What is the best antibiotic for cellulitis?

Best Antibiotic Treatment for Cellulitis

For non-purulent cellulitis, a cephalosporin (such as cephalexin), penicillin, or clindamycin for 5-6 days is the first-line treatment, with coverage primarily targeting streptococci. 1

Antibiotic Selection Algorithm

1. Determine Type of Cellulitis

• Non-purulent cellulitis (most common):

  • First-line: Beta-lactams (cephalexin 500mg PO QID or dicloxacillin 500mg PO QID) 1
  • Alternative for penicillin-allergic patients: Clindamycin 300-450mg PO TID 1, 2

• Purulent cellulitis (with drainage/abscess):

  • First-line: Antibiotics with MRSA coverage
  • Options include:
    • Clindamycin 300-450mg PO TID 1
    • Trimethoprim-sulfamethoxazole 1-2 DS tablets PO BID 1
    • Doxycycline 100mg PO BID 1
    • Linezolid 600mg PO BID (more expensive option) 1, 3

2. Consider Risk Factors for MRSA

Add MRSA coverage if any of the following are present:

• Purulent drainage
• Prior MRSA infection or colonization
• Injection drug use
• Systemic inflammatory response syndrome (SIRS)
• Penetrating trauma
• Evidence of MRSA infection elsewhere
• Nasal colonization with MRSA 1, 4

3. Duration of Therapy

• 5-6 days for uncomplicated cellulitis in patients able to self-monitor 1
• Consider extending treatment if infection has not improved after 5 days 1, 4

Evidence-Based Rationale

The 2021 American College of Physicians guidelines recommend a 5-6 day course of antibiotics active against streptococci for non-purulent cellulitis 1. This recommendation is supported by multiple studies showing similar efficacy between shorter and longer courses of antibiotics.

A randomized controlled trial comparing 5 days versus 10 days of levofloxacin for uncomplicated cellulitis found no significant difference in clinical outcomes, with a 98% success rate in both groups 5. The DANCE trial comparing 6 days versus 12 days of flucloxacillin also found similar cure rates 1.

For non-purulent cellulitis, beta-lactams remain the first choice as they target the most common causative pathogens, primarily beta-hemolytic streptococci 1. The IDSA guidelines specifically recommend cephalexin, dicloxacillin, or other beta-lactams as first-line therapy 1.

Special Considerations

MRSA Coverage

While MRSA coverage is not routinely needed for typical non-purulent cellulitis, it should be considered in specific circumstances. A 2010 study found higher success rates with trimethoprim-sulfamethoxazole (91%) compared to cephalexin (74%) in areas with high MRSA prevalence 6. However, two randomized trials found no benefit to adding trimethoprim-sulfamethoxazole to cephalexin for uncomplicated cellulitis 7, 8.

Severe Infections

For complicated or severe infections, intravenous therapy may be required:

• Vancomycin 15-20 mg/kg/dose IV every 8-12 hours
• Linezolid 600 mg IV/PO BID
• Daptomycin 4 mg/kg/dose IV daily 1

Monitoring and Follow-up

• Monitor daily until improvement
• If no improvement after 48-72 hours, reassess diagnosis and consider changing antibiotics 4
• Address predisposing factors such as edema, obesity, or underlying skin conditions to prevent recurrence 4

Common Pitfalls to Avoid

• Overuse of broad-spectrum antibiotics for typical non-purulent cellulitis
• Unnecessary MRSA coverage for typical cellulitis when risk factors are absent
• Inadequate duration of therapy
• Failure to elevate the affected area to reduce edema
• Overlooking underlying conditions that may contribute to cellulitis 4

In summary, for most cases of non-purulent cellulitis, a 5-6 day course of a beta-lactam antibiotic targeting streptococci is the optimal treatment. Reserve MRSA coverage for specific risk factors or purulent infections.