What is the best oral antimicrobial choice for a skin and soft tissue infection caused by Methicillin-resistant Staphylococcus aureus (MRSA)?

Oral Antimicrobial Treatment for MRSA Skin and Soft Tissue Infections

For MRSA skin and soft tissue infections requiring oral therapy, trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 double-strength tablets twice daily, doxycycline 100 mg twice daily, or clindamycin 300-450 mg three times daily are the recommended first-line oral options, with TMP-SMX and doxycycline preferred due to lower cost and comparable efficacy to more expensive alternatives like linezolid. 1

First-Line Oral Agents for MRSA SSTI

TMP-SMX (Trimethoprim-Sulfamethoxazole)

• Adult dosing: 1-2 double-strength tablets orally twice daily 1
• Pediatric dosing: Trimethoprim 4-6 mg/kg/dose, sulfamethoxazole 20-30 mg/kg/dose orally every 12 hours 1
• Key advantages: Bactericidal activity and demonstrated effectiveness in randomized trials 1
• Important caveat: Pregnancy category C/D; contraindicated in third trimester pregnancy and children <2 months of age 1
• Limitation: Activity against β-hemolytic streptococci is not well-defined, so consider adding a β-lactam if streptococcal coverage is needed 1

Doxycycline

• Adult dosing: 100 mg orally twice daily 1
• Pediatric dosing: <45 kg: 2 mg/kg/dose orally every 12 hours 1
• Key advantages: Good in vitro activity against CA-MRSA with proven clinical effectiveness 1
• Important caveat: Contraindicated in children <8 years of age and pregnancy category D 1
• Limitation: Like TMP-SMX, activity against β-hemolytic streptococci is not well-defined 1

Clindamycin

• Adult dosing: 300-450 mg orally three times daily 1
• Pediatric dosing: 10-13 mg/kg/dose orally every 6-8 hours, not to exceed 40 mg/kg/day 1
• Key advantage: Active against both MRSA and β-hemolytic streptococci, making it useful for nonpurulent cellulitis 1
• Critical caveat: Inducible clindamycin resistance should preclude use in more serious infections; may be acceptable for mild infections despite resistance 1
• Warning: Clostridium difficile-associated disease may occur more frequently compared with other oral agents 1

Minocycline

• Adult dosing: 200 mg loading dose, then 100 mg orally twice daily 1
• Pediatric dosing: 4 mg/kg loading dose, then 2 mg/kg/dose orally every 12 hours 1
• Evidence: Effective for CA-MRSA infections and may be preferred when doxycycline or TMP-SMX fails 1, 2

Second-Line Oral Agents

Linezolid

• Adult dosing: 600 mg orally twice daily 1
• Pediatric dosing: 10 mg/kg/dose orally every 8 hours, not to exceed 600 mg/dose 1
• FDA approval: Approved for SSTI with demonstrated efficacy (79% cure rate in MRSA SSTI) 3
• Major limitation: Not superior to less expensive alternatives and significantly more costly 1
• When to consider: Reserve for patients who fail first-line therapy or have contraindications to other agents 1

Tedizolid

• Recommendation: Suggested as an alternative oral agent for MRSA SSTI 1
• Advantage: Newer oxazolidinone with potentially improved safety profile compared to linezolid 1

Treatment Duration and Clinical Approach

Standard Duration

• 7-14 days is recommended for most MRSA SSTI, based on clinical response 1
• Treatment should continue for at least 48 hours after the patient becomes afebrile and asymptomatic in severe cases 4

When Oral Therapy is Appropriate

• Simple abscesses after incision and drainage 1
• Purulent cellulitis without systemic signs 1
• Patients who can tolerate oral medications and have reliable follow-up 1

When to Avoid Oral Therapy and Use Parenteral Treatment

Oral antibiotics should NOT be used in the following situations: 1, 4

• Severe or extensive disease involving multiple sites of infection 1
• Rapid progression with associated cellulitis 1
• Signs and symptoms of systemic illness (fever, hypotension, altered mental status) 1, 4
• Associated comorbidities or immunosuppression (diabetes, HIV/AIDS, malignancy) 1
• Extremes of age 1
• Abscess in areas difficult to drain completely (face, hand, genitalia) 1
• Associated septic phlebitis 1
• Lack of response to incision and drainage alone 1

Critical Clinical Pearls

Incision and Drainage

• For simple abscesses or boils, incision and drainage alone may be adequate without antibiotics 1
• In healthy patients with small purulent lesions, drainage alone may be sufficient 5

Streptococcal Coverage Considerations

• For nonpurulent cellulitis, empirical coverage for β-hemolytic streptococci is recommended with a β-lactam (e.g., cephalexin) 1
• If MRSA coverage is also needed for nonpurulent cellulitis, use clindamycin alone OR combine TMP-SMX or doxycycline with a β-lactam (e.g., amoxicillin, cephalexin) 1

Rifampin Warning

• Never use rifampin as monotherapy due to rapid development of resistance 1
• Adjunctive rifampin with another active drug is not recommended for SSTI in the absence of supporting data 1

Resistance Monitoring

• Always obtain culture specimens for documentation and susceptibility testing 5
• Test for inducible clindamycin resistance (D-test) before using clindamycin for serious infections 1