What is the recommended treatment for Methicillin-resistant Staphylococcus aureus (MRSA) infections?

Treatment of MRSA Infections

IV vancomycin 15-20 mg/kg/dose (actual body weight) every 8-12 hours, not to exceed 2 g per dose, is the first-line treatment for most serious MRSA infections in adults with normal renal function, with target trough concentrations of 15-20 µg/mL for bacteremia, endocarditis, osteomyelitis, meningitis, pneumonia, and severe skin/soft tissue infections. 1

Vancomycin Dosing and Monitoring

Standard Dosing

• For serious infections (bacteremia, endocarditis, osteomyelitis, meningitis, pneumonia, severe SSTI): Vancomycin 15-20 mg/kg/dose IV every 8-12 hours based on actual body weight, targeting trough concentrations of 15-20 µg/mL 1
• For uncomplicated SSTI in non-obese patients with normal renal function: Traditional doses of 1 g IV every 12 hours are adequate without trough monitoring 1
• Loading dose for critically ill patients: Consider 25-30 mg/kg (actual body weight) for sepsis, meningitis, pneumonia, or endocarditis, with prolonged infusion time (2 hours) and antihistamine premedication to reduce red man syndrome risk 1

Therapeutic Drug Monitoring

• Trough monitoring is mandatory for: Serious infections, morbidly obese patients, renal dysfunction (including dialysis), or fluctuating volumes of distribution 1
• Obtain trough levels: Prior to the fourth or fifth dose at steady state 1
• Peak monitoring is not recommended 1

MIC-Based Decision Making

• For vancomycin MIC <2 µg/mL: Continue vancomycin if clinical and microbiologic response is adequate; switch to alternative if no response despite adequate source control 1
• For vancomycin MIC >2 µg/mL (VISA/VRSA): Use an alternative agent immediately 1

Alternative First-Line Agents

Linezolid

• Dosing: 600 mg IV or PO every 12 hours 1
• Preferred for: MRSA pneumonia due to superior lung tissue penetration 2, 3
• Equivalent efficacy to vancomycin for complicated skin/soft tissue infections with cure rate of 88.6% vs 66.9% for vancomycin (p<0.001) 2, 3
• Acceptable for: 4-6 weeks of therapy for bacteremia and endocarditis, though data are more limited than vancomycin 2
• Advantage: No therapeutic drug monitoring required 2
• Caution: Prolonged use increases risk of hematologic adverse effects (thrombocytopenia, anemia) 2

Daptomycin

• Dosing for bacteremia/endocarditis: 6 mg/kg IV once daily (some experts recommend 8-10 mg/kg/day) 1, 4
• Dosing for osteomyelitis: 6 mg/kg IV once daily 1
• Contraindication: Do NOT use for pneumonia (inactivated by pulmonary surfactant) 5, 6
• Advantage: Once-daily dosing, no therapeutic drug monitoring 6
• Efficacy: Non-inferior to vancomycin for S. aureus bacteremia/endocarditis with success rate of 44.2% vs 41.7% 4

Infection-Specific Recommendations

Bacteremia and Endocarditis

• Uncomplicated bacteremia: Vancomycin or daptomycin 6 mg/kg IV daily for at least 2 weeks 1
• Complicated bacteremia: 4-6 weeks of therapy depending on extent of infection 1
• Infective endocarditis: Vancomycin or daptomycin 6 mg/kg IV daily (consider 8-10 mg/kg/day) for 6 weeks 1
• Do NOT add gentamicin or rifampin to vancomycin for native valve endocarditis 1
• Mandatory: Obtain follow-up blood cultures 2-4 days after initial positive cultures to document clearance 1
• Mandatory: Perform echocardiography (preferably transesophageal) for all adult patients with bacteremia 1

Pneumonia

• First-line: Linezolid 600 mg IV/PO every 12 hours (superior to vancomycin) 2, 3
• Alternative: Vancomycin with target trough 15-20 µg/mL 1
• Do NOT use daptomycin for pneumonia 5, 6
• If empyema present: Antimicrobial therapy PLUS drainage procedures 1

