What are the treatment differences between Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-susceptible Staphylococcus aureus (MSSA) infections?

Treatment Differences Between MRSA and MSSA Infections

For MSSA infections, a β-lactam antibiotic (such as oxacillin, nafcillin, or cefazolin) is the drug of choice, while vancomycin is the primary treatment for MRSA infections. 1

First-Line Therapy Options

For MSSA Infections:

• β-lactam antibiotics are preferred due to their superior efficacy compared to vancomycin 1, 2
• Options include:
  • Penicillinase-resistant penicillins (flucloxacillin, dicloxacillin) 2
  • First-generation cephalosporins (cefazolin, cephalothin, cephalexin) for less serious infections 2
  • Oxacillin, nafcillin, and cefazolin are preferred for proven MSSA infections 1

For MRSA Infections:

• Vancomycin is the first-line therapy for most serious MRSA infections 1, 3
  • Dosing: 15-20 mg/kg/dose IV every 8-12 hours, not exceeding 2g per dose 1
  • Target trough concentrations: 15-20 μg/mL for serious infections 1, 4
• Alternative agents for MRSA include:
  • Daptomycin: 6 mg/kg/dose IV once daily (not for pneumonia) 1, 5
  • Linezolid: 600 mg PO/IV twice daily 1, 6
  • Clindamycin: 600 mg every 8 hours (if strain is susceptible) 1

Treatment by Infection Type

Skin and Soft Tissue Infections

• MSSA: β-lactam antibiotics (flucloxacillin, dicloxacillin) or first-generation cephalosporins 2
• MRSA: Vancomycin IV, linezolid, clindamycin (if susceptible), or TMP-SMX 1, 3
• Duration: 5-10 days based on clinical response 3

Bacteremia and Endocarditis

• MSSA: Oxacillin or nafcillin 2
• MRSA:
  • Uncomplicated bacteremia: Vancomycin or daptomycin for at least 2 weeks 1
  • Complicated bacteremia: 4-6 weeks of therapy 1
  • Endocarditis: Vancomycin or daptomycin for 6 weeks 1
• Addition of gentamicin or rifampin to vancomycin is not recommended for MRSA bacteremia or native valve endocarditis 1

Pneumonia

• MSSA: β-lactam antibiotics (piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem) 1
• MRSA: Vancomycin or linezolid for 7-21 days, depending on infection extent 1
• Daptomycin should not be used for MRSA pneumonia due to inactivation by pulmonary surfactant 6

Osteomyelitis

• For both MSSA and MRSA: Surgical debridement and drainage of associated soft-tissue abscesses is essential 1
• MSSA: β-lactam antibiotics 2
• MRSA:
  • Parenteral options: Vancomycin or daptomycin 1
  • Oral options: TMP-SMX with rifampin, linezolid, or clindamycin 1
• Duration: Minimum 8-week course, with some experts suggesting additional 1-3 months of oral therapy 1

Pediatric Considerations

• MSSA: β-lactam antibiotics 2
• MRSA:
  • Vancomycin 15 mg/kg/dose IV every 6 hours 1
  • If patient is stable: Clindamycin 10-13 mg/kg/dose IV every 6-8 hours (if resistance rate is low) 1
  • Linezolid: 10 mg/kg/dose every 8 hours for children <12 years 1

Important Clinical Considerations

• Blood cultures should be obtained 2-4 days after initial positive cultures to document clearance of bacteremia in MRSA infections 1
• Echocardiography is recommended for all adult patients with MRSA bacteremia 1
• Higher vancomycin trough levels (≥15 mg/L) are associated with better outcomes in severe MRSA infections but also with increased nephrotoxicity 4
• No antagonism has been observed between vancomycin and β-lactams when used in combination for MSSA 7
• Newer agents (linezolid, daptomycin, ceftaroline) are now recommended as co-first-line options alongside vancomycin for certain MRSA infections 8

Common Pitfalls and Caveats

• Using vancomycin for MSSA when a β-lactam is available (β-lactams are more effective against MSSA) 2
• Using daptomycin for MRSA pneumonia (contraindicated due to inactivation by pulmonary surfactant) 6
• Inadequate vancomycin dosing leading to subtherapeutic levels and treatment failure 4
• Failure to obtain follow-up blood cultures to document clearance of bacteremia 1
• Inadequate source control (drainage of abscesses, removal of infected devices) 1