What is the recommended treatment for cellulitis using Cephalexin (Cephalosporin) and Doxycycline (Tetracycline)?

Treatment of Cellulitis with Cephalexin and Doxycycline

For uncomplicated cellulitis, cephalexin (500 mg four times daily for 5-7 days) is recommended as first-line therapy, while doxycycline should be reserved for patients with confirmed MRSA infections or penicillin allergies. 1

First-Line Treatment Options

Beta-lactams as Primary Therapy

• Cephalexin (a first-generation cephalosporin) is a preferred first-line agent for cellulitis caused by streptococci and methicillin-sensitive Staphylococcus aureus (MSSA) 1
• Standard dosing: 500 mg four times daily for 5-7 days
• Recent evidence suggests high-dose cephalexin (1000 mg four times daily) may result in fewer treatment failures (3.2% vs 12.9% with standard dose) but with more minor adverse effects 2

When to Consider Doxycycline

• Doxycycline should be considered in the following scenarios:
  • Confirmed or highly suspected MRSA infection
  • Documented beta-lactam allergy
  • Treatment failure with first-line beta-lactam therapy
  • High local prevalence of community-acquired MRSA (CA-MRSA)

Treatment Algorithm Based on Clinical Presentation

Non-purulent Cellulitis (Most Common)

1. First choice: Cephalexin 500 mg four times daily for 5-7 days
2. Alternative if penicillin allergic: Clindamycin or doxycycline

Purulent Cellulitis or Abscess

1. Consider coverage for both streptococci and MRSA:
   • Combination therapy may be warranted (though evidence is mixed)
   • A 2017 study showed no significant benefit of adding trimethoprim-sulfamethoxazole to cephalexin for uncomplicated cellulitis in the per-protocol analysis 3

Severe Infection or Treatment Failure

1. Consider IV antibiotics: Cefazolin, oxacillin, or nafcillin
2. For MRSA coverage: Vancomycin, linezolid, or daptomycin

Important Clinical Considerations

Duration of Therapy

• 5 days of antibiotic treatment is as effective as 10 days for uncomplicated cellulitis 1
• Standard treatment duration: 5-7 days
• May extend to 7-14 days for complicated cases 1

Adjunctive Measures

• Elevate the affected area to promote drainage of edema 1
• Treat underlying conditions (tinea pedis, venous eczema, trauma sites) 1
• Consider anti-inflammatory therapy to potentially hasten resolution 4

Common Pitfalls to Avoid

1. Overtreatment with broad-spectrum antibiotics:

   • The IDSA guidelines note that unnecessary use of broad-spectrum antibiotics for cellulitis contributes to antimicrobial resistance 5
   • Most non-purulent cellulitis is caused by beta-hemolytic streptococci, which remain susceptible to beta-lactams

2. Failure to identify and drain abscesses:

   • Always evaluate for abscess with physical examination (and ultrasound if available)
   • Incision and drainage is the primary treatment for abscess, with antibiotics as adjunctive therapy

3. Inadequate follow-up:

   • Patients should be reassessed within 48-72 hours to evaluate response
   • Treatment failure may indicate incorrect diagnosis, presence of abscess, or resistant organisms

4. Missing predisposing factors:

   • Address underlying conditions to prevent recurrence (edema, venous insufficiency, etc.) 1

Special Populations

Facial Cellulitis

• First-line treatment with oral antibiotics active against streptococci and MSSA
• Cephalexin is appropriate for mild cases 1
• Consider MRSA coverage if risk factors present

Recurrent Cellulitis

• Identify and treat predisposing conditions
• Consider prophylactic antibiotics for patients with 3-4 episodes per year 1

By following this evidence-based approach to cellulitis treatment, clinicians can effectively manage most cases while practicing appropriate antibiotic stewardship.