What antibiotics are recommended for treating cellulitis of the legs?

Antibiotic Treatment for Cellulitis of the Legs

For non-purulent cellulitis of the legs, first-line treatment is a first-generation cephalosporin like cephalexin (500 mg 3-4 times daily for 5-6 days), which targets the most common causative organisms: beta-hemolytic Streptococcus and methicillin-sensitive Staphylococcus aureus. 1, 2

First-Line Treatment Options

• Cephalexin: 500 mg orally 3-4 times daily for 5-6 days
  • Targets Streptococcus and methicillin-sensitive S. aureus (MSSA)
  • Preferred for uncomplicated cellulitis without purulence

When to Consider MRSA Coverage

Consider MRSA coverage if any of these risk factors are present:

• Previous MRSA infection
• Purulent drainage
• Failure to respond to beta-lactam therapy within 48-72 hours
• High-risk populations: athletes, children, men who have sex with men, prisoners, military recruits, residents of long-term care facilities, intravenous drug users 1, 2

MRSA coverage options:

• Clindamycin: 300-450 mg orally three times daily for 5-6 days 1
• Trimethoprim-sulfamethoxazole (TMP-SMX): 1-2 DS tablets twice daily for 5-6 days 1, 3
  • Note: In areas with high MRSA prevalence, TMP-SMX has shown higher success rates (91%) compared to cephalexin (74%) 3

Special Situations

Beta-lactam Allergy

• Clindamycin: 300-450 mg orally three times daily for 5-6 days
  • Provides good coverage against anaerobes and Staphylococcus
  • Caution: risk of C. difficile colitis 1

Severe Infections

For patients with systemic signs of illness (temperature >38°C, tachycardia, tachypnea, or abnormal WBC count):

• Consider broader-spectrum antibiotics
• Evaluate for hospitalization if SIRS, altered mental status, or hemodynamic instability present 1

Polymicrobial Infections

• Amoxicillin-clavulanate: 875/125 mg twice daily for 5-6 days
  • Broader coverage for mixed flora 1

Treatment Duration

• 5-6 days is sufficient for uncomplicated cellulitis 1, 4
• Extend treatment if symptoms have not improved after initial course
• A randomized trial showed 5 days of therapy was as effective as 10 days (98% success in both groups) 4

Treatment Monitoring and Follow-up

• Reevaluate within 48-72 hours to assess treatment response
• If no improvement after 48-72 hours, consider:
  • Adding MRSA coverage if not already included
  • Possible alternative diagnosis
  • Need for incision and drainage if abscess has developed 1

Supportive Care

• Elevation of the affected leg to reduce edema
• Keep the area clean and dry
• Apply warm compresses if needed
• Daily cleansing with chlorhexidine or povidone-iodine solution may be considered 1

Key Pitfalls to Avoid

• Failing to consider MRSA in patients with risk factors or non-responsive infections
• Treating for too short a duration in severe cases
• Not addressing predisposing factors that can lead to recurrence
• Using antibiotics without appropriate anaerobic coverage when needed
• Stopping antibiotics too early when symptoms improve 1, 2

Remember that the diagnosis of cellulitis is primarily clinical, and cultures are often negative. Treatment should be directed at the most likely pathogens while considering local resistance patterns.