What is the recommended treatment for cellulitis?

Treatment of Cellulitis

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

Antibiotic Selection

Mild Nonpurulent Cellulitis (Outpatient)

• Use antibiotics active against streptococci as first-line therapy, including penicillin, amoxicillin, dicloxacillin, cephalexin, or clindamycin 1
• The majority of nonpurulent cellulitis cases are caused by β-hemolytic Streptococcus and methicillin-sensitive S. aureus, not MRSA 2, 3
• Do not routinely add MRSA coverage for typical nonpurulent cellulitis—a randomized controlled trial demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin provided no additional benefit (85% vs 82% cure rates, p=0.66) 4

When to Consider MRSA Coverage

• Reserve MRSA-active antibiotics (trimethoprim-sulfamethoxazole or clindamycin) for purulent cellulitis or patients with specific risk factors: athletes, children in daycare, men who have sex with men, prisoners, military recruits, long-term care facility residents, prior MRSA exposure, or intravenous drug users 2
• In geographic areas with high community-associated MRSA prevalence, empiric MRSA coverage may be considered for moderate to severe cases 5

Moderate to Severe Nonpurulent Cellulitis

• Cover both streptococci and methicillin-susceptible S. aureus with agents like cephalexin or dicloxacillin 1
• Consider hospitalization and intravenous antibiotics for patients with 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—this is sufficient for most cases 1
• Extend treatment only if the infection has not improved within 5 days 1
• This shorter duration represents a shift from traditional 10-14 day courses and reduces unnecessary antibiotic exposure 1

Diagnostic Testing

• Do not routinely obtain cultures (blood or cutaneous aspirates) for typical cellulitis cases 1
• Obtain blood cultures only for: patients with malignancy, severe systemic features (fever, hypotension, tachycardia), or unusual predisposing factors 1
• Cultures are positive in only 15% of cases, making empiric therapy the standard approach 2

Treatment Setting Decision

Outpatient Management

• Treat outpatient if the patient lacks: systemic inflammatory response syndrome, altered mental status, or hemodynamic instability 1
• Most uncomplicated cellulitis can be managed with oral antibiotics in the outpatient setting 6

Hospitalization Indications

• Admit patients with: concern for deeper or necrotizing infection, poor adherence to therapy, severe immunocompromise, or failing outpatient treatment 1
• Hospitalized patients require intravenous antibiotics and closer monitoring 1

Adjunctive Measures

• Elevate the affected extremity to promote gravity drainage of edema and inflammatory substances 1
• Address predisposing factors immediately: edema, obesity, eczema, venous insufficiency, tinea pedis, and toe web abnormalities 1, 6
• Treatment of underlying conditions is critical for preventing recurrence 6

Prevention of Recurrent Cellulitis

• Identify and treat all predisposing conditions at the time of initial diagnosis, as recurrence is common 1, 6
• For patients with 3-4 episodes per year despite treating predisposing factors, initiate prophylactic antibiotics: oral penicillin, oral erythromycin, or intramuscular benzathine penicillin 1
• Antimicrobial prophylaxis can be effective for frequent recurrences 6

Common Pitfalls to Avoid

• Do not overuse MRSA-active antibiotics—the evidence shows no benefit for typical nonpurulent cellulitis, and this contributes to antibiotic resistance 4
• Do not treat for 10-14 days routinely—5 days is sufficient for uncomplicated cases 1
• Consider alternative diagnoses if the patient fails appropriate first-line antibiotics: venous stasis dermatitis, contact dermatitis, eczema, lymphedema, or deeper infections may mimic cellulitis 2, 3
• Do not obtain unnecessary cultures—they are low yield and should be reserved for severe or atypical cases 1