What is the preferred antibiotic, Augmentin (amoxicillin/clavulanate) or Bactrim (trimethoprim/sulfamethoxazole), for treating cellulitis?

Antibiotic Choice for Cellulitis: Augmentin vs Bactrim

For typical cellulitis without purulent drainage or abscess, neither Augmentin nor Bactrim is the preferred first-line agent—a beta-lactam alone (cephalexin, dicloxacillin, or penicillin) is recommended because streptococci are the primary pathogen and MRSA is uncommon. 1, 2

First-Line Treatment Algorithm

Use a beta-lactam alone as first-line therapy:

• Cephalexin 500 mg every 6 hours is the preferred oral agent 2
• Dicloxacillin is equally effective 2
• Amoxicillin or penicillin are acceptable alternatives 1
• Treat for 5 days if clinical improvement occurs; extend only if no improvement 1, 2

Between your two options, Augmentin is superior to Bactrim for typical cellulitis because it provides direct coverage against streptococci (the primary pathogen), whereas TMP-SMX has uncertain activity against beta-hemolytic streptococci and should not be used as monotherapy. 1

When to Choose Augmentin Over Simple Beta-Lactams

Consider Augmentin specifically when:

• Recent amoxicillin use (suggests beta-lactamase producing organisms) 2
• Traumatic wounds or bite injuries 2
• Failure to respond to simple beta-lactams 2
• Mixed infection suspected (provides broader staphylococcal coverage including beta-lactamase producers) 2, 3

Clinical evidence supports Augmentin: A retrospective study of 59 hospitalized patients showed amoxicillin-clavulanate was associated with shorter hospital stays (7.0 ± 2.9 days) and less frequent antibiotic changes compared to cephalosporins or clindamycin. 4

When to Add MRSA Coverage (Making Bactrim Relevant)

Add MRSA-active therapy only when specific risk factors are present:

• Purulent drainage or exudate visible 1, 2
• Penetrating trauma, especially injection drug use 1
• Known MRSA colonization or infection elsewhere 1, 2
• Failure of beta-lactam therapy after 48 hours 1
• Systemic inflammatory response syndrome (fever, hypotension, altered mental status) 2

If MRSA coverage is needed, use combination therapy:

• Clindamycin alone (covers both streptococci and MRSA) 1, 2
• TMP-SMX PLUS a beta-lactam (cephalexin, amoxicillin, or penicillin) to ensure streptococcal coverage 1, 2
• Doxycycline or minocycline PLUS a beta-lactam 1

Critical Evidence Against Bactrim Monotherapy

A randomized controlled trial directly tested your question: 146 patients with non-purulent cellulitis received either cephalexin alone or cephalexin plus TMP-SMX. The addition of TMP-SMX provided no benefit—cure rates were 85% vs 82% (risk difference 2.7%, p=0.66). 5 This demonstrates that routine MRSA coverage with TMP-SMX is unnecessary and adds no value for typical cellulitis.

MRSA is an unusual cause of typical cellulitis: A prospective study showed beta-lactams (cefazolin/oxacillin) were successful in 96% of cellulitis cases, confirming MRSA is rarely the culprit. 1

Dosing Considerations If Using TMP-SMX

If you do prescribe TMP-SMX for MRSA coverage, use adequate weight-based dosing:

• Minimum 5 mg TMP/kg/day (typically TMP-SMX DS 1-2 tablets twice daily for adults >60 kg) 6
• A retrospective study of 208 hospitalized patients showed inadequate dosing (<5 mg TMP/kg/day) was independently associated with clinical failure (30% vs 17%, OR 2.01, p=0.032) 6

Common Pitfalls to Avoid

Do not routinely cover MRSA in typical cellulitis—this is the most common error. MRSA coverage is unnecessary in 96% of cases without specific risk factors. 1, 2

Do not use TMP-SMX as monotherapy for cellulitis—its activity against streptococci is uncertain, and streptococci are the primary pathogen. Always combine with a beta-lactam if MRSA coverage is needed. 1

Do not automatically treat for 10-14 days—5 days is as effective as 10 days for uncomplicated cellulitis if clinical improvement occurs. 1, 2

Adjunctive Measures

Always address predisposing factors:

• Elevate the affected extremity to promote drainage 1, 2
• Examine and treat tinea pedis, toe web maceration, or fissuring 2
• Manage venous insufficiency, lymphedema, or eczema 1, 2

Summary Decision Tree

1. Typical cellulitis (no purulent drainage, no risk factors): Use cephalexin or dicloxacillin alone for 5 days 1, 2
2. If choosing between Augmentin vs Bactrim for typical cellulitis: Choose Augmentin—it covers streptococci directly 2, 4
3. If MRSA risk factors present: Use clindamycin alone OR TMP-SMX plus cephalexin 1, 2
4. If failed beta-lactam therapy: Add MRSA coverage with clindamycin or TMP-SMX plus beta-lactam 1