How is cephalexin (a cephalosporin antibiotic) prescribed for a patient with a bacterial skin infection, considering factors such as age, weight, renal function (e.g. impaired renal function), and history of allergies to penicillin?

Cephalexin Prescribing for Skin Infections

For typical uncomplicated skin infections in adults, 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 Adult Dosing

• The FDA-approved adult dosage is 250 mg every 6 hours for routine skin infections, with 500 mg every 12 hours as an alternative for uncomplicated cases. 3
• The Infectious Diseases Society of America recommends cephalexin 500 mg orally every 6 hours as the preferred oral beta-lactam for methicillin-susceptible Staphylococcus aureus (MSSA) skin and soft tissue infections. 1
• For more severe infections or less susceptible organisms, doses up to 4 grams daily in divided doses may be required. 3

Pediatric Dosing

• The usual pediatric dose is 25-50 mg/kg/day divided into four doses (every 6 hours). 1, 3
• For streptococcal pharyngitis and skin infections in children over 1 year, the total daily dose may be divided and given every 12 hours instead. 3
• For severe infections, the pediatric dosage may be doubled. 3
• Children may require higher doses per kilogram than adults due to greater body water turnover. 4

Treatment Duration

• Treat for exactly 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 2
• For β-hemolytic streptococcal infections specifically, administer cephalexin for at least 10 days. 3
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 2

Renal Dosing Adjustments

• Patients with creatinine clearance less than 30 mL/min require dose reduction proportional to their reduced renal function. 4
• For GFR of 59 mL/min, no dose adjustment is needed—use standard dosing of 500 mg every 6 hours. 2

When Cephalexin Is Appropriate

• Cephalexin is appropriate for nonpurulent cellulitis without drainage, exudate, or MRSA risk factors. 2
• It provides excellent coverage against beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus. 1, 2
• Use cephalexin for impetigo at 250 mg four times daily in adults or 25 mg/kg/day in four divided doses for children. 1

When NOT to Use Cephalexin Alone

• Do NOT use cephalexin monotherapy when MRSA risk factors are present: penetrating trauma, injection drug use, purulent drainage/exudate, known MRSA colonization, or systemic inflammatory response syndrome (SIRS). 2
• In 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
• For severe cellulitis with systemic toxicity, hospitalization with IV vancomycin 15-20 mg/kg every 8-12 hours PLUS piperacillin-tazobactam is mandatory. 2

Penicillin Allergy Considerations

• For patients with penicillin allergy (except immediate hypersensitivity reactions), cephalexin remains an option. 1
• Cross-reactivity between penicillins and cephalosporins is only 2-4%, primarily based on R1 side chain similarity rather than the beta-lactam ring. 1
• Cephalexin shares identical R1 side chains with amoxicillin, so avoid cephalexin in patients with confirmed immediate-type amoxicillin allergy. 1, 5
• For patients with severe immediate-type reactions to any penicillin, use clindamycin 300-450 mg four times daily instead. 2, 5

Cephalosporin Cross-Allergy

• Patients with suspected immediate-type allergy to cephalexin can receive penicillins with dissimilar side chains (avoid amoxicillin/ampicillin). 1
• Cephalosporins with dissimilar side chains can be used in patients with cephalexin allergy, irrespective of severity or timing. 1
• Any carbapenem can be safely used in patients with cephalexin allergy. 1

Special Populations

• Cephalexin is safe in myasthenia gravis—it does not trigger or exacerbate the condition, unlike fluoroquinolones, aminoglycosides, or macrolides. 6
• For diabetic foot infections, cephalexin may be used for mild infections, but moderate-to-severe cases require broader coverage with amoxicillin-clavulanate or fluoroquinolones. 2

Critical Pitfalls to Avoid

• Do NOT reflexively extend treatment to 10-14 days based on residual erythema alone—some inflammation persists after bacterial eradication. 2
• Do NOT add MRSA coverage routinely for typical cellulitis—beta-lactam monotherapy succeeds in 96% of cases. 2
• Do NOT use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis—their streptococcal coverage is unreliable. 2
• Assess for abscess with ultrasound if clinically uncertain—purulent collections require incision and drainage, not antibiotics alone. 2

Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote drainage. 2
• Examine interdigital toe spaces for tinea pedis and treat toe web abnormalities to reduce recurrence risk. 2
• Address predisposing conditions including venous insufficiency, lymphedema, and chronic edema. 2