Oral Antibiotics for Outpatient Treatment of Uncomplicated Skin and Soft Tissue Infections
For uncomplicated skin and soft tissue infections in the outpatient setting, first-line oral antibiotics are trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 double-strength tablets twice daily, doxycycline 100 mg twice daily, or clindamycin 300-450 mg three times daily, with treatment duration of 5-10 days. 1
First-Line Oral Antibiotic Options
For MRSA Coverage (Purulent Infections)
TMP-SMX (160-320/800-1600 mg orally every 12 hours) is a preferred first-line agent due to bactericidal activity, lower cost, and proven efficacy in randomized trials 2, 1
Doxycycline (100 mg orally every 12 hours) is equally preferred with excellent in vitro activity against community-acquired MRSA and demonstrated clinical effectiveness 2, 1
Clindamycin (300-450 mg orally three times daily) has the advantage of covering both MRSA and β-hemolytic streptococci, making it particularly useful for nonpurulent cellulitis 2, 1
Linezolid (600 mg orally every 12 hours) is an alternative option but is more expensive and typically reserved when other agents cannot be used 2, 3
For Non-Purulent Cellulitis (Streptococcal Coverage)
β-lactam antibiotics such as cephalexin (500 mg three times daily) or amoxicillin (500 mg three times daily) are appropriate when streptococcal infection is suspected without MRSA 2, 4
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
Treatment Duration and Clinical Approach
Standard treatment duration is 5-10 days for outpatient SSTI, based on clinical response 2, 1
For simple abscesses or boils, incision and drainage alone may be adequate without antibiotics, as cure rates of 90.5% have been demonstrated with drainage alone even in MRSA infections 1, 5
Oral therapy is appropriate for simple abscesses after incision and drainage, purulent cellulitis without systemic signs, and patients who can tolerate oral medications with reliable follow-up 1
Special Situations
Animal Bites
Amoxicillin-clavulanate (875/125 mg orally twice daily) is the preferred oral agent for animal bites, providing coverage against Pasteurella multocida and anaerobes 2
Doxycycline (100 mg twice daily) is an alternative with excellent activity against P. multocida, though some streptococci may be resistant 2
Human Bites
- Amoxicillin-clavulanate (875/125 mg orally twice daily) is also the preferred agent for human bites, covering Eikenella species and oral anaerobes 2
Erysipeloid
- Penicillin (500 mg four times daily) or amoxicillin (500 mg three times daily) for 7-10 days is recommended 2
Critical Clinical Pearls and Pitfalls
Never use rifampin as monotherapy due to rapid development of resistance; adjunctive rifampin with another active drug is not recommended for SSTI in the absence of supporting data 1
Test for inducible clindamycin resistance (D-test) before using clindamycin for serious infections, as cross-resistance with erythromycin-resistant strains can occur 1
Obtain culture specimens for documentation and susceptibility testing whenever possible, particularly for purulent infections 1
Empirical β-lactam antibiotics may no longer be appropriate as monotherapy in areas with high community-acquired MRSA prevalence, as 87.8% of S. aureus isolates in recent studies were MRSA 5
Avoid broad-spectrum agents with gram-negative activity (such as fluoroquinolones) for uncomplicated SSTI unless specifically indicated, as approximately 46% of cases involve avoidable antibiotic exposure 6
Treatment courses of 10 or more days are often unnecessary; short courses of 5-7 days are typically sufficient and can reduce antibiotic exposure by 19-55% 6