Is cephalexin (Cephalexin) effective against Escherichia coli (E. coli)?

Cephalexin Coverage of E. coli

Yes, cephalexin is active against most strains of E. coli and is FDA-approved for treating genitourinary tract infections caused by susceptible E. coli strains. 1

Microbiological Activity

Cephalexin demonstrates reliable in vitro activity against E. coli:

• The FDA label explicitly lists E. coli as a susceptible organism for which cephalexin is indicated, particularly for genitourinary tract infections 1
• Historical susceptibility data shows 80-85% of E. coli strains are inhibited by 12.5 mcg/mL, with 90-96% inhibited at 25 mcg/mL 2
• Urinary concentrations are exceptionally high, reaching approximately 1000-5000 mcg/mL after standard doses, far exceeding the MIC needed for most E. coli strains 1, 2

Clinical Effectiveness

The drug achieves adequate concentrations for E. coli infections:

• Peak serum levels of 7.7-12.3 mcg/mL after 250-500 mg doses are sufficient to inhibit approximately 85% of E. coli strains 2
• Over 90% of administered cephalexin is excreted unchanged in urine within 6-8 hours, making it particularly effective for urinary tract infections caused by E. coli 1, 2
• Long-term prophylactic use (250 mg nightly) maintained effectiveness against E. coli without developing resistance in a 6-month study of recurrent UTI patients 3

Important Caveats and Resistance Concerns

First-generation cephalosporins like cephalexin are NOT effective against all E. coli strains:

• Cephalexin is ineffective against ESBL-producing E. coli and should never be used for suspected or confirmed extended-spectrum beta-lactamase infections 4
• Local resistance patterns must be considered, as geographic variability in E. coli susceptibility to cephalexin is substantial 4
• Cephalothin susceptibility testing may overestimate cephalexin effectiveness, and laboratories should ideally test cephalexin directly rather than using cephalothin as a surrogate 5
• Resistance mechanisms include OmpF porin downregulation, which can occur without beta-lactamase production and may not be detected by standard susceptibility testing 6

Clinical Application Algorithm

For uncomplicated UTIs with suspected E. coli:

• Cephalexin 500 mg orally every 6-12 hours is appropriate for empiric therapy if local resistance rates are <20% 4, 1
• Duration should be 7-14 days for febrile UTIs 4

For complicated infections or sepsis:

• Cephalexin should NOT be used as monotherapy for serious systemic E. coli infections requiring parenteral therapy 4
• Third-generation cephalosporins or carbapenems are preferred for severe infections 4

Contraindications to cephalexin use:

• Known ESBL-producing organisms 4
• Severe systemic infections requiring broad gram-negative coverage 4
• History of anaphylaxis to beta-lactam antibiotics 7