What is the first-line treatment for cellulitis with signs of severity, such as hotness, redness, and streaks of blood, in a patient without a penicillin allergy?

First-Line Treatment for Cellulitis Without Penicillin Allergy

For cellulitis with signs of severity (hotness, redness, and lymphangitic streaks) in a patient without penicillin allergy, prescribe cloxacillin (dicloxacillin) 500 mg orally four times daily for 5 days, as this penicillinase-resistant penicillin provides optimal coverage against both streptococci and methicillin-sensitive Staphylococcus aureus. 1, 2

Antibiotic Selection Algorithm

The correct answer is A: Cloxacillin. This is the most appropriate choice among the options provided because:

• Cloxacillin (dicloxacillin) is specifically recommended by the Infectious Diseases Society of America as first-line therapy for cellulitis, providing excellent coverage against both β-hemolytic streptococci (the most common cause) and methicillin-sensitive S. aureus 1, 2

• Penicillin (Option C) is inadequate because it lacks activity against S. aureus, which can cause cellulitis particularly when associated with penetrating trauma, and the presence of lymphangitic streaks suggests a more aggressive infection requiring broader coverage 1

• Erythromycin (Option B) is not recommended as first-line therapy due to increasing macrolide resistance among group A streptococci regionally in the United States 1, 2

• Tetracycline (Option D) is not appropriate as it is not included in any guideline recommendations for typical cellulitis and lacks adequate coverage against the primary pathogens 1

Dosing and Duration

• Dicloxacillin 500 mg orally four times daily for 5 days is the evidence-based regimen, as 5 days of treatment is as effective as 10-day courses for uncomplicated cellulitis 1, 2

• Cephalexin 500 mg orally four times daily is an equally effective alternative first-generation cephalosporin if dicloxacillin is unavailable 2

When to Escalate to Parenteral Therapy

• Switch to intravenous therapy only if the patient has systemic inflammatory response syndrome, inability to tolerate oral medications, or failed outpatient therapy 2

• For severe cellulitis requiring hospitalization, nafcillin or cefazolin 1-2 g IV every 8 hours are the preferred parenteral agents 1, 2

Understanding the Microbiology

• Most cellulitis cases (85%) are non-culturable, but when organisms are identified, β-hemolytic streptococci (especially group A) are most common, followed by S. aureus 1, 3, 4

• The lymphangitic streaks ("streaks of blood") in this case strongly suggest streptococcal infection, as streptococci cause diffuse, rapidly spreading infection with prominent lymphatic involvement 1

• The source of streptococci in lower extremity cellulitis is frequently the macerated or fissured interdigital toe spaces, emphasizing the importance of examining and treating tinea pedis 1, 2

MRSA Coverage Considerations

• MRSA coverage is NOT indicated for typical cellulitis unless specific risk factors are present, such as injection drug use, prior MRSA infection, athletes, prisoners, military recruits, or residents of long-term care facilities 2, 3, 4

• The presence of lymphangitic streaks alone does not warrant MRSA coverage, as this finding is more consistent with streptococcal infection 1

Essential Adjunctive Measures

• Elevate the affected extremity to promote gravity drainage of edema and inflammatory substances, which accelerates recovery 2

• Examine the toe web spaces carefully for tinea pedis, maceration, or fissures, as these are the reservoir for streptococci in many lower extremity infections 1, 2

• Identify and treat predisposing conditions such as venous stasis dermatitis, lymphedema, or chronic edema to prevent recurrence 2, 3

Common Pitfalls to Avoid

• Do not prescribe unnecessarily broad antibiotics such as vancomycin or dual therapy for typical cellulitis without MRSA risk factors 2

• Do not treat for longer than 5 days unless symptoms have not improved, as longer courses provide no additional benefit for uncomplicated cases 1, 2, 5

• Do not assume oral therapy is inferior to IV therapy for patients who can tolerate oral medications, as oral macrolides have been shown more effective than IV penicillin in some studies, and route of administration does not affect outcomes in patients with similar severity 6, 5

• Do not overlook toe web examination in lower extremity cellulitis, as failing to treat the streptococcal reservoir leads to recurrent infection 1, 2