How should I manage cellulitis (instead of a genital infection), including appropriate oral antibiotics, MRSA coverage, and criteria for hospital admission?

Management of Cellulitis

For typical nonpurulent cellulitis, prescribe a beta-lactam antibiotic such as cephalexin 500 mg orally every 6 hours or dicloxacillin 250–500 mg every 6 hours for 5 days, extending only if symptoms have not improved within this timeframe. 1

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First-Line Antibiotic Selection

Beta-lactam monotherapy is the standard of care for uncomplicated cellulitis, achieving 96% clinical success because the primary pathogens are beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus. 1 MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings, making routine MRSA coverage unnecessary and potentially harmful by promoting resistance. 1

Recommended Oral Beta-Lactam Options:

• Cephalexin 500 mg orally every 6 hours 1
• Dicloxacillin 250–500 mg orally every 6 hours 1
• Amoxicillin 500 mg orally three times daily 1
• Penicillin V 250–500 mg orally four times daily 1
• Amoxicillin-clavulanate 875/125 mg twice daily (particularly for bite-related cellulitis) 1

For Penicillin-Allergic Patients:

• 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 rates are <10%. 1
• Avoid cephalexin in patients with confirmed immediate-type amoxicillin allergy due to identical R1 side chains, though cross-reactivity between penicillins and cephalosporins is only 2–4%. 1

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Treatment Duration

Treat for exactly 5 days if clinical improvement is evident (resolution of warmth and tenderness, improving erythema, no fever); extend only if symptoms have not improved. 1 High-quality randomized controlled trial evidence demonstrates that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis. 1 Traditional 7–14 day regimens are no longer necessary and represent overtreatment. 1

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When to Add MRSA Coverage

Add MRSA-active antibiotics only when specific risk factors are present. 1 Combination therapy with trimethoprim-sulfamethoxazole plus cephalexin is no more efficacious than cephalexin alone in pure cellulitis without abscess, ulcer, or purulent drainage. 1, 2

MRSA Risk Factors Requiring Coverage:

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate (visible at the infection site) 1
• 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-Active Regimens When Indicated:

• Clindamycin monotherapy 300–450 mg orally every 6 hours (if local resistance <10%) provides coverage for both streptococci and MRSA, avoiding the need for combination therapy. 1
• Trimethoprim-sulfamethoxazole 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 trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis because they lack reliable activity against beta-hemolytic streptococci. 1 Doxycycline must be combined with a beta-lactam when treating typical nonpurulent cellulitis. 1

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Criteria for Hospital Admission

Hospitalize patients with any of the following: 1

• Systemic inflammatory response syndrome (fever, tachycardia, hypotension, altered mental status) 1
• Signs of deeper or necrotizing infection: severe pain out of proportion to examination, skin anesthesia, rapid progression, "wooden-hard" subcutaneous tissues, gas in tissue, or bullous changes 1
• Severe immunocompromise or neutropenia 1
• Failure of outpatient treatment after 24–48 hours with close follow-up 1

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Inpatient IV Antibiotic Regimens

For Uncomplicated Cellulitis Requiring Hospitalization (No MRSA Risk Factors):

• Cefazolin 1–2 g IV every 8 hours (preferred IV beta-lactam) 1
• Oxacillin 2 g IV every 6 hours (alternative) 1

For Complicated Cellulitis with MRSA Risk Factors:

• Vancomycin 15–20 mg/kg IV every 8–12 hours (first-line, A-I evidence) 1
• Linezolid 600 mg IV twice daily (A-I evidence) 1
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 1
• Clindamycin 600 mg IV three times daily (A-III evidence, only if local resistance <10%) 1

For Severe Cellulitis with Systemic Toxicity or Suspected Necrotizing Fasciitis:

Mandatory broad-spectrum combination therapy: 1

• Vancomycin 15–20 mg/kg IV every 8–12 hours plus piperacillin-tazobactam 3.375–4.5 g IV every 6 hours 1
• Alternative combinations: vancomycin or linezolid plus a carbapenem, or ceftriaxone plus metronidazole 1
• For documented group A streptococcal necrotizing fasciitis: penicillin plus clindamycin 1

Treatment duration for severe cellulitis is 7–14 days, individualized based on clinical response, with reassessment at 5 days. 1

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Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances. 1
• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration; treating these eradicates colonization and reduces recurrent infection risk. 1
• Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, eczema, and obesity. 1
• Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited. 1

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Common Pitfalls to Avoid

• Do not routinely add MRSA coverage for typical nonpurulent cellulitis without specific risk factors; this represents overtreatment and increases antibiotic resistance. 1
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 1
• Do not automatically extend therapy to 7–10 days based on residual erythema alone; some inflammation persists even after bacterial eradication. 1
• Do not delay surgical consultation if any signs of necrotizing infection are present, as these infections progress rapidly and require debridement. 1
• Do not continue ineffective antibiotics beyond 48 hours if the infection is progressing; reassess for resistant organisms or deeper infection. 1

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Reassessment and Follow-Up

Reassess patients within 24–48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some oral regimens. 1 If warmth, tenderness, and erythema are improving and the patient is afebrile, stop antibiotics after 5 days. 1 If no improvement is observed, extend treatment and reassess for complications, resistant organisms, or misdiagnosis. 1