Prescription for Uncomplicated Lower Limb Cellulitis
For an otherwise healthy adult with uncomplicated lower‑leg cellulitis, prescribe cephalexin 500 mg orally every 6 hours for 5 days, extending only if warmth, tenderness, or erythema have not improved by day 5.
First‑Line Oral Antibiotic Regimen
Cephalexin 500 mg orally every 6 hours (four times daily) for 5 days is the preferred oral beta‑lactam, providing excellent coverage against beta‑hemolytic streptococci (especially Streptococcus pyogenes) and methicillin‑sensitive Staphylococcus aureus, the primary pathogens in typical cellulitis 1.
Alternative oral beta‑lactams with equivalent efficacy include:
Beta‑lactam monotherapy achieves approximately 96% clinical success in typical non‑purulent cellulitis, confirming that MRSA coverage is usually unnecessary 1, 2.
Treatment Duration
Treat for exactly 5 days if clinical improvement occurs (resolution of warmth and tenderness, improving erythema, afebrile); extend only if symptoms have not improved within this timeframe 1, 3, 4.
High‑quality randomized controlled trial evidence demonstrates that 5‑day courses are as effective as 10‑day courses, with 98% clinical resolution at 14 days and no relapses by 28 days 1, 4.
Traditional 7–14‑day regimens are no longer necessary for uncomplicated cases and promote unnecessary antibiotic resistance 1.
When to Add MRSA Coverage (and When NOT to)
MRSA is an uncommon cause of typical cellulitis even in high‑prevalence settings, so routine MRSA coverage is unnecessary 1, 2.
Add MRSA‑active antibiotics ONLY when specific risk factors are present 1, 3:
- Penetrating trauma or injection drug use
- Visible purulent drainage or exudate
- Known MRSA colonization or prior MRSA infection
- Systemic inflammatory response syndrome (fever >38°C, heart rate >90 bpm, respiratory rate >24 breaths/min)
- Lack of clinical response to beta‑lactam therapy after 48–72 hours
If MRSA coverage is required, use 1:
- 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 <10%)
- Trimethoprim‑sulfamethoxazole 1–2 double‑strength tablets twice daily PLUS a beta‑lactam (e.g., cephalexin or amoxicillin)
- Doxycycline 100 mg orally twice daily PLUS a beta‑lactam
Essential Adjunctive Measures
Elevate the affected leg above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances, which hastens clinical improvement 1, 5, 3.
Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration and treat these conditions to eradicate colonization and reduce recurrent infection 1.
Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, obesity, and eczema to lower recurrence risk 1, 2, 6.
Hospitalization Criteria
Admit patients with cellulitis when any of the following are present 1, 3:
- Systemic inflammatory response syndrome (fever, tachycardia, hypotension, altered mental status)
- Signs of deeper or necrotizing infection (severe pain out of proportion to examination, skin anesthesia, rapid progression, "wooden‑hard" tissue, gas in tissue, bullous changes)
- Severe immunocompromise or neutropenia
- Failure of outpatient therapy after 24–48 hours
Intravenous Therapy for Hospitalized Patients
For uncomplicated cellulitis requiring hospitalization without MRSA risk factors, use cefazolin 1–2 g IV every 8 hours or nafcillin 2 g IV every 6 hours 1.
For severe cellulitis with systemic toxicity or suspected necrotizing infection, use vancomycin 15–20 mg/kg IV every 8–12 hours PLUS piperacillin‑tazobactam 3.375–4.5 g IV every 6 hours 1, 3.
Treatment duration for complicated infections is 7–14 days, individualized based on clinical response 1.
Common Pitfalls to Avoid
Do not add MRSA coverage routinely for typical non‑purulent cellulitis without the specified risk factors; this overtreats approximately 96% of cases and promotes antimicrobial resistance 1, 2.
Do not automatically extend therapy to 7–10 days based solely on residual erythema; extend only if warmth, tenderness, or erythema have not improved after 5 days 1, 4.
Do not use doxycycline or trimethoprim‑sulfamethoxazole as monotherapy for typical cellulitis, as they lack reliable activity against beta‑hemolytic streptococci, the predominant pathogens 1.
Do not delay surgical consultation if any signs of necrotizing infection are present (severe pain out of proportion, rapid progression, bullae, gas, or necrosis), as these infections progress rapidly and require debridement 1.
Follow‑Up and Reassessment
Reassess patients within 24–48 hours to verify clinical response; treatment failure rates of approximately 21% have been reported with some oral regimens 1.
If no improvement after 48–72 hours of appropriate therapy, consider resistant organisms (MRSA), undrained abscess, deeper infection, or alternative diagnoses 1.
Optional Adjunctive Corticosteroids (Weak Recommendation)
Systemic corticosteroids (prednisone 40 mg daily for 7 days) may be considered in non‑diabetic adults with uncomplicated cellulitis to potentially shorten healing time by approximately one day, though evidence is limited 5, 3.
Do not use corticosteroids in diabetic patients, pregnant women, children, or patients with systemic toxicity, SIRS, or suspected necrotizing infection 5.