Keflex Dosing for Uncomplicated UTI
For uncomplicated cystitis in adults, cephalexin 500 mg every 12 hours for 7-14 days is the recommended dosing regimen, though it should be considered an alternative rather than first-line therapy. 1
Standard Dosing Regimen
The FDA-approved dosing for uncomplicated cystitis in patients over 15 years of age is 500 mg every 12 hours, with therapy continued for 7 to 14 days 1. Recent evidence supports that this twice-daily dosing is as effective as the traditional four-times-daily regimen (500 mg QID), with no difference in treatment failure rates (12.7% vs 17%, P = 0.343) 2.
Important Clinical Context
Position in Treatment Algorithm
Cephalexin is classified as an alternative agent, not first-line therapy, for uncomplicated UTIs 3. Current guidelines recommend:
- First-line options: Fosfomycin 3g single dose, nitrofurantoin 100 mg twice daily for 5 days, or pivmecillinam 400 mg three times daily for 3-5 days 3
- Alternative agents: Cephalosporins (including cephalexin) should only be used when local E. coli resistance is <20% 3
When to Use Cephalexin
Consider cephalexin when:
- First-line agents cannot be used due to allergy, intolerance, or unavailability 3
- Local susceptibility data confirm the pathogen is susceptible 1
- Patient-specific factors preclude use of fluoroquinolones or other first-line agents 3
Pharmacologic Rationale
Cephalexin achieves excellent urinary concentrations of 500-1000 mcg/mL following 250-500 mg oral doses, far exceeding the minimum inhibitory concentration for common uropathogens 4. The drug is 70-100% excreted unchanged in urine within 6-8 hours 4, making it theoretically suitable for UTI treatment despite its classification as an alternative agent.
Critical Caveats
Do not use cephalexin for febrile UTIs or pyelonephritis 3. Agents that achieve only urinary concentrations without adequate tissue/serum levels (like nitrofurantoin and cephalexin in standard doses) are insufficient for upper tract infections where parenchymal penetration is required 3.
Adjust dosing in renal impairment: Patients with creatinine clearance <30 mL/min require dose reduction proportional to their reduced renal function 4.
β-lactams have inferior efficacy compared to fluoroquinolones and trimethoprim-sulfamethoxazole for UTI treatment, with higher rates of treatment failure 3. This explains their relegation to alternative status despite good urinary penetration.