Cephalexin Dosing
For adults with normal renal function, cephalexin should be dosed at 500 mg four times daily (every 6 hours) for most infections, though twice-daily dosing of 500 mg every 12 hours is acceptable for uncomplicated cystitis, streptococcal pharyngitis, and mild skin infections. 1, 2
Adult Dosing Regimens
Standard Dosing for Most Infections
- 500 mg four times daily (every 6 hours) is the recommended dose for skin and soft tissue infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) 1, 3, 2
- The total daily dose ranges from 1-4 grams divided throughout the day 2
- For more severe infections or less susceptible organisms, higher doses may be needed, but if >4 grams daily is required, parenteral cephalosporins should be considered 2
Reduced Frequency Dosing Options
- 500 mg every 12 hours (twice daily) is FDA-approved for:
- Recent evidence supports twice-daily dosing (500 mg BID) as equally effective as four-times-daily dosing for uncomplicated urinary tract infections, with no difference in treatment failure rates (12.7% vs 17%, P=0.343) 4, 5
- Twice-daily dosing may improve patient adherence without compromising effectiveness 4, 5
Lower Dose Options
Pediatric Dosing
Standard Pediatric Dosing
- 25-50 mg/kg/day divided into 4 doses for mild to moderate infections 1, 2
- 75-100 mg/kg/day divided into 3-4 doses for MSSA infections 1, 3
- For streptococcal pharyngitis and skin infections in children >1 year, the total daily dose may be divided and given every 12 hours 2
Otitis Media
- 75-100 mg/kg/day in 4 divided doses is required for adequate treatment 2
β-Hemolytic Streptococcal Infections
- Continue therapeutic dosing for at least 10 days 2
Infection-Specific Considerations
Skin and Soft Tissue Infections
- Adults: 500 mg four times daily 1, 3
- Children with mild infections: 25-50 mg/kg/day in 4 divided doses 1
- Children with MSSA: 75-100 mg/kg/day in 3-4 divided doses 1
Mastitis
- 500 mg orally every 6 hours (four times daily) for lactating women 1
- Cephalexin achieves therapeutic levels in breast milk and is safe for nursing infants 1
- Switch to trimethoprim-sulfamethoxazole or clindamycin if MRSA is suspected 1
Respiratory Tract Infections
- Adults: 500 mg four times daily 1
- Children: 25-50 mg/kg/day in 4 divided doses 1
- Important caveat: Cephalexin has poor activity against Haemophilus influenzae and Moraxella catarrhalis, making it inappropriate for acute bacterial sinusitis and many respiratory infections 1, 3
Animal Bites
- 500 mg 3-4 times per day orally 3
- Critical limitation: First-generation cephalosporins have poor activity against Pasteurella multocida, commonly found in animal bites, so alternative agents should be strongly considered 3
Duration of Therapy
- Typically 7-10 days for most infections, depending on clinical response 1
- Cystitis: 7-14 days 2
- β-hemolytic streptococcal infections: minimum 10 days 2
Renal Dosing Adjustments
- Patients with creatinine clearance <30 mL/min require dose reduction proportional to reduced renal function 6
- Even with impaired renal function, urinary concentrations remain adequate for treating most UTIs caused by E. coli, Klebsiella, and Proteus mirabilis 7
- In anephric patients, single doses of 250-500 mg result in high, prolonged serum concentrations 7
- Hemodialysis for 6 hours reduces serum cephalexin concentration by 58% 7
Critical Limitations and Contraindications
Spectrum Gaps
- Completely ineffective against MRSA 1, 3
- Poor activity against H. influenzae and M. catarrhalis 1
- Completely ineffective against Pseudomonas aeruginosa 1
- Poor activity against Pasteurella multocida 3
- Not suitable for infective endocarditis prophylaxis due to 96% resistance rates among viridans group streptococci 1