Keflex Dosing for Uncomplicated UTI
For uncomplicated UTI (cystitis), prescribe cephalexin 500 mg every 12 hours (twice daily) for 7-14 days, though cephalexin should be reserved as an alternative agent when first-line options cannot be used. 1, 2
Dosing Regimen
- The FDA-approved dose for uncomplicated cystitis is 500 mg every 12 hours 2
- Treatment duration should be 7-14 days for uncomplicated cystitis 2
- The twice-daily (BID) dosing is as effective as four-times-daily (QID) dosing and improves adherence 3, 4
Clinical Evidence Supporting Twice-Daily Dosing
- A 2023 multicenter study demonstrated no difference in treatment failure between 500 mg BID (12.7% failure) versus 500 mg QID (17% failure) regimens 3
- Another 2025 study confirmed similar treatment failure rates of 18.7% for BID versus 15.0% for QID dosing, with no statistically significant difference 4
- Twice-daily dosing offers the advantage of improved patient adherence without compromising effectiveness 3, 4
Position in Treatment Algorithm
- Cephalexin is considered an alternative rather than first-line agent for uncomplicated UTI by the Infectious Diseases Society of America 1
- β-lactams like cephalexin have inferior efficacy and more adverse effects compared to other UTI antimicrobials 1
- Reserve cephalexin for situations when first-line agents (nitrofurantoin, trimethoprim-sulfamethoxazole, or fosfomycin) cannot be used due to allergy, resistance patterns, or contraindications 1
Pharmacologic Rationale
- Cephalexin achieves urinary concentrations of 500-1000 mcg/mL following 250-500 mg oral doses, which far exceeds the minimum inhibitory concentration for typical uropathogens 5
- The drug is 70-100% excreted unchanged in urine within 6-8 hours, providing excellent urinary penetration 5
- Most UTI isolates in recent studies were Escherichia coli (85.4%), which typically shows good susceptibility to cephalosporins 3
Important Caveats
- Adjust dosing in renal impairment: Patients with creatinine clearance <30 mL/min require dose reduction proportional to reduced kidney function 5
- For catheter-associated UTI, treatment duration extends to 7-14 days depending on symptom resolution, but this represents a different clinical entity than uncomplicated UTI 6
- Clinical success rates of approximately 81% have been demonstrated with twice-daily cephalexin for uncomplicated UTI 7