What is the appropriate cephalexin (Keflex) dosing for an adult with leg cellulitis and end‑stage renal disease, including adjustments for hemodialysis?

Cephalexin Dosing for Leg Cellulitis in End-Stage Renal Disease

For an adult with leg cellulitis and ESRD on hemodialysis, administer cephalexin 250 mg orally three times weekly immediately after each dialysis session, rather than the standard 500 mg four times daily used in patients with normal renal function. 1

Dosing Principles in ESRD

The fundamental approach is to maintain standard individual doses while extending the dosing interval, not reducing the dose size. 2 This strategy ensures adequate peak serum concentrations to achieve bacterial killing while preventing drug accumulation between dialysis sessions. 3, 4

Specific Regimen

• Dose: 250 mg orally per dialysis session 3
• Frequency: Three times weekly (after each hemodialysis session) 1, 2
• Timing: Always administer immediately post-dialysis to prevent premature drug removal 2

The rationale is that cephalexin is 70-100% renally cleared, and hemodialysis removes approximately 58% of serum cephalexin over 6 hours. 3, 5, 4 In anephric patients, single doses of 250-500 mg produce prolonged serum concentrations with half-lives extending from 6.1 to 18.1 hours compared to 1.1 hours in normal subjects. 3, 4

Why This Dosing Works for Cellulitis

Beta-lactam monotherapy remains the standard of care for typical nonpurulent leg cellulitis, achieving 96% clinical success even in ESRD patients. 1 Cephalexin provides excellent coverage against beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus, the primary pathogens in leg cellulitis. 1

Even with reduced dosing frequency, urinary and tissue concentrations remain adequate because:

• Cephalexin concentrations of 500-1000 mcg/mL in urine follow 250-500 mg oral doses, far exceeding the minimum inhibitory concentration for typical pathogens 3
• Tissue distribution is rapidly achieved despite renal impairment 3
• The drug's stability and low protein binding maintain therapeutic levels 3

Treatment Duration

Treat for 5 days if clinical improvement occurs (warmth and tenderness resolving, erythema improving); extend only if symptoms have not improved within this timeframe. 1 This translates to approximately 2 weeks of calendar time when dosing three times weekly post-dialysis.

When to Add MRSA Coverage

Do NOT routinely add MRSA coverage for typical nonpurulent leg cellulitis in ESRD patients. 1 Add MRSA-active antibiotics ONLY when specific risk factors are present:

• Penetrating trauma or injection drug use 1
• Visible purulent drainage or exudate 1
• Documented MRSA colonization or prior MRSA infection 1
• Systemic inflammatory response syndrome (fever >38°C, tachycardia >90 bpm) 1
• Failure to respond to cephalexin after 48-72 hours 1

If MRSA coverage is needed, use clindamycin 300-450 mg orally three times weekly post-dialysis (if local resistance <10%) or vancomycin 15-20 mg/kg IV after each dialysis session. 1

Critical Monitoring

Therapeutic drug monitoring of serum cephalexin concentrations is recommended in ESRD to verify adequate exposure while avoiding accumulation. 2 Measure levels 2 and 6 hours after a timed dose to optimize dosing. 6

Essential Adjunctive Measures

• Elevate the affected leg above heart level for at least 30 minutes three times daily to promote gravity drainage of edema 1
• Examine interdigital toe spaces for tinea pedis and treat if present to reduce recurrence 1
• Address underlying venous insufficiency and lymphedema with compression stockings once acute infection resolves 1

Common Pitfalls to Avoid

• Never reduce the individual dose to 125 mg or similar—this creates subtherapeutic peak concentrations and treatment failure 2
• Never administer cephalexin before dialysis—the drug will be removed before achieving therapeutic effect 2
• Do not reflexively add MRSA coverage simply because the patient has ESRD—MRSA is uncommon in typical cellulitis even in high-prevalence settings 1, 7
• Do not extend treatment to 10-14 days based on residual erythema alone—some inflammation persists after bacterial eradication 1

When to Hospitalize

Admit ESRD patients with leg cellulitis if any of the following are present:

• Systemic inflammatory response syndrome (SIRS) 1
• Hypotension or hemodynamic instability 1
• Altered mental status or confusion 1
• Concern for necrotizing fasciitis (severe pain out of proportion to exam, skin anesthesia, rapid progression, "wooden-hard" tissues) 1

For hospitalized ESRD patients requiring IV therapy, use vancomycin 15-20 mg/kg IV after each dialysis session (targeting trough 15-20 mg/L) or cefazolin 2 g IV after each dialysis session. 1