What are the recommended cephalosporins (e.g. cefazolin, ceftriaxone) for treating cellulitis?

Recommended Cephalosporins for Treating Cellulitis

First-generation cephalosporins, particularly cefazolin (IV) and cephalexin (oral), are the recommended cephalosporins for treating non-purulent cellulitis, as they effectively target beta-hemolytic streptococci which are the predominant causative pathogens. For purulent cellulitis or when MRSA is suspected, alternative antibiotics should be considered.

Classification of Cellulitis and Antibiotic Selection

Non-purulent Cellulitis (Most Common)

• First-line IV therapy: Cefazolin 1-2g IV every 8 hours 1, 2
• First-line oral therapy: Cephalexin 500mg orally 4 times daily 1, 2
• Duration: 5-10 days, depending on clinical response 1, 2

Purulent Cellulitis (MRSA Suspected)

• Cephalosporins are not recommended as monotherapy
• Consider MRSA-active agents: vancomycin, linezolid, clindamycin, or TMP-SMX 1

Specific Cephalosporin Options and Dosing

Intravenous Options:

1. Cefazolin:

   • Adult dosing: 1-2g IV every 8 hours 1
   • Pediatric dosing: 100 mg/kg/day divided every 8 hours, not to exceed adult dose 1
   • Advantages: Narrow spectrum, cost-effective, excellent activity against streptococci and methicillin-susceptible S. aureus

2. Ceftriaxone:

   • Adult dosing: 1-2g IV once daily 3
   • Pediatric dosing: 50-75 mg/kg/day (not to exceed 2g/day) 3
   • Advantages: Once-daily dosing convenient for outpatient parenteral therapy

Oral Options:

1. Cephalexin:
   • Dosing: 500mg orally 4 times daily 1, 2
   • First-line for outpatient management of non-purulent cellulitis

Clinical Pearls and Considerations

Efficacy Evidence

• Cefazolin (2g IV daily) plus oral probenecid (1g) has been shown to be equivalent to once-daily ceftriaxone for moderate-to-severe cellulitis, with clinical cure rates of 86% vs. 96% respectively 4
• Twice-daily cefazolin (2g IV) has demonstrated high efficacy with cure rates >90% in home-based treatment of cellulitis 5

Risk Factors for Treatment Failure

• Patients with chronic venous disease have higher failure rates (53%) when treated with cefazolin 6
• Advanced age, elevated C-reactive protein levels, diabetes mellitus, and concurrent bloodstream infection are associated with longer treatment duration 7

Duration of Therapy

• Standard duration: 5 days for uncomplicated cases 2
• Extended treatment (10-14 days) for:
  • Immunocompromised patients
  • Diabetic patients
  • Severe infections
  • Slow clinical response 2, 7

When to Consider Alternative Antibiotics

• If MRSA is suspected (purulent drainage, penetrating trauma, or concurrent MRSA infection elsewhere) 1, 2
• For patients with penicillin allergy: clindamycin is recommended 2
• When treatment with first-line agents fails 1

Special Situations

Outpatient Parenteral Therapy Options

• Cefazolin 2g IV daily + probenecid 1g orally daily 4
• Cefazolin 2g IV twice daily 5
• Ceftriaxone 1-2g IV daily 3

Combination Therapy

• Adding TMP-SMX to cephalexin does not improve outcomes for non-purulent cellulitis 8
• For severe infections or when both streptococci and MRSA coverage is needed, combination therapy may be considered 1

Remember that appropriate dosing is critical for optimal outcomes, and inadequate dosing has been independently associated with clinical failure in patients with cellulitis 2.