What dose of cefalexin (Keflex) is recommended for cellulitis in a patient with impaired renal function (eGFR 30)?

Cephalexin Dosing for Cellulitis with eGFR 30

For a patient with eGFR 30 mL/min/1.73 m² and cellulitis, reduce the cephalexin dose to 250 mg orally every 6 hours (or 500 mg every 12 hours) for 5 days if clinical improvement occurs. 1, 2

Renal Dose Adjustment Algorithm

The critical threshold for cephalexin dose reduction is creatinine clearance <30 mL/min, making your patient with eGFR 30 right at the boundary requiring careful dosing. 2

• Patients with creatinine clearance <30 mL/min require proportional dose reduction based on the degree of renal impairment 2
• The FDA label states that cephalexin should be administered with caution in markedly impaired renal function, with careful clinical observation and lower-than-usual dosing 1
• In patients with severely impaired renal function, 70-100% of the cephalexin dose is still excreted in urine within 6-8 hours, achieving urinary concentrations of 500-1000 mcg/mL after 250-500 mg doses 2

Standard Cellulitis Treatment Framework

Beta-lactam monotherapy with cephalexin remains the standard of care for typical uncomplicated cellulitis, with a 96% success rate, and MRSA coverage is NOT needed unless specific risk factors are present. 3

• The recommended oral dose for normal renal function is cephalexin 500 mg four times daily for 5 days 3
• Treatment duration is exactly 5 days if clinical improvement occurs, extending only if symptoms have not improved within this timeframe 3
• Do NOT add MRSA coverage (trimethoprim-sulfamethoxazole or doxycycline) for typical nonpurulent cellulitis, as combination therapy provides no additional benefit 3, 4

Practical Dosing Recommendation for eGFR 30

Given the eGFR of 30 mL/min/1.73 m², start with cephalexin 250 mg orally every 6 hours (total 1000 mg/day) rather than the standard 500 mg every 6 hours (2000 mg/day). 2

Alternative acceptable regimen:

• Cephalexin 500 mg orally every 12 hours (also totaling 1000 mg/day) 2

This represents a 50% dose reduction from the standard regimen, which is appropriate for this level of renal function. 2

When MRSA Coverage IS Required

Add MRSA-active therapy ONLY if these specific risk factors are present: 3

• Penetrating trauma or injection drug use
• Purulent drainage or exudate
• Known MRSA colonization or infection elsewhere
• Systemic inflammatory response syndrome (SIRS)

If MRSA coverage is needed, use clindamycin 300-450 mg orally every 6 hours as monotherapy (covers both streptococci and MRSA), avoiding the need for combination therapy 3

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage 3
• Examine interdigital toe spaces for tinea pedis and treat toe web abnormalities to reduce recurrence risk 3
• Address predisposing conditions including venous insufficiency, lymphedema, and chronic edema 3

Monitoring and Follow-Up

Reassess the patient in 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some oral regimens. 3

Signs requiring immediate escalation of care: 3

• Severe pain out of proportion to examination findings
• Rapid progression despite antibiotics
• Systemic toxicity (fever, hypotension, altered mental status)
• Skin anesthesia, bullous changes, or gas in tissue (suggests necrotizing fasciitis)

Common Pitfall to Avoid

Do NOT reflexively add trimethoprim-sulfamethoxazole to cephalexin for typical cellulitis—a landmark randomized trial demonstrated that combination therapy (cephalexin plus trimethoprim-sulfamethoxazole) provided no benefit over cephalexin alone, with clinical cure rates of 83.5% vs 85.5% respectively. 4