What is the recommended course of Keflex (cefalexin) for an adult patient with uncomplicated cellulitis?

Keflex Course for Cellulitis

Recommended Treatment Duration and Dosing

For uncomplicated cellulitis, treat with cephalexin (Keflex) 500 mg orally every 6 hours for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1

The standard adult dosing is cephalexin 500 mg four times daily (every 6 hours), which provides excellent coverage against the primary pathogens: beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus 1, 2. This dosing regimen is supported by FDA labeling for skin and skin structure infections 2.

Evidence Supporting 5-Day Duration

• High-quality randomized controlled trial evidence demonstrates that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis 1
• The Infectious Diseases Society of America explicitly recommends 5 days as the standard duration, with extension beyond 5 days only if infection has not improved 1
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1
• Beta-lactam monotherapy (including cephalexin) is successful in 96% of typical cellulitis cases 1

When Standard Cephalexin Monotherapy Is Appropriate

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

• Nonpurulent cellulitis without drainage or exudate 1
• No MRSA risk factors (no penetrating trauma, injection drug use, purulent drainage, or known MRSA colonization) 1, 3
• No systemic inflammatory response syndrome (SIRS) criteria 1
• Ability to self-monitor with close follow-up 1

When to Modify or Avoid Cephalexin Monotherapy

Add MRSA coverage instead of cephalexin alone when specific risk factors are present:

• Penetrating trauma or injection drug use 1, 3
• Purulent drainage or exudate visible 1, 3
• Evidence of MRSA infection elsewhere or known nasal MRSA colonization 1, 3
• Systemic inflammatory response syndrome (fever >38°C, tachycardia >90 bpm, hypotension, altered mental status) 1

For these scenarios, use alternative regimens:

• Clindamycin 300-450 mg orally four times daily (provides single-agent coverage for both streptococci and MRSA, but only if local MRSA clindamycin resistance <10%) 1, 3
• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS a beta-lactam 1, 3
• Doxycycline 100 mg twice daily PLUS a beta-lactam 1

Clinical Decision Algorithm

Day 0 (Initial Presentation):

1. Assess for purulent drainage, abscess (use ultrasound if uncertain), or MRSA risk factors 1
2. If typical nonpurulent cellulitis without risk factors: Start cephalexin 500 mg every 6 hours 1, 2
3. Measure and document extent of erythema, warmth, and tenderness to track progression 1

Days 3-5 (Mandatory Reassessment):

• If warmth and tenderness have resolved, erythema is improving, and patient is afebrile: Stop antibiotics after 5 days 1
• If no improvement in warmth, tenderness, or erythema: Add empiric MRSA coverage immediately (trimethoprim-sulfamethoxazole or clindamycin) and reassess for complications 1
• Treatment failure rates of 21% have been reported with some oral regimens, making this reassessment critical 1

Days 8-10 (If Treatment Extended):

• Reassess for abscess requiring drainage, deep vein thrombosis mimicking cellulitis, or necrotizing infection 1
• Consider hospitalization if systemic signs develop 1

High-Dose Cephalexin Consideration

A pilot randomized controlled trial compared high-dose (1000 mg) to standard-dose (500 mg) cephalexin four times daily for 7 days 4. Treatment failure occurred in 12.9% with standard-dose versus 3.2% with high-dose cephalexin, though high-dose had more minor adverse effects 4. However, current guidelines do not yet recommend routine high-dose cephalexin, and the standard 500 mg four times daily for 5 days remains the evidence-based recommendation 1, 2.

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema 1, 3
• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration; treating these eradicates colonization and reduces recurrent infection 1, 3
• Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, and obesity 1, 3

Common Pitfalls to Avoid

• Do not reflexively extend treatment to 7-10 days based on residual erythema alone, as some inflammation persists even after bacterial eradication 1
• Do not routinely add MRSA coverage for typical cellulitis without specific risk factors, as MRSA is an uncommon cause even in high-prevalence settings 1, 3
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1
• Do not continue ineffective antibiotics beyond 48 hours, as progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection 1

Hospitalization Criteria

Admit patients who have:

• SIRS criteria (fever, altered mental status, hemodynamic instability) 1, 3
• Concern for deeper or necrotizing infection (severe pain out of proportion to exam, skin anesthesia, rapid progression, "wooden-hard" tissues) 1
• Severe immunocompromise or neutropenia 1
• Failure of outpatient treatment after 24-48 hours 1, 3

For hospitalized patients requiring IV therapy: Use cefazolin 1-2 g IV every 8 hours as the preferred IV beta-lactam, or vancomycin 15-20 mg/kg IV every 8-12 hours if MRSA coverage is needed 1.

Renal Dosing Considerations

For patients with GFR ≥59 mL/min, no dose adjustment is needed for cephalexin 500 mg every 6 hours 1, 2. For more severe renal impairment, consult FDA labeling for specific adjustments 2.