What is the recommended dosing of cephalexin for an adult patient with mild to moderate cellulitis, normal renal function, and no severe allergies to penicillins or cephalosporins?

Cephalexin Dosing for Cellulitis in Adults

For an adult with uncomplicated cellulitis and normal renal function, prescribe cephalexin 500 mg orally four times daily for 5 days, extending only if clinical improvement has not occurred within this timeframe. 1, 2

Standard Dosing Regimen

• Cephalexin 500 mg orally every 6 hours (four times daily) is the guideline-recommended dose for typical nonpurulent cellulitis in adults 1, 3
• The FDA-approved adult dosage for skin and soft tissue infections ranges from 1-4 grams daily in divided doses, with 500 mg every 12 hours as an alternative for uncomplicated cases 3
• Treatment duration is 5 days if clinical improvement occurs—extending to 7-10 days only if symptoms persist or worsen 2, 4

Evidence Supporting This Regimen

• Beta-lactam monotherapy (including cephalexin) achieves 96% success rates in typical cellulitis, confirming MRSA coverage is usually unnecessary 2
• Five-day courses are equally effective as 10-day courses for uncomplicated cellulitis, based on high-quality randomized controlled trial evidence 2
• Cephalexin provides excellent coverage against the primary pathogens: beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus 1, 5

When Standard Dosing Is Appropriate

Use cephalexin 500 mg four times daily when the patient has:

• Nonpurulent cellulitis without drainage or exudate 1, 2
• No MRSA risk factors (no penetrating trauma, injection drug use, known MRSA colonization, or purulent drainage) 2, 5
• No systemic inflammatory response syndrome (SIRS) (fever >38°C, tachycardia >90 bpm, tachypnea >24 breaths/min, WBC >12,000 or <4,000) 1
• Ability to self-monitor with close follow-up 2

When to Modify or Avoid Cephalexin

Add MRSA coverage instead of cephalexin monotherapy when:

• Penetrating trauma or injection drug use is present 2, 5
• Purulent drainage or exudate is visible 1, 2
• Evidence of MRSA infection elsewhere or known nasal MRSA colonization exists 2, 4
• SIRS criteria are present 1, 2
• Patient has failed initial beta-lactam therapy after 48-72 hours 5

For these scenarios, use clindamycin 300-450 mg orally four times daily (covers both streptococci and MRSA), or combine trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS a beta-lactam 1, 2, 5

Hospitalize and use IV antibiotics when:

• Systemic toxicity, hypotension, or altered mental status is present 2, 5
• Concern for necrotizing fasciitis exists (severe pain out of proportion, rapid progression, skin anesthesia, bullous changes) 2
• Severe immunocompromise or neutropenia is present 2
• Outpatient therapy has failed after 24-48 hours 5

High-Dose Cephalexin Consideration

• Cephalexin 1000 mg orally four times daily may reduce treatment failure rates (3.2% vs 12.9% with standard dosing) but causes more minor adverse effects, primarily gastrointestinal 6
• Reserve high-dose cephalexin for patients with moderate-to-severe cellulitis, obesity, or those at higher risk for treatment failure 6
• This higher dose remains within the FDA-approved range of 1-4 grams daily 3

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema 2, 5
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration—treating these eradicates colonization and reduces recurrence 2, 4
• Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, and obesity 2, 5

Monitoring and Follow-Up

• Reassess within 24-48 hours to verify clinical improvement (reduced warmth, tenderness, and erythema) 2, 5
• If no improvement or worsening occurs, switch to MRSA-active therapy (vancomycin 15-20 mg/kg IV every 8-12 hours for hospitalized patients, or clindamycin for outpatients) 2, 5
• Blood cultures are positive in only 5% of cases and are unnecessary for typical cellulitis 5

Common Pitfalls to Avoid

• Do not routinely add MRSA coverage for typical nonpurulent cellulitis without specific risk factors—this represents overtreatment and increases resistance 2, 5
• Do not automatically extend treatment to 10-14 days based on residual erythema alone, as some inflammation persists even after bacterial eradication 2
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 2, 5
• Do not delay switching therapy beyond 48-72 hours if treatment failure is evident—progression despite appropriate therapy indicates resistant organisms or deeper infection 5

Renal Dosing

• For GFR ≥59 mL/min (as in this patient with normal renal function), no dose adjustment is needed for cephalexin 500 mg four times daily 2
• For GFR 10-50 mL/min, reduce to 250-500 mg every 8-12 hours 3
• For GFR <10 mL/min, reduce to 250-500 mg every 12-24 hours 3