What is the first-line treatment for a patient with cellulitis (inflammation of the skin and subcutaneous tissues) presenting with signs of infection, including hotness, redness, and streaks of blood, with no known allergy to penicillin (antibiotic)?

First-Line Treatment for Cellulitis Without Penicillin Allergy

For a patient with cellulitis presenting with hotness, redness, and streaks (lymphangitis) without penicillin allergy, prescribe a penicillinase-resistant penicillin such as dicloxacillin or a first-generation cephalosporin such as cephalexin orally for 5 days. 1

Antibiotic Selection Algorithm

For Typical Cellulitis (No Purulent Drainage or Abscess)

Oral therapy is appropriate for most patients:

• Dicloxacillin 500 mg four times daily provides excellent coverage against both streptococci (the primary cause) and methicillin-sensitive Staphylococcus aureus 1
• Cephalexin 500 mg four times daily is an equally effective alternative first-generation cephalosporin 1
• Both agents target β-hemolytic streptococci, which cause the majority of cellulitis cases, while also covering S. aureus 2, 3

The presence of lymphangitic streaks does not change antibiotic selection - these "streaks of blood" indicate lymphatic involvement, which is typical of streptococcal cellulitis and responds to the same first-line therapy 1

For Severe Cellulitis Requiring Hospitalization

Parenteral therapy is indicated if the patient has:

• Systemic inflammatory response syndrome (fever, tachycardia, hypotension) 4
• Inability to tolerate oral medications 1
• Failed outpatient therapy 4

Intravenous options:

• Nafcillin or cefazolin IV are the preferred agents 1
• Dosing: Cefazolin 1-2 g IV every 8 hours 4

Treatment Duration

5 days of antibiotic therapy is sufficient for uncomplicated cellulitis - this duration is as effective as 10-day courses 1, 4

Extend treatment only if:

• Symptoms have not improved after 5 days 4
• The infection involves deeper structures 1

MRSA Coverage: When NOT Needed

Do NOT routinely cover MRSA in typical cellulitis without purulent drainage 3

MRSA coverage is only indicated if specific risk factors are present:

• Purulent drainage or associated abscess 2
• Injection drug use 1
• Prior MRSA infection 4, 2
• Athletes, prisoners, military recruits, or long-term care residents 2

If MRSA coverage is needed, add:

• Clindamycin 300-450 mg orally three times daily 4
• Trimethoprim-sulfamethoxazole or doxycycline are alternatives 4

Essential Adjunctive Measures

Elevation of the affected extremity is critical and often neglected - this promotes gravity drainage of edema and inflammatory substances, accelerating recovery 1, 4

Identify and treat predisposing conditions:

• Examine interdigital toe spaces for tinea pedis (athlete's foot) or maceration - streptococci often colonize these areas in lower extremity cellulitis 1, 5
• Treat venous stasis dermatitis, lymphedema, or trauma 1, 5

Common Pitfalls to Avoid

Failing to examine toe web spaces in lower extremity cellulitis - this is a frequent source of streptococcal colonization that predisposes to recurrent infection 4, 5

Prescribing unnecessarily broad antibiotics - typical cellulitis is caused by streptococci, not MRSA, and does not require vancomycin or dual therapy 4, 3

Using macrolides (erythromycin, azithromycin) as first-line therapy - macrolide resistance among group A streptococci has increased to 8-9% in the United States, making these agents less reliable 1

Treating for longer than necessary - 5 days is adequate for uncomplicated cases; extending to 10 days provides no additional benefit 1, 4

When Initial Therapy Fails

If the patient does not improve within 48-72 hours, consider:

• Deeper infection (abscess, necrotizing fasciitis) requiring imaging 1
• Resistant organisms (MRSA) - switch to clindamycin or trimethoprim-sulfamethoxazole 4
• Misdiagnosis - many conditions mimic cellulitis including venous stasis dermatitis, contact dermatitis, and deep vein thrombosis 2, 3
• Underlying immunosuppression, chronic liver disease, or chronic kidney disease 2