Keflex Course for Uncomplicated UTI
For uncomplicated cystitis in adults with normal renal function, prescribe cephalexin 500 mg every 12 hours for 7 to 14 days. 1
Dosing Regimen
- Standard dose: Cephalexin 500 mg orally every 12 hours 1
- Duration: 7 to 14 days for uncomplicated cystitis 1
- Alternative dosing: 250 mg every 6 hours is also FDA-approved, but the twice-daily regimen improves adherence without compromising efficacy 1, 2
Recent evidence demonstrates that twice-daily dosing (500 mg BID) is as effective as four-times-daily dosing (500 mg QID) for uncomplicated UTI, with no difference in treatment failure rates (12.7% vs 17%, p=0.343) 2. The twice-daily regimen offers the practical advantage of improved patient compliance while maintaining therapeutic efficacy.
Important Clinical Context
Cephalexin is NOT a first-line agent for uncomplicated UTI. Current guidelines from the Infectious Diseases Society of America classify β-lactam antibiotics, including cephalexin, as alternative rather than first-line therapy 3. First-line agents include:
When Cephalexin Is Appropriate
Use cephalexin when first-line agents cannot be used due to:
- Documented resistance patterns 3
- Patient allergies to preferred agents 3
- Local resistance rates exceeding thresholds for fluoroquinolones or trimethoprim-sulfamethoxazole 3
Pharmacologic Rationale
Cephalexin achieves urinary concentrations of 500-1000 mcg/mL following 250-500 mg oral doses, far exceeding the minimum inhibitory concentration for common uropathogens 4. It is completely absorbed in the upper intestine and 70-100% is excreted unchanged in urine within 6-8 hours 4. This excellent urinary penetration supports its efficacy despite being a second-line agent 5.
Critical Caveats
Do NOT use cephalexin for pyelonephritis: Oral cephalosporins achieve significantly lower blood concentrations than IV formulations and are not adequately studied for upper tract infections 3. For pyelonephritis, use cefpodoxime 200 mg BID for 10 days or ceftibuten 400 mg daily for 10 days, preferably with an initial IV dose of ceftriaxone 3
Renal dosing required: Patients with creatinine clearance <30 mL/min require dose reduction proportional to renal function 4
Verify susceptibility: Always obtain urine culture before initiating therapy when possible, as cephalexin resistance varies geographically 3
Males and complicated UTI: For men or patients with complicating factors (diabetes, immunosuppression, anatomic abnormalities), consider 7-14 days of therapy, with 14 days preferred when prostatitis cannot be excluded 3
Duration Considerations
While the FDA label states 7-14 days 1, emerging data on short-course therapy for complicated UTI suggests 7 days may be sufficient for most uncomplicated cases 3. However, given cephalexin's status as a second-line agent with less robust efficacy data than fluoroquinolones, err toward 10-14 days for uncomplicated cystitis to ensure adequate treatment and minimize recurrence risk.