Osteomyelitis

• Surgical debridement is mandatory whenever feasible 1
• Parenteral options: Vancomycin or daptomycin 6 mg/kg IV daily 1
• Oral options: TMP-SMX 4 mg/kg (TMP component) twice daily + rifampin 600 mg daily, linezolid 600 mg twice daily, or clindamycin 600 mg every 8 hours 1
• Duration: Minimum 8 weeks; consider additional 1-3 months of oral rifampin-based combination therapy 1
• Rifampin addition: Consider adding rifampin 600 mg daily or 300-450 mg twice daily AFTER bacteremia clearance 1

CNS Infections (Meningitis, Brain Abscess, Epidural Abscess)

• Meningitis: Vancomycin IV for 2 weeks; consider adding rifampin 600 mg daily or 300-450 mg twice daily 1
• Brain abscess/epidural abscess: Vancomycin IV for 4-6 weeks; consider adding rifampin 1
• Neurosurgical evaluation mandatory for incision and drainage 1
• Alternatives: Linezolid 600 mg IV/PO every 12 hours or TMP-SMX 5 mg/kg/dose IV every 8-12 hours 1
• CNS shunt infection: Remove shunt; do not replace until CSF cultures repeatedly negative 1

Skin and Soft Tissue Infections

• Uncomplicated SSTI: Vancomycin 1 g IV every 12 hours (no trough monitoring needed if normal renal function, not obese) 1
• Severe SSTI (necrotizing fasciitis): Vancomycin with target trough 15-20 µg/mL 1
• Alternative: Linezolid 600 mg IV/PO every 12 hours 2, 3

Management of Vancomycin Treatment Failures

Persistent Bacteremia

• First step: Search for and remove foci of infection, perform surgical drainage/debridement 1
• High-dose daptomycin: 10 mg/kg/day IV in combination with another agent (gentamicin 1 mg/kg IV every 8 hours, rifampin 600 mg daily or 300-450 mg twice daily, linezolid 600 mg twice daily, TMP-SMX 5 mg/kg IV twice daily, or beta-lactam) 1
• If reduced susceptibility to both vancomycin and daptomycin: Consider quinupristin-dalfopristin 7.5 mg/kg IV every 8 hours, TMP-SMX 5 mg/kg IV twice daily, linezolid 600 mg twice daily, or telavancin 10 mg/kg IV daily (as single agent or combination) 1

Pediatric Considerations

Dosing

• Vancomycin: 15 mg/kg/dose IV every 6 hours for serious/invasive disease 1
• Target trough 15-20 µg/mL should be considered for serious infections (bacteremia, endocarditis, osteomyelitis, meningitis, pneumonia, severe SSTI) 1
• Clindamycin: 10-13 mg/kg/dose IV every 6-8 hours (40 mg/kg/day total) if clindamycin resistance rate <10% and patient is stable without ongoing bacteremia 1
• Linezolid: 10 mg/kg/dose every 8 hours for children <12 years; 600 mg every 12 hours for children ≥12 years 1, 3

Neonates

• Mild localized disease: Topical mupirocin may be adequate in full-term neonates 1
• Extensive disease or premature/very low birthweight: Vancomycin or clindamycin IV until bacteremia excluded 1

Common Pitfalls to Avoid

• Do NOT use traditional 1 g every 12 hours dosing for critically ill trauma patients with MRSA pneumonia—doses of at least 1 g every 8 hours are needed to achieve target troughs 7
• Do NOT use daptomycin for pneumonia—it is inactivated by pulmonary surfactant 5, 6
• Do NOT use clindamycin empirically without susceptibility testing due to variable regional resistance rates 2
• Do NOT use fluoroquinolones as monotherapy—resistance emerges rapidly even against susceptible CA-MRSA strains 2
• Do NOT forget source control—antimicrobial therapy alone is insufficient without drainage of abscesses, debridement of infected tissue, or removal of infected devices 2
• Do NOT add gentamicin or rifampin to vancomycin for native valve endocarditis or uncomplicated bacteremia 1
• Do NOT use protein synthesis inhibitors (clindamycin, linezolid) or IVIG routinely as adjunctive therapy for invasive MRSA disease; consider only in selected scenarios like necrotizing pneumonia or severe sepsis 1