What are the first-line antibiotic treatments for cellulitis?

First-Line Antibiotic Treatments for Cellulitis

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

Antibiotic Selection Based on Presentation

Uncomplicated Cellulitis (Mild, Non-Purulent)

• Oral antibiotics active against streptococci are recommended as first-line therapy 1
• Preferred options include:
  • Penicillin 1
  • Amoxicillin 1
  • Amoxicillin-clavulanate 1
  • Dicloxacillin 1
  • Cephalexin 1
  • Clindamycin 1
• Duration of therapy should be 5 days, with extension if infection has not improved within this period 1, 2

Cellulitis with Systemic Signs (Moderate Non-Purulent)

• Systemic antibiotics are indicated 1
• Many clinicians include coverage against methicillin-susceptible S. aureus (MSSA) 1
• Options include the same antibiotics as for uncomplicated cellulitis, but may require initial IV administration depending on severity 1

Special Circumstances Requiring MRSA Coverage

• MRSA coverage should be considered in cellulitis associated with: 1
  • Penetrating trauma
  • Evidence of MRSA infection elsewhere
  • Nasal colonization with MRSA
  • Injection drug use
  • Systemic inflammatory response syndrome (SIRS)
• Options for MRSA coverage include: 1
  • Intravenous: vancomycin, daptomycin, linezolid, or telavancin
  • Oral: doxycycline, clindamycin, or trimethoprim-sulfamethoxazole (SMX-TMP)

Severely Compromised Patients

• Broad-spectrum antimicrobial coverage may be considered 1
• Recommended empiric regimen: vancomycin plus either piperacillin-tazobactam or imipenem/meropenem 1

Duration of Treatment

• 5-day course is recommended for uncomplicated cellulitis 1, 2
• Treatment should be extended if the infection has not improved within 5 days 1, 2
• Recent studies show that 5-6 days of therapy is as effective as longer courses (10-12 days) if clinical improvement occurs 1, 2, 3

Important Considerations

Microbiology

• Most cases of cellulitis are caused by β-hemolytic Streptococcus and Staphylococcus aureus 4, 5
• MRSA is an unusual cause of typical cellulitis, with studies showing successful treatment with β-lactams in 96% of patients 1
• In areas with high MRSA prevalence, treatment success rates may be higher with trimethoprim-sulfamethoxazole or clindamycin compared to cephalexin 6

Adjunctive Measures

• Elevation of the affected area is recommended to hasten improvement 1
• Treatment of predisposing factors (edema, obesity, eczema, venous insufficiency, toe web abnormalities) is important 1
• For lower-extremity cellulitis, careful examination of interdigital toe spaces is recommended 1
• Systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) could be considered in non-diabetic adult patients 1

Outpatient vs. Inpatient Treatment

• Outpatient therapy is recommended for patients who do not have SIRS, altered mental status, or hemodynamic instability 1
• Hospitalization should be considered for: 1
  • Concern for deeper or necrotizing infection
  • Poor adherence to therapy
  • Severely immunocompromised patients
  • Failing outpatient treatment

Common Pitfalls

• Treating for MRSA when not indicated - MRSA is an unusual cause of typical cellulitis 1, 5
• Using combination therapy (SMX-TMP plus cephalexin) for pure cellulitis - studies show this is no more effective than cephalexin alone 1
• Extending treatment unnecessarily - 5 days is sufficient for uncomplicated cellulitis if clinical improvement occurs 1, 2
• Failing to address predisposing factors, which can lead to recurrence 1
• Missing clinical mimickers of cellulitis such as venous stasis dermatitis, contact dermatitis, eczema, and lymphedema 5