What oral antibiotic is recommended for an uncomplicated skin or soft tissue infection?

Oral Antibiotic for Uncomplicated Skin and Soft Tissue Infections

For uncomplicated skin and soft tissue infections, cephalexin 500 mg orally every 6 hours (or 500 mg every 12 hours for mild cases) is the recommended first-line oral antibiotic, targeting the most common pathogens—streptococci and methicillin-susceptible Staphylococcus aureus. 1

Primary Recommendation: Beta-Lactam Antibiotics

For typical uncomplicated SSTIs without purulent drainage or systemic signs of infection, beta-lactam antibiotics remain the cornerstone of therapy because they provide excellent coverage against streptococci, which are the predominant pathogens in non-purulent cellulitis. 1

First-Line Options:

• Cephalexin 500 mg orally every 6 hours (or 500 mg every 12 hours for streptococcal pharyngitis and uncomplicated skin infections) 1, 2
• Dicloxacillin 500 mg orally four times daily 1
• Amoxicillin 500 mg three times daily 1
• Penicillin 500 mg orally four times daily 1

Duration: 5-7 days is as effective as 10 days if clinical improvement occurs by day 5. 1

When to Consider MRSA Coverage

MRSA is an uncommon cause of typical non-purulent cellulitis—studies show 96% success rates with beta-lactams alone even in high-MRSA prevalence areas. 1 However, add MRSA coverage when:

• Purulent drainage is present 1
• Penetrating trauma, especially injection drug use 1
• Evidence of MRSA infection elsewhere 1
• Systemic signs of infection (SIRS criteria) 1
• Treatment failure with beta-lactam therapy 1

MRSA-Active Oral Options:

• Clindamycin 300-450 mg orally four times daily (covers both streptococci and MRSA) 1, 3
• Trimethoprim-sulfamethoxazole (TMP-SMX) 160-800 mg twice daily PLUS a beta-lactam (cephalexin or amoxicillin) for dual streptococcal/MRSA coverage 1
• Doxycycline 100 mg twice daily PLUS a beta-lactam for dual coverage 1

Critical caveat: TMP-SMX and doxycycline have unreliable activity against beta-hemolytic streptococci when used alone, so never use them as monotherapy for non-purulent cellulitis. 1 A recent double-blind trial confirmed that TMP-SMX plus cephalexin was no more effective than cephalexin alone for pure cellulitis without abscess. 1

Special Circumstances

Animal Bites:

Amoxicillin-clavulanate 500/875 mg twice daily is the preferred oral agent, providing coverage for Pasteurella multocida, streptococci, staphylococci, and anaerobes. 1

Human Bites:

Amoxicillin-clavulanate 500 mg every 8 hours covers Eikenella corrodens, streptococci, staphylococci, and anaerobes. 1

Penicillin Allergy:

• Clindamycin 300 mg three times daily (good for staphylococci, streptococci, and anaerobes) 1
• Fluoroquinolones (ciprofloxacin 500-750 mg twice daily, levofloxacin 750 mg daily, or moxifloxacin 400 mg daily) 1

Evidence Regarding Antibiotics vs. Drainage Alone

For simple abscesses, incision and drainage alone may be sufficient without antibiotics. A randomized placebo-controlled trial showed 90.5% cure rates with drainage alone versus 84.1% with drainage plus cephalexin in MRSA-predominant abscesses. 4 However, add antibiotics when:

• Erythema extending >5 cm from wound edge 1
• Systemic signs (temperature >38.5°C, heart rate >110 bpm) 1
• Multiple lesions 1
• Immunocompromised state 1

Pediatric Considerations

For children with uncomplicated SSTIs, cephalexin 25-50 mg/kg/day in divided doses is appropriate, with the option to divide doses every 12 hours for streptococcal pharyngitis and skin infections. 2 A pediatric randomized trial found no significant difference between cephalexin and clindamycin for CA-MRSA infections when appropriate drainage was performed, emphasizing that fastidious wound care and close follow-up are more important than initial antibiotic choice. 5

Common Pitfalls to Avoid

• Do not routinely cover for MRSA in non-purulent cellulitis—this leads to unnecessary broad-spectrum antibiotic use. 1
• Do not use TMP-SMX or doxycycline as monotherapy for cellulitis without purulent drainage due to poor streptococcal coverage. 1
• Do not prescribe antibiotics for simple abscesses if adequate drainage is achieved and no systemic signs are present. 4
• Avoid fluoroquinolones in children <18 years and tetracyclines in children <8 years. 1