What is the first-line treatment for skin infection or cellulitis?

First-Line Treatment for Skin Infection or Cellulitis

For uncomplicated cellulitis or skin infections, cephalexin (500 mg orally 3-4 times daily for 5-6 days) is the first-line treatment of choice. 1, 2

Antibiotic Selection Algorithm

First-Line Options (Uncomplicated Cases):

• Cephalexin: 500 mg orally 3-4 times daily for 5-6 days 1
  • Provides excellent coverage for Streptococcus and methicillin-sensitive Staphylococcus aureus (MSSA)
  • FDA-approved specifically for skin and skin structure infections 2

Alternative First-Line Options:

• Clindamycin: 300-450 mg orally three times daily for 5-6 days 1

  • Particularly useful for patients with severe penicillin allergy
  • Provides coverage for MRSA, streptococci, and anaerobes
  • Caution: Risk of Clostridioides difficile infection

• Amoxicillin-clavulanate: 875/125 mg twice daily orally for 5-6 days 1

  • Good option when anaerobic coverage is needed

• Doxycycline: 100 mg twice daily for 5-6 days 1

  • Alternative for penicillin-allergic patients
  • Contraindications: Children under 8 years (tooth discoloration), pregnant women in third trimester, infants younger than 2 months

Special Considerations

MRSA Coverage:

• Consider MRSA coverage if:
  • Previous MRSA infection or colonization
  • Failed initial antibiotic treatment
  • Purulent cellulitis
  • High local MRSA prevalence
  • Options include: trimethoprim-sulfamethoxazole, clindamycin, doxycycline 1, 3

Complicated Cases:

For complex patients with frequent hospitalizations or healthcare-associated infections:

• Piperacillin-tazobactam or carbapenem (e.g., meropenem) plus oxacillin 1
• Vancomycin, daptomycin, or linezolid for suspected MRSA 1
  • Monitor plasma levels with vancomycin, especially in patients with cirrhosis

Abscess Management:

• Incision and drainage is the primary treatment for abscesses 1
• Antibiotics are adjunctive therapy
• Cure rates of ~90% can be achieved with incision and drainage alone for uncomplicated abscesses

Treatment Duration and Monitoring

• Standard duration: 5-6 days for uncomplicated cases 1
• Most patients should show improvement within 48-72 hours of starting appropriate therapy
• If no improvement after 72 hours:
  1. Reevaluate diagnosis
  2. Consider changing antibiotic therapy
  3. Evaluate for abscess formation requiring drainage

Common Pitfalls to Avoid

1. Overtreatment with MRSA coverage when not indicated in areas with low MRSA prevalence 1
2. Unnecessarily prolonged treatment courses beyond 5-6 days for uncomplicated cases 1
3. Failure to distinguish cellulitis from pseudocellulitis (e.g., venous stasis dermatitis, contact dermatitis) 4
4. Not elevating affected limb when appropriate 1
5. Not addressing underlying predisposing factors 1
6. Inadequate dosing adjustments for renal impairment, especially with nephrotoxic antibiotics 1

Evidence Quality Assessment

The treatment recommendations are primarily based on the most recent and comprehensive guidelines from the Infectious Diseases Society of America, as summarized in Praxis Medical Insights 1. These guidelines represent the strongest evidence available and are consistent with the FDA-approved indications for cephalexin 2.

Research studies have confirmed that for uncomplicated cellulitis, cephalexin is effective as monotherapy 4, 5. A randomized controlled trial showed that adding trimethoprim-sulfamethoxazole to cephalexin did not improve outcomes for uncomplicated cellulitis 5, supporting the recommendation for cephalexin as first-line therapy.