Keflex Dosing for Uncomplicated UTI
For uncomplicated cystitis in adults, prescribe cephalexin 500 mg orally every 12 hours for 7-14 days. 1
Standard Dosing Regimen
The FDA-approved dosing for uncomplicated cystitis is 500 mg every 12 hours (twice daily) for patients over 15 years of age, with treatment duration of 7-14 days 1. While the traditional FDA label mentions 250 mg every 6 hours as the "usual adult dose," the specific indication for uncomplicated cystitis explicitly allows for the 500 mg twice-daily regimen 1.
Evidence Supporting Twice-Daily Dosing
Recent high-quality evidence strongly supports twice-daily dosing over the traditional four-times-daily regimen:
A 2023 multicenter retrospective study of 261 female patients demonstrated no difference in treatment failure between cephalexin 500 mg twice daily versus four times daily (12.7% vs 17%, P = 0.343) 2. This study specifically evaluated cefazolin-susceptible organisms causing symptomatic uncomplicated UTI.
A 2025 emergency department study of 214 patients found no statistically significant difference in treatment failure rates between twice-daily and four-times-daily dosing (18.7% vs 15.0%, P = 0.465) 3. For uncomplicated UTIs specifically, failure rates were 14.9% versus 8.1% (P = 0.197) 3.
A 2023 single-center review of 264 patients treated with twice-daily cephalexin showed an 81.1% clinical success rate for empiric treatment of uncomplicated UTIs 4.
Important Clinical Context
β-lactams like cephalexin are considered alternative rather than first-line agents for uncomplicated UTI according to IDSA guidelines 5. The guidelines note that β-lactams generally have inferior efficacy and more adverse effects compared to other UTI antimicrobials 5. However, cephalexin remains appropriate when:
- First-line agents (nitrofurantoin, trimethoprim-sulfamethoxazole, fosfomycin) cannot be used 5
- Local resistance patterns favor cephalosporins 4
- The organism is known to be susceptible 1
Practical Advantages of Twice-Daily Dosing
Twice-daily dosing improves patient adherence without compromising effectiveness 2, 3. Cephalexin achieves urinary concentrations of 500-1000 mcg/mL following 250-500 mg oral doses, far exceeding the minimum inhibitory concentration for typical uropathogens 6. The drug is completely absorbed in the upper intestine and 70-100% is excreted unchanged in urine within 6-8 hours 6.
Dosing Adjustments
Reduce dosage proportionally in patients with creatinine clearance <30 mL/min based on the degree of renal impairment 6.