Will Keflex Treat an E. coli UTI Sensitive to Cefazolin?
Yes, Keflex (cephalexin) will effectively treat an E. coli UTI that is sensitive to cefazolin, as cefazolin susceptibility reliably predicts susceptibility to oral first-generation cephalosporins including cephalexin. 1, 2
Rationale for Using Cephalexin Based on Cefazolin Susceptibility
Cefazolin serves as the appropriate surrogate marker for determining susceptibility to first-generation oral cephalosporins, including cephalexin. 2 Research demonstrates 100% agreement between cefazolin and cephalexin susceptibility testing methods for common uropathogens, and cefazolin can reliably predict susceptibility to other oral first-generation cephalosporins like cefadroxil. 2
The FDA-approved indication for cephalexin explicitly includes genitourinary tract infections caused by E. coli, and the label emphasizes that culture and susceptibility tests should guide therapy. 1 When your isolate shows cefazolin sensitivity, this directly translates to cephalexin efficacy.
Clinical Evidence Supporting Effectiveness
Recent high-quality studies confirm excellent clinical outcomes with cephalexin for E. coli UTIs:
- Treatment failure rates are low (12.7-18.7%) when E. coli isolates are cefazolin-susceptible, with no significant difference between dosing regimens. 3, 4
- Cefazolin demonstrates 92.5% susceptibility against E. coli, K. pneumoniae, and P. mirabilis in urinary isolates, making first-generation cephalosporins highly effective for most community-acquired UTIs. 5
- E. coli remains the predominant uropathogen (85-92%) in UTI studies, and cephalexin shows consistent efficacy when susceptibility is confirmed. 3, 6
Recommended Dosing Strategy
For uncomplicated UTIs, prescribe cephalexin 500 mg twice daily for 5-7 days rather than the traditional four-times-daily dosing. 3, 4 This recommendation is based on:
- Twice-daily dosing shows equivalent treatment failure rates compared to four-times-daily dosing (no statistically significant difference). 3, 4
- Improved patient adherence with twice-daily regimens without compromising effectiveness. 3, 4
- Reduced cost and increased convenience for patients. 4
For complicated UTIs or when prostatitis cannot be excluded in men, consider extending treatment to 14 days. 7
Antimicrobial Stewardship Considerations
Choosing cephalexin over broader-spectrum agents like ceftriaxone significantly reduces the risk of Clostridioides difficile infection. 5 Specifically:
- Ceftriaxone more than doubles the risk of hospital-onset C. difficile infection compared to cefazolin (adjusted OR 2.44,95% CI 1.25-4.76). 5
- First-generation cephalosporins carry no statistical risk for C. difficile, while third-generation cephalosporins pose the highest risk among all antibiotic classes. 5
Current guidelines classify β-lactams as alternative rather than first-line agents for uncomplicated UTI, recommending them when other agents (trimethoprim-sulfamethoxazole, nitrofurantoin, fosfomycin) cannot be used. 7 However, when you have confirmed cefazolin susceptibility, cephalexin becomes an excellent targeted therapy choice. 1, 2
Important Caveats
- β-lactams generally have slightly inferior efficacy compared to fluoroquinolones or trimethoprim-sulfamethoxazole, but this difference is clinically acceptable when susceptibility is confirmed. 7
- Avoid empiric use of cephalexin without susceptibility data if local E. coli resistance to first-generation cephalosporins exceeds 10-20%. 7
- Do not use cephalexin for febrile UTIs suggesting pyelonephritis or urosepsis unless combined with initial parenteral therapy, as adequate tissue penetration for severe infections requires consideration of broader-spectrum agents. 7
- Amoxicillin and ampicillin should never be used empirically due to very high resistance rates worldwide, even though they are penicillins. 7