Is Keflex (cephalexin) effective against E coli urinary tract infections (UTIs)?

Effectiveness of Keflex (Cephalexin) Against E. coli UTIs

Keflex (cephalexin) is effective against most strains of E. coli in urinary tract infections, as it is specifically FDA-approved for genitourinary tract infections caused by E. coli and achieves high urinary concentrations that are adequate for treating most E. coli UTIs. 1

Mechanism and Pharmacology

Cephalexin is a first-generation cephalosporin that works by inhibiting bacterial cell wall synthesis. When administered orally:

• It is rapidly absorbed from the gastrointestinal tract regardless of food intake
• Peak serum levels occur approximately 1 hour after administration
• Over 90% is excreted unchanged in the urine within 8 hours
• Achieves very high urinary concentrations (1000-5000 mcg/mL depending on dose) 1
• These high urinary concentrations exceed the MIC needed for most urinary E. coli strains 2

Efficacy Against E. coli

The FDA label specifically lists E. coli as a susceptible organism for genitourinary tract infections treated with cephalexin 1. Recent studies support its continued effectiveness:

• A 2023 study found that cephalexin was effective for uncomplicated UTIs with an 81.1% clinical success rate, with E. coli being the most commonly isolated pathogen (85.4% of cases) 3, 4
• Even in patients with impaired renal function, urinary concentrations remain adequate for treating most E. coli UTIs 2

Dosing Recommendations

For uncomplicated UTIs caused by E. coli:

• 500 mg twice daily for 5-7 days is as effective as 500 mg four times daily 3
• The twice-daily regimen may improve patient adherence while maintaining efficacy 3
• For prophylaxis in recurrent UTIs, 125-250 mg daily has shown effectiveness 5, 6

Important Considerations and Limitations

1. Resistance patterns: While cephalexin is effective against most E. coli strains, local resistance patterns should be considered:

   • It has no activity against Pseudomonas or Acinetobacter species 1
   • Some strains of Enterobacter, Morganella morganii, and Proteus vulgaris are resistant 1

2. Position in treatment guidelines:

   • β-lactams (including cephalexin) are generally considered alternative rather than first-line agents for uncomplicated UTIs 3, 4
   • First-line options typically include nitrofurantoin, trimethoprim-sulfamethoxazole, and fosfomycin 5

3. Special populations:

   • For pregnant patients, cephalexin is considered safe and is among the recommended options 5
   • In elderly patients, dose adjustment may be needed based on renal function 5
   • Avoid in patients with severe penicillin allergy (approximately 10% cross-reactivity) 5

For Multidrug-Resistant E. coli

For carbapenem-resistant E. coli (CRE) UTIs, cephalexin is not effective, and the following options are recommended:

• Ceftazidime-avibactam, meropenem-vaborbactam, or imipenem-cilastatin-relebactam for complicated UTIs 7
• Single-dose aminoglycoside for simple cystitis due to CRE 7

Conclusion

Keflex (cephalexin) remains an effective option for most E. coli UTIs, particularly when first-line agents cannot be used due to allergies, resistance patterns, or other contraindications. Its high urinary concentrations and specific FDA approval for E. coli genitourinary infections support its use, with twice-daily dosing providing good efficacy and potentially better adherence than more frequent dosing regimens.