What is the recommended antibiotic therapy for an adult with purulent cellulitis of the leg?

Purulent Cellulitis of the Leg: Antibiotic Recommendations

For purulent cellulitis of the leg, you must provide MRSA-active antibiotic therapy; the preferred oral regimen is clindamycin 300–450 mg every 6 hours for 5 days, provided local MRSA clindamycin resistance is <10%. 1

Why MRSA Coverage Is Mandatory for Purulent Cellulitis

Purulent cellulitis—defined by visible drainage, exudate, or associated abscess—requires empiric MRSA coverage because Staphylococcus aureus is the predominant pathogen, with 50% of isolates being methicillin-resistant in purulent cases. 2 The presence of purulence is itself a positive predictor of MRSA (odds ratio 5.188). 2 This stands in stark contrast to typical non-purulent cellulitis, where beta-hemolytic streptococci cause the vast majority of cases and beta-lactam monotherapy achieves 96% success. 1, 3, 4

First-Line Oral Antibiotic Options

Clindamycin Monotherapy (Preferred)

• Clindamycin 300–450 mg orally every 6 hours for 5 days provides single-agent coverage for both streptococci and MRSA, eliminating the need for combination therapy. 1, 5
• Critical caveat: Use clindamycin only if your local MRSA clindamycin resistance rate is <10%; higher resistance rates make this agent inappropriate. 1
• Clindamycin carries a higher risk of Clostridioides difficile infection compared to other oral agents. 1

Combination Therapy Alternatives

If clindamycin resistance exceeds 10% or the patient cannot tolerate clindamycin, use combination therapy:

• Trimethoprim-sulfamethoxazole (TMP-SMX) 1–2 double-strength tablets twice daily PLUS a beta-lactam (cephalexin 500 mg four times daily OR amoxicillin 500 mg three times daily) for 5 days. 1, 5

  • TMP-SMX alone is inadequate because it lacks reliable activity against beta-hemolytic streptococci. 1, 5
  • Contraindicated in third-trimester pregnancy and infants <2 months. 1

• Doxycycline 100 mg orally twice daily PLUS a beta-lactam (same options as above) for 5 days. 1, 5

  • Doxycycline monotherapy is never appropriate for cellulitis because it does not reliably cover streptococci. 1
  • Absolutely contraindicated in children <8 years (tooth discoloration, bone growth impairment) and pregnancy (category D). 1

Linezolid (Reserve for Complicated Cases)

• Linezolid 600 mg orally twice daily for 5 days covers both streptococci and MRSA but is significantly more expensive than other options. 1, 5
• Reserve for patients who cannot tolerate first-line agents or have documented resistance. 5

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs (resolution of warmth/tenderness, improving erythema, no fever); extend only if symptoms have not improved. 1, 6 High-quality randomized controlled trial evidence demonstrates that 5-day courses are as effective as 10-day courses for uncomplicated purulent cellulitis. 1 Traditional 7–14-day regimens are unnecessary and promote antimicrobial resistance. 1

Intravenous Therapy for Severe or Hospitalized Cases

If the patient requires hospitalization due to systemic toxicity, inability to tolerate oral medications, or severe immunocompromise:

• Vancomycin 15–20 mg/kg IV every 8–12 hours (target trough 15–20 mg/L) is first-line IV therapy with A-I level evidence. 1
• Alternative IV agents (all A-I evidence): linezolid 600 mg IV twice daily, daptomycin 4 mg/kg IV once daily. 1
• Clindamycin 600 mg IV every 8 hours is an option only if local MRSA resistance is <10% (A-III evidence). 1
• Duration for complicated infections is 7–14 days, individualized by clinical response. 1

For severe cellulitis with systemic toxicity or suspected necrotizing infection, use vancomycin PLUS piperacillin-tazobactam 3.375–4.5 g IV every 6 hours to provide broad-spectrum polymicrobial coverage. 1

Critical Pitfalls to Avoid

• Never use beta-lactams alone (cephalexin, dicloxacillin, amoxicillin) for purulent cellulitis—they lack MRSA activity and will fail. 1
• Never use doxycycline or TMP-SMX as monotherapy for any cellulitis—they do not reliably cover streptococci, which may still be present even in purulent cases. 1, 5
• Do not reflexively add MRSA coverage to non-purulent cellulitis—MRSA is uncommon in typical non-purulent cases even in high-prevalence settings, and beta-lactam monotherapy achieves 96% success. 1, 3, 4
• Do not continue ineffective antibiotics beyond 48–72 hours—lack of improvement indicates resistant organisms, undrained abscess, or deeper infection requiring reassessment. 1

Adjunctive Measures

• Elevate the affected leg above heart level for 30 minutes three times daily to promote gravity drainage of edema and inflammatory mediators. 1
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration and treat if present to reduce recurrence risk. 1
• Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, and obesity. 1, 3
• If an abscess is present, incision and drainage is the primary treatment—antibiotics play only a subsidiary role for purulent collections. 1

When to Hospitalize

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

• Systemic inflammatory response syndrome (fever >38°C, tachycardia >90 bpm, 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