What is the recommended oral antibiotic treatment for an adult patient with uncomplicated cellulitis and no known allergies to penicillin (Penicillin)?

Oral Antibiotic Treatment for Uncomplicated Cellulitis

For an adult with uncomplicated cellulitis and no penicillin allergy, prescribe cephalexin 500 mg orally four times daily for exactly 5 days if clinical improvement occurs—extending treatment only if warmth, tenderness, and erythema have not improved within this timeframe. 1, 2

Why Beta-Lactam Monotherapy Is the Standard of Care

• Beta-lactam monotherapy succeeds in 96% of uncomplicated cellulitis cases, confirming that MRSA coverage is unnecessary in typical presentations. 1, 2

• MRSA is an uncommon cause of typical nonpurulent cellulitis, even in hospitals with high MRSA prevalence. 1, 2

• Cephalexin provides excellent coverage against beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus—the predominant pathogens in nonpurulent cellulitis. 1, 2

Alternative Oral Beta-Lactam Options

If cephalexin is unavailable or not tolerated, equally effective alternatives include:

• Dicloxacillin 250-500 mg orally every 6 hours for 5 days 1
• Amoxicillin at standard dosing for 5 days 1
• Amoxicillin-clavulanate 875/125 mg twice daily for 5 days (particularly appropriate for bite-associated cellulitis) 1
• Penicillin V 250-500 mg orally four times daily for 5 days 1

Treatment Duration: The 5-Day Rule

• Treat for exactly 5 days if clinical improvement occurs—defined as resolution of warmth and tenderness, improving erythema, and absence of fever. 1, 2

• Extension beyond 5 days is warranted only if no improvement in warmth, tenderness, or erythema is observed, at which point reassess for complications, resistant organisms, or alternative diagnoses. 1, 2

• High-quality randomized controlled trial evidence demonstrates that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis, with 98% clinical success rates at both 14 and 28 days. 3

• Common pitfall to avoid: Do not reflexively extend treatment to 7-10 days based on residual erythema alone, as some inflammation persists even after bacterial eradication. 1

When Beta-Lactam Monotherapy Is NOT Appropriate

Do not use cephalexin or other beta-lactam monotherapy when MRSA risk factors are present: 1, 2

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate 1, 2
• Evidence of MRSA infection elsewhere or known MRSA colonization 1
• Systemic inflammatory response syndrome (SIRS) 1
• Failure to respond to beta-lactam therapy within 48 hours 1

For these scenarios, switch to clindamycin 300-450 mg orally four times daily, which covers both streptococci and MRSA without requiring combination therapy—but only if local MRSA clindamycin resistance rates are <10%. 1, 2

Essential Adjunctive Measures That Accelerate Recovery

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances. 1, 2

• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration—treating these eradicates colonization and reduces recurrent infection risk. 1, 2

• Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, and eczema to prevent recurrence. 1, 2

When to Hospitalize Instead of Treating Outpatient

Admit patients with any of the following: 1, 2

• Systemic inflammatory response syndrome (SIRS), hypotension, or altered mental status 1, 2
• Severe immunocompromise or neutropenia 1, 2
• Signs of necrotizing infection (severe pain out of proportion to examination, skin anesthesia, rapid progression, "wooden-hard" subcutaneous tissues, gas in tissue) 1

For hospitalized patients requiring IV therapy without MRSA risk factors, use cefazolin 1-2 g IV every 8 hours. 1, 2

For severe cellulitis with systemic toxicity or suspected necrotizing fasciitis, use vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours. 1, 2

Critical Evidence Nuance

While one retrospective study from Hawaii (a high MRSA-prevalence area) suggested trimethoprim-sulfamethoxazole had higher success rates than cephalexin (91% vs 74%), 4 this contradicts the IDSA's A-I level evidence demonstrating 96% success with beta-lactam monotherapy for typical nonpurulent cellulitis. 1 The Hawaii study likely included patients with purulent features or MRSA risk factors, making it less applicable to truly uncomplicated cellulitis. For typical nonpurulent cellulitis without MRSA risk factors, beta-lactam monotherapy remains the evidence-based standard. 1, 2