What is the recommended dose of cephalexin (cephalexin) for an adult patient with normal renal function and no known allergies, for treating uncomplicated cellulitis?

Cephalexin Dosing for Cellulitis

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

Standard Adult Dosing Regimen

• The FDA-approved dosing for cellulitis is 500 mg every 6 hours (four times daily), which provides adequate tissue concentrations against methicillin-susceptible Staphylococcus aureus (MSSA) and beta-hemolytic streptococci—the primary pathogens in typical cellulitis. 2, 3

• The adult dosage range is 1 to 4 grams daily in divided doses, with 500 mg every 12 hours as an alternative for skin and skin structure infections, though the every-6-hour regimen is preferred for cellulitis. 3

• Cephalexin is completely and rapidly absorbed in the upper intestine, achieving peak serum levels within 1 hour, with 70-100% of the dose excreted unchanged in urine within 6-8 hours. 4

Treatment Duration: The 5-Day Standard

• The Infectious Diseases Society of America establishes 5 days as the recommended duration for uncomplicated cellulitis treatment, with extension beyond 5 days only if the infection has not improved within this timeframe. 1, 2

• High-quality randomized controlled trial evidence demonstrates that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis, eliminating the need for traditional 7-14 day regimens. 1, 2

• Stop antibiotics after 5 days if warmth and tenderness have resolved, erythema is improving, and the patient is afebrile—do not reflexively extend treatment based on residual erythema alone, as some inflammation persists even after bacterial eradication. 1

When Cephalexin Monotherapy Is Appropriate

• Use cephalexin alone for typical nonpurulent cellulitis without drainage, exudate, systemic signs of infection, or MRSA risk factors—beta-lactam monotherapy succeeds in 96% of these cases. 1, 2, 5

• Appropriate scenarios include outpatients without systemic inflammatory response syndrome (SIRS), altered mental status, hemodynamic instability, or evidence of MRSA infection elsewhere. 1, 2

• Cephalexin provides excellent coverage against Streptococcus pyogenes and methicillin-sensitive Staphylococcus aureus, which are the predominant pathogens when organisms are isolated from nonpurulent cellulitis (pathogen isolation rate <20%). 1, 2

Critical Situations Requiring MRSA Coverage Instead

• Do not use cephalexin alone if any of these MRSA risk factors are present: penetrating trauma (especially injection drug use), purulent drainage or exudate, evidence of MRSA infection elsewhere, nasal MRSA colonization, or systemic inflammatory response syndrome. 1, 2

• 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

• The landmark JAMA trial demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin provided no additional benefit for uncomplicated cellulitis without purulent drainage (clinical cure 83.5% vs 85.5%, difference -2.0%, 95% CI -9.7% to 5.7%). 5

Pediatric Dosing

• For children with mild to moderate cellulitis, administer 25-50 mg/kg/day divided into 4 doses every 6 hours. 2, 3

• For more severe infections or MSSA infections in children, use the higher dose range of 75-100 mg/kg/day divided into 3-4 doses. 2, 3

• For otitis media specifically, clinical studies require 75-100 mg/kg/day in 4 divided doses. 3

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily—this hastens improvement by promoting gravitational drainage of edema and inflammatory substances. 1, 2

• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration, and treat these conditions to eradicate colonization and reduce recurrent infection risk. 1, 2

• Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, and eczema with compression stockings once acute infection resolves. 1, 2

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage for all cellulitis—prospective studies confirm 96% success with beta-lactams like cephalexin for typical nonpurulent cellulitis, even in hospitals with high MRSA prevalence. 1, 2

• Do not extend treatment to 10-14 days based on tradition rather than evidence—this increases antibiotic resistance without improving outcomes in uncomplicated cases. 1

• Do not use cephalexin for infections requiring Gram-negative coverage, as it has poor activity against Haemophilus influenzae, Moraxella catarrhalis, and no activity against Pseudomonas. 2

• Assess for abscess with ultrasound if there is any clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics, not cephalexin alone. 1

Renal Dosing Considerations

• For patients with creatinine clearance >50 mL/min (including 59 mL/min), no dose adjustment is needed—use the standard 500 mg every 6 hours. 1

• Patients with creatinine clearance <30 mL/min require dose reduction proportional to reduced renal function, as cephalexin is primarily eliminated through renal excretion (70-100% unchanged in urine). 4, 6

• In anephric patients, single doses of 250-500 mg result in high, prolonged serum concentrations with peak levels within 1 hour, though delayed absorption up to 12 hours can occur. 6