Treatment of Recurrent UTIs with Keflex (Cephalexin)
Cephalexin should not be used as first-line therapy for recurrent UTIs, but may be considered as an alternative agent when first-line options (nitrofurantoin, trimethoprim-sulfamethoxazole, or fosfomycin) cannot be used, with dosing of 500 mg twice daily for 5-7 days for acute episodes. 1, 2
First-Line Treatment Approach for Acute Episodes
When treating acute cystitis episodes in patients with recurrent UTIs:
Nitrofurantoin (100 mg twice daily for 5 days), fosfomycin trometamol (3 g single dose), or trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) are the recommended first-line agents due to lower collateral damage and resistance concerns 1
Cephalexin is classified as an alternative or second-line agent because β-lactams generally have inferior efficacy and more adverse effects compared to first-line UTI antimicrobials 1
If cephalexin must be used, prescribe 500 mg twice daily for 5-7 days rather than the traditional four-times-daily dosing, as twice-daily dosing demonstrates equivalent efficacy with improved adherence 3, 4
Critical Diagnostic Requirements
Always obtain urine culture before treating recurrent UTIs to confirm diagnosis and guide antimicrobial selection 1, 2
Verify local resistance patterns for E. coli to cephalexin before empirical use, as geographic variability in resistance is substantial 1
Do not treat asymptomatic bacteriuria in non-pregnant women with recurrent UTIs, as this does not reduce recurrence and promotes resistance 1
Prevention Strategy Algorithm
Step 1: Non-Antimicrobial Prophylaxis (Strongly Recommended First)
- Vaginal estrogen replacement for postmenopausal women 2
- Methenamine hippurate 2
- Immunoactive prophylaxis 2
- Increased fluid intake 1, 2
Step 2: Antimicrobial Prophylaxis (Only After Non-Antimicrobial Failure)
If non-antimicrobial measures fail, consider continuous prophylaxis with nitrofurantoin, trimethoprim-sulfamethoxazole, or fosfomycin 1, 2
Cephalexin is NOT recommended for prophylaxis due to resistance concerns and availability of superior alternatives 2
Duration of prophylaxis typically ranges from 6-12 months with periodic reassessment 1
Dosing Adjustments and Special Populations
For creatinine clearance <30 mL/min, extend the dosing interval as cephalexin is renally excreted and accumulates in renal impairment 2, 5
In elderly patients, cephalexin achieves adequate urinary concentrations even with impaired renal function for treating most E. coli, Klebsiella, and Proteus mirabilis infections 5, 6
Common Pitfalls to Avoid
Do not use cephalexin empirically if local E. coli resistance exceeds 20% without culture confirmation 1
Do not prescribe single-dose cephalexin therapy, as this increases bacteriological persistence compared to 3-7 day courses 1
Do not perform routine post-treatment cultures in asymptomatic patients 1
Do not perform extensive workup (cystoscopy, full abdominal ultrasound) in women <40 years with recurrent UTI and no risk factors 1
When Treatment Fails
If symptoms persist or recur within 2 weeks, obtain urine culture and assume the organism is not susceptible to the original agent 1
Retreat with a 7-day course using a different antimicrobial class based on culture results 1
For culture-resistant organisms requiring parenteral therapy, treat for as short a course as reasonable, generally no longer than 7 days 1
Evidence Quality Note
The recommendation against cephalexin as first-line therapy is based on high-quality 2024 European Association of Urology guidelines and 2019 AUA/CUA/SUFU guidelines, which emphasize antimicrobial stewardship and collateral damage prevention 1, 2. While cephalexin remains FDA-approved for genitourinary tract infections caused by E. coli, Proteus mirabilis, and Klebsiella pneumoniae 7, contemporary guidelines prioritize agents with better resistance profiles and less ecological impact.