What is the recommended treatment for a typical adult patient with a bacterial skin infection, such as cellulitis or impetigo?

Treatment of Bacterial Skin Infections

For typical uncomplicated cellulitis in adults, beta-lactam monotherapy with cephalexin 500 mg orally four times daily for 5 days is the standard of care, achieving 96% success rates without requiring MRSA coverage. 1

First-Line Antibiotic Selection for Cellulitis

Beta-lactam antibiotics remain the cornerstone of treatment for nonpurulent cellulitis, as beta-hemolytic streptococci (particularly Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus are the primary pathogens. 2, 1 The Infectious Diseases Society of America provides A-I level evidence supporting this approach. 2

Recommended oral agents include:

• Cephalexin 500 mg every 6 hours (preferred first-line option) 1, 3
• Dicloxacillin 250-500 mg every 6 hours 1, 4
• Amoxicillin (appropriate for streptococcal coverage) 1
• Penicillin V 250-500 mg four times daily 1

Cephalexin offers the advantage of twice-daily dosing in some protocols, which enhances compliance, though four-times-daily dosing provides more consistent coverage. 4 Research comparing cephalexin to dicloxacillin demonstrated equal efficacy, with both achieving >95% clinical response rates in staphylococcal skin infections. 4, 3

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1 High-quality randomized controlled trials demonstrate that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis. 1 The traditional 7-14 day courses represent overtreatment in most cases and increase antibiotic resistance without improving outcomes. 1

When to Add MRSA Coverage

MRSA is an uncommon cause of typical cellulitis, even in high-prevalence settings, and routine coverage is unnecessary. 1 Add MRSA-active antibiotics ONLY when specific risk factors are present:

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 2, 1
• Evidence of MRSA infection elsewhere or known nasal colonization 1
• Systemic inflammatory response syndrome (SIRS) with fever >38°C, tachycardia >90 bpm, or hypotension 1
• Failure to respond to beta-lactam therapy after 48-72 hours 1

MRSA-active oral regimens when indicated:

• Clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA; use only if local resistance <10%) 2, 1
• Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 double-strength tablets twice daily PLUS a beta-lactam (amoxicillin or cephalexin) 2, 1
• Doxycycline 100 mg twice daily PLUS a beta-lactam 2, 1

Critical pitfall: Never use TMP-SMX or doxycycline as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 2, 1 These agents must be combined with a beta-lactam to ensure adequate streptococcal coverage. 1

Treatment of Impetigo

For minor skin infections like impetigo, mupirocin 2% topical ointment is effective and preferred. 2 This approach avoids systemic antibiotic exposure for localized superficial infections. 2

For more extensive impetigo requiring systemic therapy:

• Cephalexin 250 mg four times daily in adults 1
• Cephalexin 25 mg/kg/day in four divided doses for children 1

Hospitalization Criteria and IV Therapy

Admit patients with any of the following:

• SIRS criteria (fever, tachycardia, hypotension, altered mental status) 1
• Severe immunocompromise or neutropenia 1
• Concern for deeper or necrotizing infection 1
• Failure of outpatient treatment after 24-48 hours 1

For hospitalized patients with complicated cellulitis:

IV vancomycin 15-20 mg/kg every 8-12 hours is first-line therapy (A-I evidence). 2, 1 Alternative equally effective options include:

• Linezolid 600 mg IV twice daily (A-I evidence) 2, 5
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 2
• Clindamycin 600 mg IV three times daily (A-III evidence; only if local resistance <10%) 2

For uncomplicated cellulitis requiring hospitalization without MRSA risk factors:

• Cefazolin 1-2 g IV every 8 hours (preferred IV beta-lactam) 1

For severe cellulitis with systemic toxicity or suspected necrotizing fasciitis:

Mandatory broad-spectrum combination therapy with vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours. 1 This regimen provides coverage for polymicrobial infections including anaerobes and gram-negative organisms. 1 Treatment duration for severe infections is 7-14 days, individualized based on clinical response. 2

Essential Adjunctive Measures

Elevation of the affected extremity is critical and often neglected—it hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1 Elevate the limb above heart level for at least 30 minutes three times daily. 1

Additional measures that reduce recurrence:

• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration and treat aggressively 1
• Address venous insufficiency and lymphedema with compression stockings once acute infection resolves 1
• Treat underlying conditions including eczema, obesity, and chronic edema 1

Penicillin Allergy Considerations

For patients with penicillin allergy (except immediate hypersensitivity):

• Cephalexin remains an option, as cross-reactivity between penicillins and cephalosporins is only 2-4% 1
• Clindamycin 300-450 mg every 6 hours provides single-agent coverage for both streptococci and MRSA 1

For true penicillin AND cephalosporin allergy:

• Clindamycin monotherapy (if local resistance <10%) 1
• Linezolid 600 mg twice daily (expensive; reserve for complicated cases) 1

Common Pitfalls to Avoid

• Do not routinely add MRSA coverage for typical nonpurulent cellulitis without specific risk factors—this represents overtreatment and increases resistance 1
• Do not extend treatment beyond 5 days automatically—only extend if clinical improvement has not occurred 1
• Do not use doxycycline or TMP-SMX as monotherapy for cellulitis, as streptococcal coverage is inadequate 2, 1
• Do not delay surgical consultation if any signs of necrotizing infection are present (severe pain out of proportion to exam, skin anesthesia, rapid progression, "wooden-hard" tissues) 1
• Reassess within 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some regimens 1

Special Populations

Pediatric considerations:

• Mupirocin 2% topical ointment for minor infections like impetigo 2
• Never use tetracyclines in children <8 years due to tooth discoloration 2
• For hospitalized children: vancomycin 15 mg/kg IV every 6 hours (A-II evidence) 2
• Alternative: clindamycin 10-13 mg/kg/dose IV every 6-8 hours if stable and local resistance <10% 2

Diabetic foot infections:

Diabetic patients require broader coverage and longer duration due to polymicrobial infections. 1 For moderate infections, use amoxicillin-clavulanate, levofloxacin, or ceftriaxone. 1 For severe infections, use piperacillin-tazobactam, imipenem-cilastatin, or vancomycin plus ceftazidime. 1