What is the best oral antibiotic for an adult patient with facial cellulitis, considering potential allergies to penicillin or amoxicillin?

Best Oral Antibiotic for Facial Cellulitis

For typical nonpurulent facial cellulitis in adults, cephalexin 500 mg orally every 6 hours for 5 days is the preferred first-line treatment, providing excellent coverage against the primary pathogens (beta-hemolytic streptococci and methicillin-sensitive S. aureus) with a 96% success rate. 1

First-Line Treatment Algorithm

Standard Therapy (No Penicillin/Cephalosporin Allergy)

• Cephalexin 500 mg orally every 6 hours is the preferred oral beta-lactam for facial cellulitis, targeting Streptococcus pyogenes and methicillin-sensitive Staphylococcus aureus 1, 2
• Alternative beta-lactam options include dicloxacillin 250-500 mg every 6 hours or amoxicillin-clavulanate 875/125 mg twice daily 3, 1
• Treat for exactly 5 days if clinical improvement occurs—extending beyond this timeframe is only necessary if symptoms have not improved 1, 2

The evidence strongly supports beta-lactam monotherapy as standard of care, with MRSA being an uncommon cause of typical facial cellulitis even in high-prevalence settings 1. The 2026 IDSA guidelines emphasize that adding MRSA coverage reflexively represents overtreatment in most cases 1.

For Penicillin/Cephalosporin Allergy

• Clindamycin 300-450 mg orally every 6 hours for 5 days is the optimal choice for allergic patients, providing single-agent coverage for both streptococci and MRSA without requiring combination therapy 1, 4
• Clindamycin should only be used if local MRSA clindamycin resistance rates are <10% 1
• 99.5% of S. pyogenes strains remain susceptible to clindamycin, making it highly effective for streptococcal coverage 3, 2

When to Add MRSA Coverage

Do NOT routinely add MRSA coverage for typical facial cellulitis. 1, 2 Add MRSA-active antibiotics ONLY when specific risk factors are present:

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate visible on examination 1, 2
• Evidence of MRSA infection elsewhere or known nasal MRSA colonization 1, 2
• Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, hypotension, or altered mental status 1

MRSA Coverage Options (When Indicated)

• Clindamycin 300-450 mg orally every 6 hours provides single-agent coverage for both streptococci and MRSA 1, 4
• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS a beta-lactam (cephalexin or amoxicillin) for dual coverage 1, 2
• Doxycycline 100 mg twice daily PLUS a beta-lactam—never use doxycycline as monotherapy due to unreliable streptococcal coverage 1

In a high MRSA-prevalence area, antibiotics without MRSA activity had 4.22 times higher odds of treatment failure (95% CI 2.25-7.92) 5. However, this applies primarily to purulent cellulitis, not typical nonpurulent facial cellulitis 1.

Special Considerations for Facial Cellulitis

Odontogenic Origin

• If facial cellulitis originates from dental infection, amoxicillin-clavulanate 875/125 mg twice daily provides optimal polymicrobial coverage including anaerobes 1, 6
• Dental abscesses are polymicrobial aerobic/anaerobic infections requiring coverage beyond typical cellulitis pathogens 6

Hospitalization Criteria

Admit patients with facial cellulitis who have:

• SIRS criteria (fever, tachycardia, hypotension, altered mental status) 1, 2
• Extensive facial involvement with toxic appearance 7
• Concern for deeper or necrotizing infection 1
• Severe immunocompromise or neutropenia 1

For hospitalized patients, cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam, or vancomycin 15-20 mg/kg IV every 8-12 hours if MRSA coverage is needed 1.

Essential Adjunctive Measures

• Elevate the affected area to promote gravity drainage of edema and inflammatory substances—this hastens clinical improvement 1, 2
• Treat predisposing conditions including tinea pedis, trauma, or venous eczema 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in nondiabetic adults, though evidence is limited 1

Critical Pitfalls to Avoid

• Do not extend treatment beyond 5 days automatically—only extend if clinical improvement has not occurred within this timeframe 1, 2
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1
• Do not add MRSA coverage reflexively for typical nonpurulent facial cellulitis without specific risk factors—this increases antibiotic resistance without improving outcomes 1, 2
• Reassess within 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some oral regimens 3

Treatment Failure Management

If facial cellulitis progresses despite appropriate beta-lactam therapy after 48-72 hours:

• Add empiric MRSA coverage immediately with trimethoprim-sulfamethoxazole, doxycycline, or clindamycin 1
• Evaluate for warning signs of necrotizing fasciitis: severe pain out of proportion to examination, skin anesthesia, rapid progression, "wooden-hard" subcutaneous tissues, or systemic toxicity 1
• Consider alternative diagnoses including abscess requiring drainage, deep vein thrombosis, or misdiagnosis 1
• Obtain blood cultures and consider wound culture if any drainage present 1