Can Keflex (cephalexin) be used to treat urinary tract infections (UTIs)?

Can Keflex (Cephalexin) Be Used to Treat UTIs?

Yes, cephalexin is FDA-approved and effective for treating urinary tract infections caused by susceptible organisms including E. coli, Proteus mirabilis, and Klebsiella pneumoniae, though current guidelines recommend it as an alternative rather than first-line agent for uncomplicated UTIs. 1

FDA-Approved Indications

Cephalexin is specifically indicated for genitourinary tract infections, including acute prostatitis, caused by susceptible strains of E. coli, Proteus mirabilis, and Klebsiella pneumoniae. 1 Culture and susceptibility testing should be initiated prior to and during therapy to confirm appropriate coverage. 1

Clinical Context and Guideline Positioning

For Uncomplicated Cystitis

• Cephalosporins (including cephalexin) are listed as alternative agents in the 2024 European Association of Urology guidelines, recommended when local E. coli resistance is <20%. 2
• The recommended dosing is cephalexin 500 mg twice daily for 3 days for uncomplicated cystitis in women. 2
• First-line agents remain fosfomycin, nitrofurantoin, and pivmecillinam. 2

For Complicated UTIs

• Second-generation cephalosporins plus an aminoglycoside receive a strong recommendation for complicated UTIs with systemic symptoms. 2
• Treatment duration should be 7-14 days (14 days for men when prostatitis cannot be excluded). 2

Dosing Strategies: Twice Daily vs Four Times Daily

Recent evidence strongly supports twice-daily dosing (500 mg BID) as equally effective as four-times-daily dosing (500 mg QID) for UTIs:

• A 2023 multicenter study of 261 patients showed no difference in treatment failure between BID (12.7%) and QID (17%) dosing regimens (P = 0.343). 3
• A 2025 emergency department study of 214 patients confirmed no significant difference in treatment failure rates: 18.7% for BID vs 15.0% for QID (P = 0.465). 4
• Twice-daily dosing improves patient adherence while maintaining equivalent efficacy. 3, 4

Clinical Efficacy Data

Overall Success Rates

• A 2023 single-center retrospective review of 264 patients treated with cephalexin for uncomplicated UTIs showed 81.1% clinical success at 30 days. 5
• Only 10.6% required antibiotic change based on culture results, and 6.8% returned for nonresolving symptoms. 5

Patient-Specific Considerations

Age matters significantly:

• Patients <25 years: 87% cure rate with single-dose therapy 6
• Patients >40 years: 46% cure rate with single-dose therapy (P <0.001) 6

Antibody-coated bacteria (ACB) test results predict outcomes:

• ACB-negative infections: 71% cure rate 6
• ACB-positive infections: 19% cure rate (P = 0.003) 6

Comparison with Other Cephalosporins

Cefdinir, despite being frequently prescribed, has markedly lower urine penetration than cephalexin. 7 A 2024 comparative study showed numerically higher treatment failure at 14 days with cefdinir (20.7%) versus cephalexin (11.8%), though not statistically significant (P = 0.053). 7

Practical Prescribing Algorithm

For uncomplicated UTIs in women:

1. Consider cephalexin 500 mg twice daily for 3-5 days if local E. coli resistance to first-line agents is >20% or patient has contraindications to first-line agents 2, 5
2. Obtain urine culture before initiating therapy 2
3. Adjust based on susceptibility results 1

For complicated UTIs or pyelonephritis:

1. Use second-generation cephalosporin plus aminoglycoside for systemic symptoms 2
2. Treat for 7-14 days depending on clinical response and gender 2
3. Ensure underlying urological abnormalities are managed 2

For men with UTIs:

1. Treat for minimum 7 days (consider 14 days if prostatitis cannot be excluded) 2
2. Obtain culture and susceptibility testing in all cases 2

Important Caveats

• Do not use cephalexin for febrile UTIs in infants and young children as it does not achieve therapeutic bloodstream concentrations despite adequate urinary levels. 2
• Cephalexin is not appropriate for multidrug-resistant organisms including carbapenem-resistant Enterobacteriaceae (CRE), which require specialized agents like ceftazidime-avibactam or meropenem-vaborbactam. 2
• Local antibiogram data should guide empiric selection, as geographic resistance patterns vary substantially. 5