Can cephalexin (a first-generation cephalosporin) be prescribed if cefazolin (a first-generation cephalosporin) is suspected to be ineffective due to resistance in a urinary tract infection (UTI)?

Cephalexin Cannot Be Prescribed Based on Cefazolin Susceptibility

No, you cannot prescribe cephalexin based solely on cefazolin susceptibility results from a urinalysis, as both are first-generation cephalosporins with essentially identical antimicrobial spectra—if the organism is resistant to cefazolin, it will be resistant to cephalexin. 1

Understanding Cross-Resistance Between First-Generation Cephalosporins

• Cefazolin and cephalexin share the same antimicrobial activity against common uropathogens, particularly E. coli and other Enterobacteriaceae 1
• The Clinical and Laboratory Standards Institute (CLSI) and United States Committee on Antimicrobial Susceptibility Testing (USCAST) now recommend cefazolin-cephalexin surrogate testing, meaning cefazolin susceptibility results can predict cephalexin susceptibility—but this works in both directions 1
• If your urinalysis shows cefazolin resistance, this indicates the organism has mechanisms (typically beta-lactamases) that will also render cephalexin ineffective 1

When Cephalexin Is Appropriate for UTI Treatment

Cephalexin should only be prescribed when:

• Susceptibility testing confirms the organism is susceptible to cefazolin (which predicts cephalexin susceptibility) 1
• The infection is caused by non-ESBL-producing Enterobacteriaceae 1
• Local resistance patterns show <20% resistance to first-generation cephalosporins 2
• The patient has uncomplicated cystitis or pyelonephritis without signs of sepsis 2

Effective Cephalexin Dosing When Susceptible

• 500 mg twice daily for 5-7 days is as effective as four-times-daily dosing for uncomplicated UTI and improves adherence 3
• For febrile UTI in children, 50-100 mg/kg per day in 4 doses for 7-14 days is recommended 2
• Cephalexin achieves high urinary concentrations exceeding 1000 mg/L even with standard dosing 4

Alternative Antibiotics When Cefazolin Shows Resistance

If cefazolin susceptibility testing indicates resistance, consider:

• Nitrofurantoin 100 mg twice daily for 5 days (first-line for uncomplicated cystitis) 2
• Fosfomycin 3g single dose (first-line for women with uncomplicated cystitis) 2
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days (if local resistance <20%) 2
• Second or third-generation cephalosporins (cefuroxime, cefpodoxime) if susceptibility confirmed 2

Critical Action Required

• Obtain urine culture with antimicrobial susceptibility testing before selecting an alternative agent 2
• Do not assume susceptibility to any beta-lactam antibiotic when cefazolin resistance is documented 1
• Retreatment should use a different antibiotic class (not another first-generation cephalosporin) for 7 days 2
• If symptoms persist or recur within 2 weeks, assume the organism is not susceptible to the original agent and select an alternative based on culture results 2

Common Pitfall to Avoid

The most dangerous error is assuming that oral cephalexin might work when parenteral cefazolin shows resistance simply because of different routes of administration—the resistance mechanism affects both drugs equally regardless of how they are delivered 1. Always respect susceptibility testing and choose an antibiotic from a different class when first-generation cephalosporin resistance is documented 2, 1.