What are the first-line antibiotic choices for a typical adult patient with a soft tissue infection, such as cellulitis or abscess, without any specific contraindications or allergies?

First-Line Antibiotic Choices for Soft Tissue Infections

For typical uncomplicated cellulitis in adults, beta-lactam monotherapy with oral cephalexin, dicloxacillin, or amoxicillin is the standard of care, achieving 96% success rates without requiring MRSA coverage. 1

Standard Treatment for Nonpurulent Cellulitis

Recommended oral agents include:

• Cephalexin 500 mg every 6 hours 1, 2
• Dicloxacillin 250-500 mg every 6 hours 1, 2
• Amoxicillin (dose equivalent to above agents) 1
• Penicillin V 250-500 mg four times daily 1

Treatment duration is 5 days if clinical improvement occurs, extending only if symptoms have not improved within this timeframe. 1, 2 This represents a significant departure from traditional 7-14 day courses, with high-quality randomized controlled trial evidence demonstrating that 5-day courses are equally effective as 10-day courses for uncomplicated cellulitis. 1

When MRSA Coverage is NOT Needed

MRSA is an uncommon cause of typical cellulitis even in high-prevalence hospital settings, and routine MRSA coverage represents overtreatment. 1, 2 The Infectious Diseases Society of America explicitly states that beta-lactam treatment succeeds in 96% of patients, confirming MRSA coverage is usually unnecessary. 1

When to Add MRSA Coverage

Add MRSA-active antibiotics ONLY when specific risk factors are present: 1, 2

• Penetrating trauma or injection drug use
• Purulent drainage or exudate visible
• Evidence of MRSA infection elsewhere or known nasal colonization
• Systemic inflammatory response syndrome (SIRS) with fever, tachycardia, or hypotension
• Failure to respond to beta-lactam therapy after 48-72 hours

For MRSA coverage, use: 1, 2

• Clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA, avoiding need for combination therapy) 1, 2
• Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 DS tablets twice daily PLUS a beta-lactam (cephalexin or amoxicillin) 1, 2
• Doxycycline 100 mg twice daily PLUS a beta-lactam 1, 2

Critical caveat: Never use TMP-SMX or doxycycline as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 1, 2

Purulent Infections (Abscesses)

For abscesses, incision and drainage is the primary treatment, with antibiotics playing only a subsidiary role. 1, 2 If antibiotics are indicated after drainage, use MRSA-active agents listed above. 1

Intravenous Options for Hospitalized Patients

For uncomplicated cellulitis requiring hospitalization without MRSA risk factors: 1

• Cefazolin 1-2 g IV every 8 hours (preferred) 1, 2
• Oxacillin or nafcillin 2 g IV every 6 hours (alternatives) 1, 2

For complicated cellulitis with MRSA coverage needed: 1, 3

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1, 3
• Linezolid 600 mg IV twice daily (equally effective alternative, A-I evidence) 1, 3
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 1, 3
• Clindamycin 600 mg IV every 8 hours (if local MRSA resistance <10%, A-III evidence) 1

Severe Infections Requiring Broad-Spectrum Coverage

For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis, mandatory broad-spectrum combination therapy includes: 1, 2

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1
• OR vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1
• OR vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours 1

For documented group A streptococcal necrotizing fasciitis specifically, use penicillin plus clindamycin. 4, 1

Special Situations

Animal or human bites: 4, 1

• Amoxicillin-clavulanate 875/125 mg twice daily (provides single-agent polymicrobial coverage)

Diabetic foot infections (mild to moderate): 4, 1

• Amoxicillin-clavulanate, ampicillin-sulbactam, or second/third-generation cephalosporins (cefuroxime, ceftriaxone)

Essential Adjunctive Measures

Elevation of the affected extremity hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1, 2 This simple intervention is critical and often neglected. 1

Treat predisposing conditions: 1, 2

• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration
• Address venous insufficiency, lymphedema, and chronic edema
• Manage obesity and eczema

Common Pitfalls to Avoid

Do not routinely add MRSA coverage for typical nonpurulent cellulitis without specific risk factors — this increases antibiotic resistance without improving outcomes. 1, 2

Do not extend treatment beyond 5 days automatically — only extend if clinical improvement has not occurred within this timeframe. 1, 2

Do not use combination therapy when monotherapy is appropriate — this increases adverse effects without benefit. 1

Do not delay surgical consultation if necrotizing infection is suspected — these infections progress rapidly and require emergent debridement. 1