Keflex Dosing for Skin Infections
Standard Adult Dosing Regimen
For typical adult skin infections, cephalexin should be dosed at 500 mg orally every 6 hours (four times daily) for 5-7 days, with treatment extension only if clinical improvement has not occurred within this timeframe. 1, 2
The FDA-approved dosing for skin and skin structure infections ranges from 250 mg every 6 hours to 500 mg every 12 hours, depending on infection severity 2. However, the IDSA guidelines specifically recommend the 500 mg four times daily regimen as the preferred approach for most skin infections 1.
Dosing Adjustments for Renal Impairment
Patients with impaired renal function require dose modification, as cephalexin is renally cleared with 70-100% of the dose appearing unchanged in urine within 6-8 hours. 3
Specific Renal Dosing Guidelines:
- Creatinine clearance >50 mL/min: No adjustment needed; use standard 500 mg every 6 hours 3
- Creatinine clearance 30-50 mL/min: Reduce frequency to every 8-12 hours while maintaining the 500 mg dose 3
- Creatinine clearance <30 mL/min: Dosage reduction proportional to reduced renal function is required 3
- 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 4
For patients with creatinine clearance around 59 mL/min (mild renal impairment), the standard 500 mg every 6 hours dose typically requires no adjustment, though monitoring for clinical response is prudent. 3
Treatment Duration
The evidence strongly supports 5-day treatment courses for uncomplicated cellulitis when clinical improvement is evident, rather than traditional 7-14 day regimens. 1, 5
The IDSA guidelines explicitly state that treatment should be extended beyond 5 days only if the infection has not improved within this initial period 1, 5. This shorter duration applies specifically to nonpurulent cellulitis without systemic toxicity, MRSA risk factors, or complications 1.
When Cephalexin Is Appropriate vs. When It's Not
Appropriate Use:
- Nonpurulent cellulitis without drainage or exudate 1
- Methicillin-susceptible Staphylococcus aureus (MSSA) and streptococcal infections 1
- Impetigo caused by Staphylococcus and Streptococcus species 1
- Penicillin-allergic patients without immediate hypersensitivity reactions 1
Inappropriate Use - MRSA Coverage Required:
Do not use cephalexin monotherapy when any of these MRSA risk factors are present: 1
- Purulent drainage or exudate
- Penetrating trauma or injection drug use
- History of MRSA colonization or infection
- Failed initial beta-lactam therapy
- Systemic inflammatory response syndrome (SIRS)
For these scenarios, switch to clindamycin 300-450 mg four times daily, or combine trimethoprim-sulfamethoxazole with a beta-lactam 1, 5.
Critical Pitfalls to Avoid
The most common error is adding unnecessary MRSA coverage to typical nonpurulent cellulitis. Beta-lactam monotherapy succeeds in 96% of typical cellulitis cases, even in high MRSA-prevalence settings, because MRSA is an uncommon cause of nonpurulent cellulitis 5.
Never use cephalexin for suspected necrotizing infections, which require broad-spectrum IV antibiotics (vancomycin plus piperacillin-tazobactam) and urgent surgical intervention 1.
Do not reflexively extend treatment to 10-14 days based on residual erythema alone, as some inflammation persists even after bacterial eradication 5. Extend treatment only if warmth, tenderness, and erythema fail to improve after 5 days 5.
Adjunctive Measures That Accelerate Recovery
Elevation of the affected extremity above heart level for at least 30 minutes three times daily promotes gravitational drainage and hastens improvement. 5
Examine and treat interdigital toe spaces for tinea pedis, fissuring, or maceration, as eradicating this colonization reduces recurrent infection risk 5. Address underlying venous insufficiency, lymphedema, and chronic edema as part of routine care 5.