What is the first-line antibiotic treatment for uncomplicated cellulitis of the arm in a healthy adult?

First-Line Antibiotic Treatment for Uncomplicated Arm Cellulitis

For uncomplicated cellulitis of the arm in a healthy adult, prescribe cephalexin 500 mg orally every 6 hours or dicloxacillin 250–500 mg orally every 6 hours for exactly 5 days if clinical improvement occurs. 1

Why Beta-Lactam Monotherapy Is Standard of Care

Beta-lactam monotherapy achieves 96% clinical success in typical non-purulent cellulitis because the primary pathogens are beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus (MSSA). 1, 2 Even in settings with high community MRSA prevalence, MRSA remains an uncommon cause of typical cellulitis without purulent drainage. 1, 3

Recommended Oral Beta-Lactam Options

• Cephalexin 500 mg every 6 hours 1
• Dicloxacillin 250–500 mg every 6 hours 1
• Amoxicillin (alternative) 1
• Amoxicillin-clavulanate 875/125 mg twice daily (provides additional beta-lactamase coverage) 1

Treatment Duration: 5 Days Is Sufficient

Treat for exactly 5 days if warmth, tenderness, and erythema are improving and the patient is afebrile. 1 High-quality randomized controlled trial evidence demonstrates that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis. 1, 4 Extend treatment only if symptoms have not improved within this 5-day window—do not reflexively extend to 7–10 days based on residual erythema alone, as some inflammation persists even after bacterial eradication. 1

When to Add MRSA Coverage (and When NOT To)

Do NOT add MRSA coverage for typical arm cellulitis unless specific risk factors are present. 1, 3 MRSA-active antibiotics are indicated only when any of the following exist:

• Purulent drainage or exudate at the infection site 1
• Penetrating trauma or injection drug use 1, 2
• Known MRSA colonization or prior MRSA infection 1
• Systemic inflammatory response syndrome (fever >38°C, heart rate >90 bpm, respiratory rate >24 breaths/min) 1
• Failure to respond to beta-lactam therapy after 48–72 hours 1

MRSA Coverage Regimens (When Indicated)

If any of the above risk factors are present:

• Clindamycin 300–450 mg orally every 6 hours provides single-agent coverage for both streptococci and MRSA, but use only if local MRSA clindamycin resistance is <10%. 1
• Trimethoprim-sulfamethoxazole (TMP-SMX) 1–2 double-strength tablets twice daily PLUS a beta-lactam (cephalexin or amoxicillin) 1
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam 1

Critical pitfall: Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis—they lack reliable activity against beta-hemolytic streptococci, which cause the vast majority of cases. 1

Penicillin Allergy Considerations

For patients with non-immediate penicillin allergy (e.g., rash without anaphylaxis), cephalexin remains acceptable because cross-reactivity is only 2–4%. 1 However, avoid cephalexin in confirmed immediate-type amoxicillin allergy due to identical R1 side chains. 1

For true penicillin-allergic patients, use:

• Clindamycin 300–450 mg orally every 6 hours (if local MRSA clindamycin resistance <10%) 1

Hospitalization Criteria

Admit patients with arm cellulitis if any of the following are present:

• Systemic inflammatory response syndrome (fever, tachycardia, hypotension, altered mental status) 1
• Signs of necrotizing infection (severe pain out of proportion to exam, skin anesthesia, rapid progression, "wooden-hard" tissue, gas or bullae) 1
• Severe immunocompromise or neutropenia 1
• Failure of outpatient therapy after 24–48 hours 1

Inpatient IV Regimens

• Without MRSA risk factors: Cefazolin 1–2 g IV every 8 hours or nafcillin 2 g IV every 6 hours 1
• Severe cellulitis with systemic toxicity: Vancomycin 15–20 mg/kg IV every 8–12 hours PLUS piperacillin-tazobactam 3.375–4.5 g IV every 6 hours 1

Essential Adjunctive Measures

• Elevate the affected arm above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances. 1
• Treat predisposing conditions such as chronic eczema, venous insufficiency, or lymphedema to reduce recurrence risk. 1

Monitoring and Follow-Up

Re-evaluate within 24–48 hours to confirm improvement, as oral regimens have reported failure rates around 21% if no response is seen. 1 If no improvement after 48–72 hours of appropriate therapy, consider:

• Resistant organisms (MRSA) 1
• Undrained abscess 1
• Deeper infection (septic arthritis, osteomyelitis) 1
• Alternative diagnoses (deep vein thrombosis, gout) 1

Common Pitfalls to Avoid

• Do NOT add MRSA coverage indiscriminately for typical arm cellulitis without specific risk factors—this overtreats ~96% of cases and drives antimicrobial resistance. 1, 5
• Do NOT automatically extend therapy to 7–10 days—extend only if warmth, tenderness, or erythema have not improved after the initial 5-day course. 1
• Do NOT use doxycycline or TMP-SMX as monotherapy for typical cellulitis—they miss streptococcal pathogens in the vast majority of cases. 1
• Do NOT delay surgical consultation if any signs of necrotizing infection are present—timely debridement is critical. 1