What is the recommended antibiotic for facial cellulitis?

Recommended Antibiotic for Facial Cellulitis

For typical nonpurulent facial cellulitis, beta-lactam monotherapy with oral cephalexin, dicloxacillin, or amoxicillin for 5 days is the standard of care, achieving 96% success rates without requiring MRSA coverage. 1

First-Line Treatment Selection

Beta-lactam monotherapy is appropriate for most cases:

• Cephalexin 500 mg orally four times daily for 5 days if clinical improvement occurs 1
• Dicloxacillin 250-500 mg orally every 6 hours for 5 days 1
• Amoxicillin at standard dosing for 5 days 1
• Penicillin V 250-500 mg orally four times daily for 5 days 1

These agents provide excellent coverage against beta-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus, which are the primary pathogens in typical facial cellulitis. 1 MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings, making routine MRSA coverage unnecessary. 1

Treatment Duration

Treat for exactly 5 days if clinical improvement has occurred; extend only if symptoms have not improved within this timeframe. 1 Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 1

When to Add MRSA Coverage

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

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1
• 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

If MRSA coverage is needed, use:

• Clindamycin 300-450 mg orally every 6 hours as monotherapy (covers both streptococci and MRSA) 1
• Trimethoprim-sulfamethoxazole PLUS a beta-lactam (e.g., cephalexin) 1
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam (age >8 years only) 1, 2

Clindamycin monotherapy is particularly advantageous because it provides single-agent coverage for both streptococci and MRSA, avoiding the need for combination therapy. 1 However, clindamycin should only be used if local MRSA clindamycin resistance rates are <10%. 1

Special Considerations for Facial Cellulitis

Preseptal (Periorbital) Cellulitis

For preseptal cellulitis specifically:

• Amoxicillin-clavulanate is first-line for mild cases requiring broader coverage of mixed infections 2
• Daily follow-up is mandatory until definite improvement is noted 2
• Hospitalize immediately if proptosis, impaired visual acuity, or impaired/painful extraocular mobility is present, as these indicate orbital involvement requiring IV therapy 2

Odontogenic Facial Cellulitis

For facial cellulitis of dental origin:

• Amoxicillin-clavulanate 875/125 mg orally twice daily provides single-agent coverage for polymicrobial oral flora 1, 3
• Surgical drainage (extraction or root canal) is essential within 24 hours of presentation 3
• Both ampicillin/sulbactam and clindamycin combined with surgical drainage are very effective 3

Severe Facial Cellulitis Requiring Hospitalization

Hospitalize if any of the following are present:

• Systemic inflammatory response syndrome (SIRS), fever, hypotension, or altered mental status 1
• Rapid progression or concern for necrotizing fasciitis 1
• Severe immunocompromise or neutropenia 1

For hospitalized patients with severe facial cellulitis:

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours for suspected necrotizing infection or systemic toxicity 1
• Alternative IV monotherapy options include cefazolin 1-2 g IV every 8 hours for uncomplicated cases without MRSA risk factors 1

Common Pitfalls to Avoid

Do not routinely add MRSA coverage for typical nonpurulent facial cellulitis without specific risk factors, as this represents overtreatment and increases antibiotic resistance. 1 Adding MRSA coverage to beta-lactam therapy provides no additional benefit in typical cases. 1

Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 1 These agents must be combined with a beta-lactam when treating typical nonpurulent cellulitis. 1

Do not delay hospitalization if there is any concern for orbital involvement in preseptal cellulitis or if outpatient therapy fails within 24-48 hours. 2

Evidence Quality Note

The recommendation for beta-lactam monotherapy is supported by high-quality evidence showing 96% success rates. 1 A randomized controlled trial demonstrated that combination therapy with trimethoprim-sulfamethoxazole plus cephalexin is no more efficacious than cephalexin alone in pure cellulitis without abscess, ulcer, or purulent drainage. 4 However, in MRSA-prevalent settings, antibiotics with activity against MRSA (trimethoprim-sulfamethoxazole, clindamycin) showed significantly higher success rates than cephalexin alone when MRSA was subsequently culture-confirmed. 5