Is Keflex (cephalexin) effective for treating a urinary tract infection (UTI)?

Is Keflex (Cephalexin) Effective for UTI Treatment?

Cephalexin is an acceptable but not preferred option for uncomplicated UTIs, reserved for situations when first-line agents (nitrofurantoin, fosfomycin, trimethoprim-sulfamethoxazole) cannot be used, and it should be dosed at 500 mg twice daily for 5-7 days. 1

First-Line vs. Alternative Status

Current guidelines consistently classify cephalexin and other β-lactams as alternative rather than first-line agents for uncomplicated cystitis 1. The 2024 European Association of Urology guidelines do not list cephalexin among recommended first-line options for uncomplicated cystitis, instead prioritizing fosfomycin, nitrofurantoin, and pivmecillinam 1. The 2024 WHO guidelines similarly recommend amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, or nitrofurantoin as preferred choices for lower UTIs 1.

Why Cephalexin is Not First-Line:

• Inferior efficacy: β-lactams generally demonstrate lower cure rates and more adverse effects compared to other UTI antimicrobials 1
• Less well-studied: Cephalexin specifically is "less well studied" than other β-lactam options for uncomplicated cystitis 1
• Broader ecological impact: Greater propensity for collateral damage (disruption of normal flora and resistance promotion) compared to nitrofurantoin or fosfomycin 1

When Cephalexin IS Appropriate

Cephalexin remains a reasonable choice when:

• Other recommended first-line agents cannot be used due to allergies, contraindications, or intolerance 1
• Local resistance patterns favor its use (E. coli resistance <20%) 1
• The pathogen is confirmed susceptible to cefazolin on culture 2, 3

The FDA label confirms cephalexin is indicated for genitourinary tract infections caused by E. coli, Proteus mirabilis, and Klebsiella pneumoniae 4.

Optimal Dosing Strategy

The most important recent finding: 500 mg twice daily is as effective as 500 mg four times daily 2, 3.

• A 2023 multicenter study of 261 patients showed no difference in treatment failure between twice-daily (12.7%) versus four-times-daily dosing (17%, P=0.343) 2
• A 2025 emergency department study of 214 patients confirmed similar findings: 18.7% vs 15.0% failure rates (P=0.465) 3
• Twice-daily dosing improves adherence while maintaining equivalent efficacy 2

Recommended Regimen:

• Dose: 500 mg twice daily (not four times daily)
• Duration: 5-7 days for uncomplicated cystitis 1, 2
• Duration: 7 days for men (to cover possible prostatitis) 1

Clinical Efficacy Data

Cephalexin demonstrates moderate effectiveness for UTIs:

• Single-dose therapy (3g): 67% cure rate overall, but 87% in women <25 years vs only 46% in women >40 years 5
• Standard multi-day therapy: Achieves high urinary concentrations (1000-5000 mcg/mL) with >90% urinary excretion 4
• Active against: E. coli (most common pathogen at 85.4%), Proteus mirabilis, Klebsiella pneumoniae 4, 2
• Not active against: Pseudomonas, Enterococcus, methicillin-resistant Staphylococcus, most Enterobacter species 4

Critical Resistance Considerations

A major limitation: The 2024 WHO GLASS data showed a median of 75% (range 45-100%) of E. coli urinary isolates were resistant to amoxicillin across 22 countries 1. While this specifically addresses amoxicillin, it highlights the importance of knowing local resistance patterns before empirically prescribing any β-lactam, including cephalexin 1.

Type of UTI Matters

Uncomplicated Cystitis:

• Use only when first-line agents unavailable 1
• 500 mg twice daily for 5-7 days 2

Pyelonephritis:

• Oral cephalosporins (cefpodoxime 200 mg twice daily for 10 days or ceftibuten 400 mg daily for 10 days) are listed as alternatives when fluoroquinolones cannot be used 1
• Cephalexin is NOT specifically recommended for pyelonephritis in major guidelines 1

Complicated UTIs:

• Second-generation cephalosporins (not cephalexin, which is first-generation) plus aminoglycosides are recommended for systemic symptoms 1
• Third-generation cephalosporins preferred for severe complicated UTIs 1

Common Pitfalls to Avoid

1. Don't use four-times-daily dosing: Twice daily is equally effective and improves adherence 2, 3
2. Don't use for febrile UTIs/pyelonephritis in children: Insufficient serum concentrations; use agents that achieve therapeutic blood levels 1
3. Don't assume susceptibility: Always obtain culture and tailor therapy, especially given rising resistance rates 1
4. Don't use empirically in high-resistance areas: Check if local E. coli resistance to cephalosporins exceeds 20% 1