What is the appropriate treatment for uncomplicated cellulitis using Keflex (cephalexin) and doxycycline?

Treatment of Uncomplicated Cellulitis with Cephalexin and Doxycycline

For uncomplicated cellulitis, cephalexin 500 mg orally 3-4 times daily for 5 days is the recommended first-line treatment, with doxycycline being an alternative option when MRSA coverage is needed. 1

First-Line Treatment for Uncomplicated Cellulitis

Cephalexin (Keflex)

• Dosage: 500 mg orally 3-4 times daily
• Duration: 5-6 days 1
• Target organisms: Primarily effective against Streptococcus pyogenes and methicillin-susceptible Staphylococcus aureus (MSSA) 2
• Indication: FDA-approved for skin and skin structure infections caused by Staphylococcus aureus and/or Streptococcus pyogenes 2

When to Consider Doxycycline

Doxycycline should be considered when MRSA coverage is needed, particularly in patients with:

• Prior MRSA infection
• Recent hospitalization
• Antibiotic use in the past 3 months
• Close contact with MRSA-infected individuals
• Penetrating trauma
• Evidence of MRSA infection elsewhere
• MRSA nasal colonization
• Injection drug use
• Systemic inflammatory response syndrome (SIRS) 1

Evidence Supporting Treatment Recommendations

Treatment Duration

• 5 days of antibiotic therapy is sufficient for uncomplicated cellulitis 1, 3
• A randomized controlled trial showed no significant difference in clinical outcomes between 5 days and 10 days of therapy (98% success rate in both groups) 3
• Treatment should be extended if the infection has not improved within 5 days 1

MRSA Coverage

• For nonpurulent cellulitis (without abscess or purulent drainage), beta-hemolytic streptococci are the predominant pathogens, and MRSA coverage is generally not necessary 4, 5
• A randomized controlled trial found that adding trimethoprim-sulfamethoxazole (TMP-SMX) to cephalexin did not significantly improve outcomes for uncomplicated cellulitis in the per-protocol analysis 6
• However, in areas with high MRSA prevalence, antibiotics with MRSA activity showed higher success rates compared to cephalexin alone 7

Treatment Algorithm for Uncomplicated Cellulitis

1. Initial Assessment:

   • Determine if the cellulitis is purulent (with abscess or drainage) or nonpurulent
   • Assess for MRSA risk factors
   • Check for signs of systemic illness or severe infection

2. For Nonpurulent Cellulitis without MRSA Risk Factors:

   • First choice: Cephalexin 500 mg orally 3-4 times daily for 5 days 1

3. For Nonpurulent Cellulitis with MRSA Risk Factors:

   • Consider doxycycline as an alternative
   • Or use cephalexin plus an MRSA-active agent if severe or extensive

4. For Purulent Cellulitis:

   • MRSA coverage is recommended (doxycycline would be appropriate)

5. Follow-up Assessment:

   • Evaluate response after 48-72 hours
   • If not improving, consider:
     • Extending treatment duration
     • Changing antibiotics based on likely pathogens and local resistance patterns
     • Assessing for complications or underlying conditions

Common Pitfalls and Caveats

• Inadequate treatment duration: While 5 days is typically sufficient, treatment should be extended if the infection has not improved 1
• Failure to address predisposing factors: Treat underlying conditions that may contribute to cellulitis 1
• Inappropriate MRSA coverage: Routine MRSA coverage is not necessary for all cases of nonpurulent cellulitis 4, 5
• Missing signs of deeper infection: Patients with SIRS, altered mental status, hemodynamic instability, or signs of deeper infection should be admitted for IV antibiotics 1
• Cross-reactivity concerns: Patients with immediate (anaphylactic-type) hypersensitivity to penicillin may have up to 10% cross-reactivity with cephalexin 1

Adjunctive Measures

• Elevation of the affected area to reduce edema
• Treatment of predisposing factors (edema, underlying skin disorders)
• Careful examination and treatment of interdigital toe spaces
• Maintaining good personal hygiene 1