What are the recommended antibiotics for treating Methicillin-Sensitive Staphylococcus aureus (MSSA) bacteremia?

Recommended Antibiotics for MSSA Bacteremia

For treatment of Methicillin-Sensitive Staphylococcus aureus (MSSA) bacteremia, antistaphylococcal beta-lactams including nafcillin, oxacillin, or cefazolin are the preferred first-line agents due to their superior efficacy and outcomes. 1, 2

First-Line Treatment Options

• Antistaphylococcal penicillins (nafcillin or oxacillin) are preferred first-line agents for MSSA bacteremia due to their excellent efficacy and established clinical outcomes 1
• Cefazolin is an equally effective alternative to nafcillin/oxacillin with comparable mortality outcomes 3
• Standard duration of therapy for uncomplicated MSSA bacteremia is typically 2 weeks, while complicated cases (endocarditis, metastatic infections) require at least 4-6 weeks of treatment 1
• Gentamicin should NOT be used for treatment of MSSA bacteremia as it provides no additional benefit and increases toxicity 1

Treatment in Penicillin-Allergic Patients

• For patients with non-anaphylactic penicillin allergy (e.g., simple rash), cefazolin is a reasonable alternative 1
• For patients with true immediate-type hypersensitivity to penicillins, consider desensitization protocols rather than alternative agents when possible 1
• In cases where beta-lactams cannot be used, vancomycin or daptomycin may be considered as alternative agents 1, 4

Special Considerations

• For MSSA bacteremia with brain abscess, nafcillin is preferred over cefazolin due to better CNS penetration 1
• Piperacillin-tazobactam should not be used as monotherapy for definitive treatment of MSSA bacteremia, as it is associated with higher mortality compared to antistaphylococcal beta-lactams 3
• Once-daily regimens like ceftriaxone lack sufficient evidence for routine use in MSSA bacteremia, though ceftriaxone may be considered for completion therapy in certain cases like osteomyelitis 5

Treatment Algorithm

1. Empiric therapy (before susceptibility results):

   • If MRSA risk factors present: vancomycin or daptomycin 4
   • If polymicrobial infection suspected: piperacillin-tazobactam plus vancomycin 2

2. Definitive therapy (after confirming MSSA):

   • First choice: Nafcillin or oxacillin 1, 2
   • Alternative: Cefazolin (similar efficacy to nafcillin/oxacillin) 3
   • For penicillin allergy: Follow allergy severity-based approach as outlined above 1

3. Duration of therapy:

   • Uncomplicated bacteremia: 2 weeks 4
   • Complicated bacteremia (endocarditis, metastatic infections): At least 6 weeks 1

Clinical Pearls and Pitfalls

• The oxacillin MIC value (≥1 μg/mL vs <1 μg/mL) does not appear to affect treatment outcomes with either antistaphylococcal penicillins or cefazolin 6
• Cephalotin and dicloxacillin have shown similar efficacy for MSSA bacteremia in settings where first-line agents are unavailable 7
• Despite in vitro activity against MSSA, fluoroquinolones should not be routinely used as first-line therapy due to limited clinical evidence and risk of resistance development 3
• Always obtain follow-up blood cultures to document clearance of bacteremia, as persistent bacteremia (≥48 hours) is associated with significantly higher mortality (39% at 90 days) 4