Treatment of Mild-to-Moderate Cellulitis in Healthy Adults
For an otherwise healthy adult with mild-to-moderate cellulitis, prescribe a beta-lactam antibiotic—specifically cephalexin 500 mg orally every 6 hours or dicloxacillin 250–500 mg orally every 6 hours—for exactly 5 days if clinical improvement occurs; do not add MRSA coverage unless specific risk factors are present. 1, 2
First-Line Antibiotic Selection
Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, achieving approximately 96% clinical success because the primary pathogens are beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus (MSSA). 2, 3
Recommended oral agents include:
All of these agents provide excellent streptococcal and MSSA coverage and are equally effective for typical cellulitis. 1, 2
Treatment Duration: 5 Days Is Sufficient
Treat for exactly 5 days if clinical improvement is evident (reduced warmth, tenderness, improving erythema, absence of fever); extend only if symptoms have not improved within this timeframe. 1, 2
High-quality randomized controlled trial evidence demonstrates that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis, with 98% clinical resolution at 14 days and no relapses by 28 days. 2
Traditional 7–14-day regimens are unnecessary for uncomplicated cases and promote antimicrobial resistance without improving outcomes. 1, 2
When to Add MRSA Coverage (and When NOT To)
MRSA Coverage Is NOT Routinely Necessary
MRSA is an uncommon cause of typical nonpurulent cellulitis even in high-prevalence settings, and routine MRSA coverage provides no additional benefit in 96% of cases. 2, 4, 5
Do not reflexively add MRSA-active antibiotics for typical cellulitis without specific risk factors, as this represents overtreatment and drives resistance. 1, 2
Add MRSA Coverage ONLY When These Risk Factors Are Present:
- Penetrating trauma (e.g., puncture wound, laceration) or injection drug use 1, 2
- Visible purulent drainage or exudate at the infection site 1, 2
- Known MRSA colonization (nasal or other site) or prior MRSA infection 1, 2
- Systemic inflammatory response syndrome (SIRS): fever >38°C, heart rate >90 bpm, respiratory rate >24 breaths/min, or altered mental status 1, 2
- Failure to respond to beta-lactam therapy after 48–72 hours 1, 2
MRSA-Active Regimens When Indicated:
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, 2
Trimethoprim-sulfamethoxazole (TMP-SMX) 1–2 double-strength tablets twice daily PLUS a beta-lactam (cephalexin or amoxicillin) ensures dual coverage; never use TMP-SMX alone because it lacks reliable streptococcal activity. 1, 2
Doxycycline 100 mg orally twice daily PLUS a beta-lactam is another combination option; never use doxycycline alone for typical cellulitis. 1, 2
Hospitalization Criteria
Admit patients when any of the following are present: 1, 6
- Systemic inflammatory response syndrome (SIRS): fever, tachycardia, hypotension, or altered mental status 1, 6
- Signs of deeper or necrotizing infection: severe pain out of proportion to examination, skin anesthesia, rapid progression, "wooden-hard" subcutaneous tissue, bullae, or gas in tissue 1, 2
- Severe immunocompromise or neutropenia 1, 6
- Failure of outpatient therapy after 24–48 hours 1, 6
Essential 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, 2
Examine interdigital toe spaces (for lower-extremity cellulitis) for tinea pedis, fissuring, scaling, or maceration; treating these conditions eradicates colonization and reduces recurrent infection. 1, 2
Address predisposing conditions such as venous insufficiency, lymphedema, chronic edema, obesity, and eczema to minimize recurrence risk. 1, 2
Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in nondiabetic adults only, though evidence is limited. 1, 2
Common Pitfalls to Avoid
Do not add MRSA coverage for typical nonpurulent cellulitis without the specific risk factors listed above; this overtreats 96% of cases and promotes resistance. 1, 2, 5
Do not automatically extend therapy to 7–10 days based on residual erythema alone; extend only if warmth, tenderness, or erythema have not improved after 5 days. 1, 2
Do not use doxycycline or TMP-SMX as monotherapy for typical cellulitis; they lack reliable activity against beta-hemolytic streptococci, the predominant pathogens. 1, 2
Do not obtain blood cultures for uncomplicated cellulitis; they are positive in only ~5% of cases and are unnecessary unless systemic toxicity or severe immunocompromise is present. 1, 3
Do not delay surgical consultation if any signs of necrotizing infection develop (severe pain, rapid progression, bullae, gas, or systemic toxicity). 1, 2
Monitoring and Follow-Up
Reassess patients within 24–48 hours to confirm clinical improvement; oral regimens have reported treatment failure rates of approximately 21% if no response is seen. 2
If no improvement after 48–72 hours of appropriate beta-lactam therapy, consider: