What is the appropriate dosing regimen, duration, and renal adjustment for Cephalexin 500 mg in an adult without renal impairment for uncomplicated skin and soft‑tissue infection?

Cephalexin 500mg Dosing for Uncomplicated Skin and Soft‑Tissue Infection in Adults

For an adult without renal impairment with uncomplicated skin and soft‑tissue infection, prescribe cephalexin 500 mg orally every 6 hours (four times daily) for exactly 5 days if clinical improvement occurs; extend only if warmth, tenderness, or erythema have not improved within this timeframe. 1, 2, 3, 4

Standard Dosing Regimen

• Cephalexin 500 mg orally every 6 hours (QID) is the recommended dose for methicillin‑susceptible Staphylococcus aureus (MSSA) and streptococcal skin infections in adults with normal renal function. 1, 3, 5, 4

• The FDA‑approved adult dosage ranges from 1 to 4 grams daily in divided doses, with 500 mg every 6 hours falling within this therapeutic window for skin and soft‑tissue infections. 4

• Four‑times‑daily dosing is necessary because cephalexin's short half‑life (approximately 1 hour) requires administration every 6 hours to maintain adequate tissue concentrations; three‑times‑daily dosing is suboptimal and may lead to treatment failure. 3, 6

Treatment Duration

• Treat for exactly 5 days if clinical improvement is evident (resolution of warmth and tenderness, improving erythema, absence of fever); this duration is supported by high‑quality randomized controlled trial evidence showing no difference in outcomes compared with 10‑day courses for uncomplicated cellulitis. 2, 3

• Extend treatment beyond 5 days only if symptoms have not improved within this initial period; traditional 7–14‑day regimens are no longer necessary for uncomplicated cases. 2, 3

• Reassess the patient within 24–48 hours to verify clinical response, as treatment failure rates of approximately 21% have been reported with some oral regimens if no improvement is seen. 2

When Cephalexin Is Appropriate

• Beta‑lactam monotherapy (cephalexin) achieves approximately 96% clinical success in typical non‑purulent cellulitis because the primary pathogens are beta‑hemolytic streptococci (especially Streptococcus pyogenes) and methicillin‑sensitive Staphylococcus aureus. 1, 2, 3

• Cephalexin is the oral agent of choice for penicillin‑allergic patients with non‑immediate hypersensitivity reactions (e.g., delayed rash), as cross‑reactivity between penicillins and cephalosporins is only 2–4%. 1, 2, 3

• Use cephalexin for uncomplicated, non‑purulent cellulitis without drainage, exudate, or systemic signs of infection in patients who can self‑monitor with close follow‑up. 2, 5

When to Avoid Cephalexin and Add MRSA Coverage

Do not use cephalexin alone when any of the following MRSA risk factors are present:

• Penetrating trauma or injection drug use 2, 3
• Purulent drainage or exudate at the infection site 2, 3
• Known MRSA colonization or prior MRSA infection 2, 3
• Systemic inflammatory response syndrome (fever >38°C, tachycardia >90 bpm, tachypnea >24 breaths/min, hypotension, altered mental status) 2, 3
• Failure to respond to beta‑lactam therapy after 48–72 hours 2, 3

When MRSA coverage is required, use:

• Clindamycin 300–450 mg orally every 6 hours as single‑agent therapy (covers both streptococci and MRSA), provided local MRSA clindamycin resistance is <10%. 2, 3
• Trimethoprim‑sulfamethoxazole 1–2 double‑strength tablets twice daily PLUS cephalexin 500 mg every 6 hours (combination required because TMP‑SMX lacks reliable streptococcal coverage). 2, 3
• Doxycycline 100 mg orally twice daily PLUS cephalexin 500 mg every 6 hours (combination required because doxycycline lacks reliable streptococcal coverage). 2, 3

Renal Dose Adjustment

• No dose adjustment is required for adults with creatinine clearance ≥30 mL/min (including your patient with normal renal function). 4, 6

• For creatinine clearance <30 mL/min, reduce the cephalexin dose proportionally to the reduced renal function, as 70–100% of the dose is excreted unchanged in the urine within 6–8 hours. 4, 6

Critical Pitfalls to Avoid

• Do not add MRSA coverage reflexively for typical non‑purulent cellulitis without specific risk factors, as MRSA is an uncommon cause even in high‑prevalence settings; this represents overtreatment and promotes antimicrobial resistance. 2, 3

• Do not use doxycycline or trimethoprim‑sulfamethoxazole as monotherapy for typical cellulitis, as they lack reliable activity against beta‑hemolytic streptococci, the predominant pathogens. 2, 3

• Do not automatically extend therapy to 7–10 days based on residual erythema alone, as inflammation may persist for 1–2 weeks after bacterial eradication; extend only if warmth, tenderness, or expanding borders are present. 2, 3

• Do not use cephalexin for suspected necrotizing infections, which require broad‑spectrum IV antibiotics (vancomycin plus piperacillin‑tazobactam) and urgent surgical debridement. 2, 5

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, which hastens clinical improvement. 2, 3

• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration, and treat if present to eradicate colonization and reduce recurrent infection risk. 2, 3

• Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, obesity, and eczema to prevent recurrence. 2, 3