What is the first-line treatment for cellulitis?

First-Line Treatment for Cellulitis

The first-line treatment for cellulitis is an antibiotic active against streptococci, such as penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin, cephalexin, or clindamycin for a 5-day course for typical cases without systemic signs of infection. 1, 2

Antibiotic Selection Based on Presentation

• For uncomplicated, non-purulent cellulitis, oral antibiotics targeting streptococci are recommended as first-line therapy, with preferred options including penicillin, amoxicillin, dicloxacillin, cephalexin, or clindamycin 1, 2
• The Infectious Diseases Society of America recommends these same antibiotics for mild cases of cellulitis, as they effectively target the most common causative organisms 2
• For moderate to severe non-purulent cellulitis, consider coverage for both streptococci and methicillin-susceptible S. aureus (MSSA) 2
• Systemic antibiotics are indicated for all cases of cellulitis, with options including the same antibiotics as for uncomplicated cellulitis, but may require initial IV administration depending on severity 1

Special Considerations for MRSA Coverage

• MRSA coverage is not routinely recommended for non-purulent cellulitis 3
• MRSA coverage should be considered only in specific situations: cellulitis associated with penetrating trauma, evidence of MRSA infection elsewhere, nasal colonization with MRSA, injection drug use, or systemic inflammatory response syndrome (SIRS) 4, 1
• Options for MRSA coverage when indicated include intravenous vancomycin, daptomycin, linezolid, or telavancin, and oral options such as doxycycline, clindamycin, or trimethoprim-sulfamethoxazole 1
• Despite rising rates of community-acquired MRSA, studies have shown that adding trimethoprim-sulfamethoxazole to cephalexin did not improve outcomes in patients with non-purulent cellulitis 5

Duration of Treatment

• A 5-day course of antimicrobial therapy is recommended for uncomplicated cellulitis 4, 1, 2
• Treatment should be extended if the infection has not improved within 5 days 4, 2
• The National Institute for Health and Care Excellence (NICE) guideline recommends a course of 5 to 7 days 4
• Recent studies comparing shorter versus longer courses of antibiotics suggest that shorter courses (5-6 days) are adequate for most cases of uncomplicated cellulitis 4

Treatment Setting Considerations

• Outpatient therapy is appropriate for patients who do not have SIRS, altered mental status, or hemodynamic instability 2
• Hospitalization should be considered for patients with concern for deeper or necrotizing infection, poor adherence to therapy, severe immunocompromise, or failing outpatient treatment 2

Adjunctive Measures

• Elevation of the affected area is recommended to promote gravity drainage of edema and inflammatory substances 2
• Treatment of predisposing factors such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities is important to prevent recurrence 1, 2
• Systemic corticosteroids could be considered in non-diabetic adult patients with cellulitis 1

Common Pitfalls and Caveats

• Cellulitis is often misdiagnosed, with many conditions mimicking its presentation, including venous stasis dermatitis, contact dermatitis, eczema, and lymphedema 3
• Microbiological diagnosis is often unobtainable due to poor sensitivity of culture specimens, making empiric therapy based on likely pathogens necessary 3
• Failure to improve with appropriate first-line antibiotics should prompt consideration for resistant organisms, secondary conditions that mimic cellulitis, or underlying complicating conditions 6
• Despite the increasing prevalence of MRSA in skin infections, empiric MRSA coverage is not routinely recommended for non-purulent cellulitis unless specific risk factors are present 3