What are the first-line antibiotic treatments for cellulitis?

First-Line Antibiotic Treatment for Cellulitis

For non-purulent cellulitis, first-line treatment should be antibiotics active against beta-hemolytic streptococci, such as penicillin, amoxicillin, dicloxacillin, or cephalexin for 5 days, with extension if no improvement is seen. 1

Pathogen Considerations

• Cellulitis is primarily caused by beta-hemolytic streptococci, with Staphylococcus aureus less frequently involved unless associated with penetrating trauma or an underlying abscess 1
• In the majority of non-purulent, uncomplicated cases of cellulitis, the causative organisms are β-hemolytic streptococci or methicillin-sensitive Staphylococcus aureus 2
• Only about 15% of cellulitis cases have identifiable organisms, as most are non-culturable 3

Treatment Algorithm Based on Severity

Mild Non-Purulent Cellulitis

• First-line therapy should target streptococci with options including: 4, 1
  • Penicillin
  • Amoxicillin
  • Dicloxacillin
  • Cephalexin (e.g., cephalexin 500 mg orally four times daily)
• For penicillin-allergic patients, alternatives include: 4, 1
  • Clindamycin (e.g., 300-450 mg orally three times daily)
  • Erythromycin
  • Levofloxacin (for patients with severe penicillin allergy) 1

Purulent Cellulitis

• For cellulitis associated with purulent drainage or exudate without a drainable abscess, empirical therapy for CA-MRSA is recommended pending culture results 4
• Options include: 4
  • Clindamycin (A-I evidence)
  • Trimethoprim-sulfamethoxazole (A-II evidence)
  • Tetracyclines (doxycycline or minocycline) (A-II evidence)
  • Linezolid (A-II evidence)

Severe or Complicated Cellulitis

• For hospitalized patients with complicated skin and skin structure infections, empirical therapy for MRSA should be considered pending culture data 4, 1
• Options include: 4
  • IV vancomycin (A-I evidence)
  • Linezolid 600 mg PO/IV twice daily (A-I evidence)
  • Daptomycin 4 mg/kg/dose IV once daily (A-I evidence)
  • Telavancin 10 mg/kg/dose IV once daily (A-I evidence)
  • Clindamycin 600 mg IV/PO three times a day (A-III evidence)

Treatment Duration

• The American College of Physicians recommends a 5-day course of antibiotics for non-purulent cellulitis 1, 3
• Treatment should be extended if no improvement is seen after 5 days 1
• For severe or complicated cellulitis, 7-14 days of therapy is recommended, individualized based on clinical response 4

Special Considerations

MRSA Coverage

• Despite rising rates of community-acquired MRSA, coverage for non-purulent cellulitis is generally not recommended unless specific risk factors are present 2
• Consider MRSA coverage for cellulitis with: 4, 3
  • Penetrating trauma
  • Evidence of MRSA elsewhere
  • Nasal colonization with MRSA
  • Injection drug use
  • Purulent drainage
  • Systemic inflammatory response syndrome
  • High-risk populations (athletes, children, men who have sex with men, prisoners, military recruits, residents of long-term care facilities)

Combination Therapy

• If coverage for both beta-hemolytic streptococci and CA-MRSA is desired, options include: 4
  • Clindamycin alone (A-II evidence)
  • Trimethoprim-sulfamethoxazole or a tetracycline in combination with a beta-lactam, such as amoxicillin (A-II evidence)
  • Linezolid alone (A-II evidence)

Adjunctive Measures

• Elevate the affected area to promote gravity drainage of edema and inflammatory substances 1
• Treat predisposing conditions such as edema, tinea pedis, or other toe web abnormalities 1
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adult patients to hasten resolution 1

Common Pitfalls to Avoid

• Failure to examine interdigital toe spaces for fissuring, scaling, or maceration that may harbor pathogens 1
• Not elevating the affected area, which delays improvement 1
• Inadequate treatment duration when clinical improvement is not evident after 5 days 1
• Misdiagnosis of cellulitis mimickers such as venous stasis dermatitis, contact dermatitis, eczema, lymphedema, and erythema migrans 2
• Unnecessary MRSA coverage for typical non-purulent cellulitis in the absence of specific risk factors 2