to therapy: Addition of gentamicin to β-lactams is not recommended as it increases nephrotoxicity without improving outcomes 2

3. Adding rifampin to therapy: Addition of rifampin is not recommended for native valve endocarditis or uncomplicated bacteremia 2

4. Using once-daily regimens: Once-daily antibiotics (like ceftriaxone) have insufficient evidence to support their use as primary therapy for MSSA bacteremia 5

5. Inadequate source control: Failure to remove infected devices or drain abscesses is associated with higher relapse and mortality rates 2

6. Insufficient follow-up: Failure to obtain follow-up blood cultures to document clearance of bacteremia 2