What is the recommended dose of cephalexin (Keflex) for treating cellulitis?

Cephalexin Dosing for Cellulitis

For uncomplicated cellulitis in adults, cephalexin 500 mg orally four times daily (every 6 hours) is the recommended dose, with treatment duration of 5 days if clinical improvement occurs. 1, 2, 3

Standard Adult Dosing

• Cephalexin 500 mg orally every 6 hours (four times daily) is the established dose for skin and soft tissue infections including cellulitis 1, 2, 3
• The FDA-approved dosing range for adults is 1-4 grams daily in divided doses, with 500 mg every 6 hours being standard for most infections 3
• This dosing provides adequate tissue concentrations against methicillin-susceptible Staphylococcus aureus (MSSA) and streptococci, the primary pathogens in typical cellulitis 1, 2

Treatment Duration

• A 5-day course is as effective as 10 days if clinical improvement has occurred by day 5 1
• Treatment should be extended beyond 5 days only if the infection has not improved within this timeframe 1
• This shorter duration recommendation is based on strong, high-quality evidence from the IDSA guidelines 1

Pediatric Dosing

• For children with mild to moderate cellulitis: 25-50 mg/kg/day divided into 4 doses 1, 2, 3
• For MSSA infections in children: 75-100 mg/kg/day divided into 3-4 doses 2
• The higher dose range (75-100 mg/kg/day) should be used when MSSA is confirmed or strongly suspected 2

When Cephalexin is Appropriate

Cephalexin monotherapy is appropriate for:

• Typical cellulitis without systemic signs of infection (mild nonpurulent cellulitis) 1
• Patients without risk factors for MRSA 1
• Outpatient management in patients without SIRS, altered mental status, or hemodynamic instability 1

Critical Limitations and When NOT to Use Cephalexin

Do not use cephalexin alone if any of the following are present:

• Penetrating trauma, especially injection drug use 1
• Evidence of MRSA infection elsewhere or nasal MRSA colonization 1
• Systemic inflammatory response syndrome (SIRS): fever >38°C or <36°C, tachycardia >90 bpm, tachypnea >24 breaths/min, or WBC >12,000 or <4,000 cells/µL 1
• Purulent drainage or abscess formation 1

In these scenarios, add MRSA coverage with trimethoprim-sulfamethoxazole, doxycycline, or clindamycin (if using TMP-SMX or doxycycline, continue cephalexin for streptococcal coverage) 1

Emerging Evidence on Higher Dosing

• A 2023 pilot RCT found that cephalexin 1000 mg four times daily had lower treatment failure rates (3.2%) compared to standard 500 mg dosing (12.9%), though with more minor adverse effects 4
• This higher dose is not yet guideline-recommended but may be considered for patients at higher risk of treatment failure 4
• Standard 500 mg dosing remains appropriate for most patients, including morbidly obese individuals (BMI ≥40), as failure rates did not differ significantly by obesity status 5

Adjunctive Measures

Beyond antibiotics, ensure:

• Elevation of the affected extremity to promote drainage of edema 1
• Examination and treatment of interdigital toe spaces for tinea pedis or maceration in lower extremity cellulitis 1
• Treatment of predisposing conditions such as venous insufficiency, eczema, or edema 1

Common Pitfalls to Avoid

• Do not assume MRSA coverage is needed for all cellulitis: A prospective study showed 96% success with beta-lactams like cephalexin, indicating MRSA is uncommon in typical cellulitis 1
• Do not use cephalexin for infections requiring Gram-negative coverage: It has poor activity against Haemophilus influenzae, Moraxella catarrhalis, and no activity against Pseudomonas 2
• Do not continue antibiotics beyond 5 days if clinical improvement has occurred: Longer courses do not improve outcomes 1
• Do not use four-times-daily dosing as an excuse to avoid treatment: The FDA label allows 500 mg every 12 hours for uncomplicated skin infections, though QID dosing is preferred for cellulitis 3