What is the recommended treatment for uncomplicated cellulitis?

Treatment of Uncomplicated Cellulitis

For uncomplicated cellulitis, a 5- to 6-day course of antibiotics active against streptococci is the recommended treatment, particularly for patients able to self-monitor and who have close follow-up with primary care. 1

First-Line Antibiotic Options

• Cephalexin 500 mg orally four times daily for 5-6 days is a preferred first-line treatment as streptococci are the most common causative pathogens in cellulitis 2, 3
• Penicillin or amoxicillin can be used when primarily targeting streptococcal coverage 2
• Dicloxacillin is recommended when staphylococcal coverage is desired 2
• Clindamycin 300-450 mg orally four times daily for 5-6 days is recommended for penicillin-allergic patients 2, 3

Treatment Duration

• A 5-day course of antibiotics is as effective as a 10-day course for uncomplicated cellulitis if clinical improvement occurs within the first 5 days 1, 4
• Treatment should be extended if the infection has not improved after 5 days 1
• The 2019 National Institute for Health and Care Excellence (NICE) guideline recommends a course of 5-7 days 1

MRSA Considerations

• MRSA is an unusual cause of typical cellulitis, with standard beta-lactam therapy successful in 96% of cases 1, 2
• Coverage for MRSA is generally not needed for non-purulent cellulitis 5
• Consider MRSA coverage only in specific situations 1, 2, 3:
  • Cellulitis associated with penetrating trauma, especially from illicit drug use
  • Evidence of MRSA infection elsewhere
  • Nasal colonization with MRSA
  • Presence of purulent drainage
  • Systemic inflammatory response syndrome
  • Injection drug use

MRSA Coverage Options (When Indicated)

• Oral options for MRSA coverage include trimethoprim-sulfamethoxazole, doxycycline, or clindamycin 1, 3
• For combination coverage of both streptococci and MRSA, options include clindamycin alone or a combination of trimethoprim-sulfamethoxazole or doxycycline with a beta-lactam 3
• For severe infections requiring parenteral therapy, options include vancomycin, daptomycin, linezolid, or telavancin 1

Adjunctive Measures

• Elevation of the affected area is recommended to promote drainage of edema and inflammatory substances 1, 3
• Treatment of predisposing factors, such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities is recommended 1, 2
• Careful examination of interdigital toe spaces is important as treating fissuring, scaling, or maceration may reduce recurrent infection 1
• Systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) could be considered in nondiabetic adult patients with cellulitis 1

Prevention of Recurrence

• Identify and treat predisposing conditions such as edema, venous insufficiency, tinea pedis, or toe web abnormalities 1, 3
• For patients with 3-4 episodes of cellulitis per year despite addressing predisposing factors, prophylactic antibiotics should be considered 1, 3:
  • Oral penicillin or erythromycin twice daily for 4-52 weeks
  • Intramuscular benzathine penicillin every 2-4 weeks

Clinical Pearls and Pitfalls

• Cellulitis is primarily a clinical diagnosis based on rapidly spreading areas of erythema, swelling, tenderness, and warmth 1, 6
• Cultures of blood, tissue aspirates, or skin biopsies are unnecessary for typical cases of cellulitis 1, 2
• Blood cultures should be obtained only for patients with malignancy, severe systemic features, or unusual predisposing factors 1, 2
• Inflammation may worsen after initiating therapy due to pathogen destruction releasing enzymes that increase local inflammation 1, 2
• It is essential to distinguish cellulitis from purulent collections, as the latter primarily requires drainage rather than antibiotics 1, 2
• Adding trimethoprim-sulfamethoxazole to cephalexin does not improve outcomes in typical cellulitis without abscess 7