What are the first-line antibiotics for Methicillin-Resistant Staphylococcus Aureus (MRSA) and Methicillin-Sensitive Staphylococcus Aureus (MSSA) infections?

First-Line Antibiotics for MRSA and MSSA Infections

MSSA (Methicillin-Sensitive Staphylococcus Aureus)

For MSSA infections, β-lactam antibiotics—specifically nafcillin, oxacillin, or cefazolin—are the first-line agents and are superior to vancomycin. 1

Parenteral (IV) Therapy for MSSA

• Nafcillin or oxacillin 1-2 g IV every 4 hours is the preferred treatment for severe MSSA infections 2
• Cefazolin 1-2 g IV every 8 hours is an excellent alternative with better tissue penetration and less nephrotoxicity than vancomycin 2
• For penicillin-allergic patients (except those with immediate hypersensitivity reactions like urticaria, angioedema, or anaphylaxis), cefazolin remains appropriate 3
• Vancomycin 15-20 mg/kg IV every 8-12 hours should be reserved only for patients with immediate-type penicillin hypersensitivity 2

Oral Therapy for MSSA

• Dicloxacillin 500 mg orally four times daily is the oral agent of choice 3
• Cephalexin 500 mg orally four times daily is the preferred alternative for penicillin-allergic patients (pediatric dosing: 25 mg/kg/day in 4 divided doses) 3
• Clindamycin 300-450 mg orally three times daily is effective for penicillin-allergic patients if local resistance rates are <10% (pediatric: 10-20 mg/kg/day in 3 divided doses) 3

When to Use Oral vs. IV Therapy for MSSA

Avoid oral therapy and use parenteral antibiotics when the patient has: 3

• Severe or extensive disease involving multiple sites
• Rapid progression with associated cellulitis
• Signs of systemic illness (fever, hypotension, altered mental status)
• Immunosuppression or significant comorbidities
• Associated septic phlebitis

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MRSA (Methicillin-Resistant Staphylococcus Aureus)

For MRSA infections, vancomycin 15-20 mg/kg/dose IV every 8-12 hours (not exceeding 2g per dose) is the first-line therapy, with target trough concentrations of 15-20 μg/mL for serious infections. 1

Parenteral (IV) Therapy for MRSA

• Vancomycin remains the standard first-line agent for most MRSA infections, though newer alternatives exist 1, 4
• Daptomycin 6 mg/kg IV once daily is the only antibiotic that has shown non-inferiority to vancomycin in MRSA bacteremia and is FDA-approved for this indication 5, 6
• Linezolid 600 mg PO/IV twice daily has shown superiority to vancomycin specifically in hospital-acquired MRSA pneumonia and is an important option for proven MRSA lung infections 7, 6, 8
• For pediatric MRSA infections, vancomycin is dosed at 15 mg/kg/dose IV every 6 hours 1

Oral Therapy for MRSA

For less serious MRSA infections (particularly skin and soft tissue infections where bactericidal activity is not absolutely required):

• Clindamycin 600-900 mg IV every 8 hours (or 300-450 mg orally every 6-8 hours) can be used if local resistance rates are <10% 7, 2
• Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 double-strength tablets twice daily is effective for non-multiresistant community-acquired MRSA skin infections, though less effective against streptococci 2, 9
• Linezolid 600 mg orally twice daily can be used for oral step-down therapy 7
• Doxycycline or minocycline 100 mg orally twice daily may be used but are contraindicated in children <8 years 3

Infection-Specific MRSA Treatment Durations

The duration of therapy varies significantly by infection type: 1

• Uncomplicated bacteremia: 2 weeks minimum
• Complicated bacteremia: 4-6 weeks
• Endocarditis: 6 weeks
• Pneumonia: 7-21 days depending on extent
• Osteomyelitis: Minimum 8 weeks (with surgical debridement)
• Skin/soft tissue infections with adequate drainage: 5-10 days 2

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Critical Management Principles

For All Staphylococcal Infections

• Obtain blood cultures before starting antibiotics to guide definitive therapy 2
• For MRSA bacteremia, obtain follow-up blood cultures 2-4 days after initial positive cultures to document clearance 1
• Echocardiography (including TEE) is recommended for all adult patients with MRSA bacteremia 1
• Adequate source control is essential—failure to drain abscesses or remove infected devices is a common cause of treatment failure 1, 2

Common Pitfalls to Avoid

• Never use vancomycin for MSSA when β-lactams are available—β-lactams are superior in efficacy 1, 9
• Failure to obtain follow-up blood cultures to document clearance of bacteremia 1
• Inadequate surgical debridement or source control 1, 2
• Stopping antibiotics prematurely, especially if fever or leukocytosis persists 2
• Not considering metastatic foci of infection in patients with persistent bacteremia 2

Decolonization for Recurrent Infections

For recurrent MSSA or MRSA abscesses, consider a 5-day decolonization regimen with intranasal mupirocin and chlorhexidine washes 2