What is the recommended treatment for cellulitis?

Treatment of Cellulitis

For uncomplicated cellulitis, treat with oral antibiotics targeting streptococci (such as cephalexin, amoxicillin, or dicloxacillin) for 5 days, reserving MRSA coverage only for specific high-risk populations or purulent infections. 1

Antibiotic Selection Algorithm

For Mild Nonpurulent Cellulitis (Outpatient)

• Use antibiotics active against streptococci as first-line therapy: penicillin, amoxicillin, dicloxacillin, cephalexin, or clindamycin 1
• Do NOT routinely add MRSA coverage for typical nonpurulent cellulitis 1, 2
• A randomized controlled trial demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin provided no additional benefit (85% vs 82% cure rate, p=0.66) 2

When to Add MRSA Coverage

Reserve MRSA-active antibiotics (trimethoprim-sulfamethoxazole or clindamycin) for:

• Purulent cellulitis 1
• Athletes, children in daycare, men who have sex with men, prisoners, military recruits 3
• Residents of long-term care facilities 3
• Prior MRSA exposure or colonization 3
• Intravenous drug users 3
• Geographic areas with documented high MRSA prevalence (>50% of S. aureus isolates) 4

For Moderate to Severe Cellulitis

• Cover both streptococci and methicillin-susceptible S. aureus (MSSA) 1
• Consider hospitalization if systemic inflammatory response syndrome, altered mental status, hemodynamic instability, or concern for deeper/necrotizing infection 1

Treatment Duration

Treat for 5 days for uncomplicated cellulitis 1

• Extend treatment only if the infection has not improved within 5 days 1
• This shorter duration is supported by both IDSA and American College of Physicians guidelines 1

Diagnostic Testing

Do NOT routinely obtain cultures for typical cellulitis 1

Obtain blood cultures only when:

• Malignancy present 1
• Severe systemic features 1
• Unusual predisposing factors 1
• Immunocompromise 1

This is important because the majority of cellulitis cases are nonculturable, with organisms identified in only 15% of cases 3

Treatment Setting Decision

Outpatient treatment is appropriate when:

• No systemic inflammatory response syndrome 1
• Normal mental status 1
• Hemodynamically stable 1
• Able to adhere to therapy 1

Hospitalize when:

• Concern for deeper or necrotizing infection 1
• Poor adherence anticipated 1
• Severe immunocompromise 1
• Failing outpatient treatment 1

Essential Adjunctive Measures

• Elevate the affected area to promote gravity drainage of edema and inflammatory substances 1
• Treat predisposing factors immediately: edema, obesity, eczema, venous insufficiency, toe web abnormalities (tinea pedis) 1, 5

Prevention of Recurrence

For patients with 3-4 episodes per year despite treating predisposing factors:

• Consider prophylactic antibiotics: oral penicillin, erythromycin, or intramuscular benzathine penicillin 1
• Prophylaxis is only indicated after addressing underlying conditions 5

Common Pitfalls to Avoid

• Do not over-treat with MRSA coverage: The evidence shows no benefit for nonpurulent cellulitis 2, and this contributes to unnecessary antibiotic resistance and costs 3
• Do not treat for longer than necessary: 5 days is sufficient for uncomplicated cases 1
• Do not miss necrotizing infections: Failure to improve with appropriate antibiotics should prompt consideration of resistant organisms, conditions mimicking cellulitis, or deeper infections 3
• Do not ignore predisposing factors: Addressing underlying conditions like tinea pedis and venous insufficiency is critical to prevent recurrence 1, 5