Recommended Treatment for Methicillin-Sensitive Staphylococcus Aureus (MSSA) Coverage
For proven MSSA infections, oxacillin, nafcillin, or cefazolin are the preferred first-line treatments due to their superior efficacy and targeted spectrum of activity. 1
First-Line Treatment Options for Proven MSSA
- Antistaphylococcal penicillins: Oxacillin or nafcillin 2g IV every 4-6 hours (dosage may vary based on infection severity) 2
- First-generation cephalosporins: Cefazolin 0.5-1g IV every 8 hours (preferred alternative to antistaphylococcal penicillins) 1, 3
- For less severe infections: Cephalexin 500mg PO every 6 hours (oral option for step-down therapy) 1
Empiric Treatment Options When MSSA is Suspected
When empiric treatment for MSSA is needed (before culture results are available):
- Piperacillin-tazobactam 4.5g IV every 6 hours 1
- Cefepime 2g IV every 8 hours 1
- Levofloxacin 750mg IV daily 1
- Imipenem 500mg IV every 6 hours 1
- Meropenem 1g IV every 8 hours 1
Clinical Considerations
Infection Type and Severity
- Severe infections: Higher doses and longer duration (typically 14 days minimum for severe staphylococcal infections) 2
- Bacteremia and endocarditis: Antistaphylococcal penicillins or cefazolin are strongly preferred 3, 4
- Osteomyelitis: Requires 4-6 weeks of therapy; consider adding rifampin for biofilm penetration 1
- Skin and soft tissue infections: Shorter courses (7-14 days) may be adequate 1
Comparative Effectiveness and Tolerability
- Cefazolin has similar clinical efficacy to oxacillin/nafcillin for MSSA bacteremia, including deep-seated infections 3, 4
- Cefazolin has significantly fewer adverse events compared to nafcillin (6.7% vs 33.8% premature discontinuation rate) 5
- Common adverse events with nafcillin include rash (13.9%), renal dysfunction (11.4%), and liver function abnormalities (8.1%) 5
- Piperacillin-tazobactam may be associated with higher mortality compared to nafcillin/oxacillin/cefazolin when used as monotherapy for MSSA bacteremia 4
Special Considerations
- For patients with penicillin allergy: Cefazolin is preferred unless the patient has immediate hypersensitivity reaction history (urticaria, angioedema, bronchospasm, anaphylaxis) 6
- For patients with severe penicillin allergy: Consider vancomycin or clindamycin 1
- Oxacillin MIC levels (≥1 μg/mL vs <1 μg/mL) do not appear to affect treatment outcomes with either antistaphylococcal penicillins or cefazolin 7
Duration of Therapy
- Uncomplicated MSSA infections: 7-14 days 2
- Bacteremia: Minimum 14 days 2
- Endocarditis: 4-6 weeks 1
- Osteomyelitis: 4-6 weeks 1
- Continue therapy for at least 48 hours after the patient becomes afebrile, asymptomatic, and cultures are negative 2
Common Pitfalls to Avoid
- Inadequate dosing or duration of therapy, particularly for deep-seated infections 2
- Using broad-spectrum agents (like piperacillin-tazobactam) as definitive therapy when narrower-spectrum options are available 4
- Failure to transition from empiric to targeted therapy once MSSA is confirmed 1
- Not monitoring for adverse effects, particularly with antistaphylococcal penicillins 5
- Inadequate surgical debridement when indicated (particularly for abscesses, osteomyelitis, or necrotizing infections) 1