What is the recommended dose of cephalexin (cephalosporin) for a typical adult patient with uncomplicated cellulitis and normal renal function?

Cephalexin Dosing for Cellulitis

For a typical adult with uncomplicated cellulitis and normal renal function, prescribe cephalexin 500 mg orally four times daily (every 6 hours) for 5 days, extending only if clinical improvement has not occurred within this timeframe. 1, 2, 3

Standard Dosing Regimen

• The FDA-approved adult dosage for skin and skin structure infections is 250 mg every 6 hours, with 500 mg every 12 hours as an alternative for uncomplicated cases. 3
• However, the Infectious Diseases Society of America specifically recommends the higher frequency regimen of 500 mg four times daily (every 6 hours) for cellulitis, which provides more consistent drug levels against streptococcal pathogens. 1, 2
• This dosing provides excellent coverage against the primary pathogens: beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus. 2

Treatment Duration

• Treat for exactly 5 days if clinical improvement occurs—defined as resolution of warmth and tenderness, improving erythema, and absence of fever. 1, 2
• Extend treatment beyond 5 days only if the infection has not improved within this initial period. 1, 2
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases, as 5-day courses demonstrate equivalent efficacy to 10-day courses in high-quality randomized trials. 1

When Cephalexin Monotherapy Is Appropriate

• Use cephalexin alone for typical nonpurulent cellulitis without drainage, exudate, or systemic signs. 1, 2
• Beta-lactam monotherapy succeeds in 96% of uncomplicated cellulitis cases, confirming that MRSA coverage is usually unnecessary. 1
• MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings. 1, 2
• A landmark randomized trial demonstrated that adding trimethoprim-sulfamethoxazole (for MRSA coverage) to cephalexin provided no additional benefit for uncomplicated cellulitis. 2, 4

When to Avoid Cephalexin Monotherapy

Do not use cephalexin alone when any of these MRSA risk factors are present: 1, 2

• Penetrating trauma or injection drug use
• Purulent drainage or exudate (even without a drainable abscess)
• Known MRSA colonization or concurrent MRSA infection elsewhere
• Systemic inflammatory response syndrome (SIRS) with fever, tachycardia, or hypotension

For these scenarios, switch to 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

Penicillin Allergy Considerations

• Cephalexin remains appropriate for penicillin-allergic patients EXCEPT those with immediate hypersensitivity reactions (anaphylaxis, urticaria). 2
• Cross-reactivity between penicillins and cephalosporins is only 2-4%, primarily based on R1 side chain similarity rather than the beta-lactam ring itself. 1
• Cephalexin shares identical R1 side chains with amoxicillin, so avoid cephalexin in patients with confirmed immediate-type amoxicillin allergy. 1

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances. 1
• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration—treating these eradicates colonization and reduces recurrent infection risk. 1, 2
• Address predisposing conditions including venous insufficiency, lymphedema, and chronic edema with compression stockings once acute infection resolves. 1, 2

Common Pitfalls to Avoid

• Do not reflexively extend treatment to 7-10 days based on residual erythema alone—some inflammation persists even after bacterial eradication. 1
• Do not add MRSA coverage routinely without specific risk factors—this represents overtreatment and increases antibiotic resistance. 1, 2
• Do not use first-generation cephalosporins like cephalexin for Lyme disease—they are ineffective and should never be used for erythema migrans. 5

Alternative First-Line Agents

If cephalexin is unavailable or contraindicated, alternative oral beta-lactams include: 1, 2

• Penicillin VK 250-500 mg every 6 hours
• Amoxicillin 500 mg three times daily
• Dicloxacillin 500 mg four times daily
• Clindamycin 300-450 mg four times daily (provides both streptococcal and MRSA coverage if local resistance <10%)