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

Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections

For most MRSA infections, treatment selection depends critically on infection site and severity, with incision and drainage being the primary intervention for abscesses, and antibiotic choice guided by whether the patient requires outpatient oral therapy or inpatient IV therapy.

Initial Management: Source Control First

• Incision and drainage is the primary and most critical treatment for cutaneous abscesses and must be performed whenever feasible 1, 2, 3
• Obtain cultures from purulent drainage before starting antibiotics to confirm MRSA and guide definitive therapy 4, 2, 3
• For simple abscesses or boils, incision and drainage alone may be adequate without antibiotics 1, 2
• Surgical debridement and elimination of infected materials (including removal of infected intravascular or prosthetic devices) is essential for complicated infections, as failure to remove infected materials is associated with higher relapse and mortality rates 1, 2, 3

Outpatient Oral Antibiotic Options for Non-Severe MRSA Infections

Add antibiotics to incision and drainage when any of the following are present: severe or extensive disease involving multiple sites, rapid progression with associated cellulitis, signs of systemic illness, immunosuppression, extremes of age, abscess in difficult-to-drain areas (face, hand, genitalia), or lack of response to drainage alone 1, 3

First-Line Oral Agents (5-10 days duration):

• Trimethoprim-sulfamethoxazole (TMP-SMX): 1-2 double-strength tablets orally twice daily (pediatric: 4-6 mg/kg/dose TMP component every 12 hours) 1, 4, 2, 3
• Doxycycline: 100 mg orally twice daily (or minocycline 100 mg orally twice daily) - avoid in children under 8 years 1, 4, 2, 3
• Clindamycin: 300-450 mg orally three times daily (pediatric: 10-13 mg/kg/dose every 6-8 hours, max 40 mg/kg/day) - only if local resistance rates are <10% 1, 2, 3
• Linezolid: 600 mg orally twice daily - highly effective but more expensive 1, 3, 5

Coverage Strategy for Purulent vs Non-Purulent Cellulitis:

• For purulent cellulitis (with purulent drainage/exudate but no drainable abscess): empirical therapy for CA-MRSA is recommended; empirical coverage for β-hemolytic streptococci is likely unnecessary 1
• For non-purulent cellulitis (no purulent drainage, no abscess): empirical therapy for β-hemolytic streptococci is recommended; add MRSA coverage only if patient fails β-lactam therapy or has systemic toxicity 1
• If dual coverage for both MRSA and β-hemolytic streptococci is desired: use clindamycin alone, OR combine TMP-SMX or tetracycline with a β-lactam (e.g., amoxicillin), OR use linezolid alone 1, 2

Inpatient IV Antibiotic Options for Complicated/Severe MRSA Infections

Hospitalize patients with: systemic toxicity, rapidly progressive infection, complicated skin and soft tissue infections (deeper infections, major abscesses, infected ulcers/burns), or bacteremia 1, 3

First-Line IV Agents for Complicated Skin/Soft Tissue Infections (7-14 days):

• Vancomycin: 15-20 mg/kg/dose IV every 8-12 hours (target trough 15-20 mcg/mL for serious infections) 1, 3
• Daptomycin: 4 mg/kg/dose IV once daily for complicated skin infections 1, 6
• Linezolid: 600 mg IV or PO twice daily 1, 3, 5
• Telavancin: 10 mg/kg/dose IV once daily 1
• Ceftaroline: 600 mg IV every 12 hours 7, 8

MRSA Bacteremia and Endocarditis

Uncomplicated Bacteremia (minimum 2 weeks):

Uncomplicated bacteremia is defined as: positive blood cultures with exclusion of endocarditis, no implanted prostheses, follow-up cultures at 2-4 days negative for MRSA, defervescence within 72 hours of effective therapy, and no metastatic infection sites 1

• Vancomycin IV (standard dosing) 1
• Daptomycin: 6 mg/kg/dose IV once daily (some experts recommend 8-10 mg/kg/dose for serious infections) 1, 6

Complicated Bacteremia (4-6 weeks depending on extent):

• Same agents as uncomplicated bacteremia but longer duration 1
• Do NOT add gentamicin to vancomycin - does not improve outcomes and increases toxicity 1
• Do NOT add rifampin to vancomycin - associated with longer bacteremia duration, hepatic adverse effects, drug interactions, and emergence of resistance 1

Infective Endocarditis (6 weeks):

• Vancomycin IV 1
• Daptomycin: 6 mg/kg/dose IV once daily (some experts recommend 8-10 mg/kg/dose) 1, 6
• Obtain echocardiography for all adult patients with MRSA bacteremia; transesophageal echocardiography (TEE) is preferred over transthoracic (TTE) 1
• Repeat blood cultures 2-4 days after initial positive cultures and as needed to document clearance 1, 4
• Consider valve replacement surgery if: large vegetation >10 mm, embolic event during first 2 weeks, severe valvular insufficiency, perforation/dehiscence, decompensated heart failure, perivalvular/myocardial abscess, new heart block, or persistent fevers/bacteremia 1

MRSA Urinary Tract Infections

• TMP-SMX: 1-2 double-strength tablets orally twice daily for 7-14 days for uncomplicated MRSA bacteriuria 4
• For complicated MRSA bacteriuria or concurrent bacteremia: treat for 2-4 weeks depending on clinical response 4
• Obtain blood cultures if systemic symptoms present to rule out concurrent bacteremia 4
• Follow-up urine cultures at 48-72 hours after initiating therapy to document clearance 4

Special Populations

Pediatric Patients:

• IV vancomycin is the preferred agent for serious MRSA infections in children 2
• Clindamycin can be used if patient is stable and local resistance rates are <10% 2
• Avoid tetracyclines in children under 8 years of age 4, 3
• For bacteremia in children 2-17 years: age-dependent daptomycin dosing (12 mg/kg for ages 2-6 years, 9 mg/kg for ages 7-11 years, 7 mg/kg for ages 12-17 years) showed 88% clinical success 6

Prevention of Recurrence

• Keep draining wounds covered with clean, dry bandages 4, 2, 3
• Maintain good personal hygiene with regular handwashing 4, 2, 3
• Consider decolonization with mupirocin (nasal) and chlorhexidine (body) for recurrent infections 2, 3
• Evaluate and potentially treat household contacts if recurrent infections persist 2

Critical Pitfalls to Avoid

• Never use β-lactam antibiotics alone for MRSA - the mechanism of methicillin resistance confers resistance to all β-lactams 2, 9
• Never use rifampin as monotherapy - associated with rapid resistance emergence 1, 2
• Do not use daptomycin for MRSA pneumonia - it is inactivated by pulmonary surfactant 7
• Failure to drain abscesses leads to treatment failure regardless of antibiotic choice 2
• Failure to remove infected prosthetic materials or intravascular devices is associated with higher relapse and mortality 1
• Clindamycin should only be used when local resistance rates are <10% - verify local antibiograms 1, 2, 3

Emerging Evidence on Vancomycin Alternatives

• Linezolid may be superior to vancomycin for MRSA infections overall, particularly for complicated skin/soft tissue infections and pneumonia, with improved clinical and microbiological success rates despite higher adverse reaction rates 10
• For MRSA pneumonia specifically, linezolid shows superiority over vancomycin and should be considered the preferred agent 11, 10
• Vancomycin elevations in MIC within the susceptible range are associated with treatment failure and mortality 8
• Daptomycin is the only antibiotic showing non-inferiority to vancomycin in MRSA bacteremia 11