Is Keflex (cephalexin) effective against Escherichia coli (E. coli) infections?

Cephalexin Coverage of E. coli

Cephalexin (Keflex) is effective against susceptible strains of E. coli, particularly for uncomplicated urinary tract infections, but should NOT be used for ESBL-producing E. coli or serious systemic infections. 1, 2

FDA-Approved Indications

The FDA explicitly lists E. coli as a susceptible organism for cephalexin in genitourinary tract infections, including acute prostatitis. 2 The drug demonstrates bactericidal activity through inhibition of bacterial cell wall synthesis and achieves high urinary concentrations (1000-5000 mcg/mL following standard doses), making it particularly suitable for urinary tract infections. 2

Clinical Effectiveness Against E. coli

• For uncomplicated UTIs: Cephalexin 500 mg orally every 6-12 hours is appropriate empiric therapy when local E. coli resistance rates are <20%. 1
• Microbiological activity: In vitro studies confirm cephalexin is active against most E. coli strains, with research showing it maintains effectiveness even in patients with recurrent bacteriuria when used prophylactically at 250 mg nightly. 3
• Clinical outcomes: Historical data demonstrates over 90% of patients remained infection-free during 6-month prophylactic therapy, with minimal resistance development at low doses. 3

Critical Contraindications and Limitations

Absolute contraindications for cephalexin use:

• ESBL-producing E. coli: Cephalexin is completely ineffective against extended-spectrum beta-lactamase-producing organisms and must never be used for suspected or confirmed ESBL infections. 1
• Serious systemic infections: Cephalexin should NOT be used as monotherapy for bacteremia, endocarditis, or other severe systemic E. coli infections requiring parenteral therapy. 1
• Severe infections requiring broad coverage: Third-generation cephalosporins or carbapenems are preferred over cephalexin for life-threatening infections. 1

Resistance Considerations

Local resistance patterns are critical—geographic variability in E. coli susceptibility to cephalexin is substantial. 1 Culture and susceptibility testing should be initiated prior to and during therapy, with MIC interpretation following standardized criteria (susceptible ≤8 mcg/mL, resistant ≥32 mcg/mL). 2

Comparative Potency

Among cephalosporins tested against E. coli, the relative potency in decreasing order is: cefazolin > cephaloridine > cephalexin > cephalothin. 4 This positions cephalexin as less potent than parenteral first-generation cephalosporins but still clinically effective for susceptible strains. 4

Practical Algorithm for Use

1. Confirm infection type: Uncomplicated UTI or simple skin/soft tissue infection → consider cephalexin
2. Assess severity: Mild-to-moderate infection without systemic toxicity → cephalexin appropriate; severe/systemic infection → use parenteral broader-spectrum agents 1
3. Check local resistance data: If E. coli resistance to cephalexin <20% locally → proceed; if ≥20% → choose alternative 1
4. Rule out ESBL risk factors: Recent hospitalization, healthcare exposure, prior antibiotic use, or known ESBL carriage → avoid cephalexin entirely 1
5. Obtain cultures: Always send urine culture before initiating therapy to guide definitive treatment 2