What is the best course of action for a patient with a urinary tract infection (UTI) whose urine culture shows resistance to cefazolin and who is currently being treated with Keflex (cephalexin)?

Immediate Action Required: Switch Antibiotics

If a urine culture shows resistance to cefazolin and the patient is currently on Keflex (cephalexin), you must discontinue cephalexin immediately and switch to an alternative antibiotic based on culture susceptibilities. Cephalexin and cefazolin share the same resistance profile—cefazolin is used as the surrogate marker for testing cephalexin susceptibility 1. Resistance to cefazolin definitively indicates cephalexin will be ineffective 1.

Why This Matters

• Cefazolin-cephalexin surrogate testing is the standard method recommended by CLSI and USCAST for determining cephalexin susceptibility 1
• Continuing ineffective therapy leads to treatment failure, persistent symptoms, and potential progression to upper tract infection or bacteremia 2, 3
• The patient is essentially receiving no effective antimicrobial coverage while on cephalexin if the organism is cefazolin-resistant 1

Immediate Management Steps

1. Review Culture Susceptibilities and Patient Context

• Obtain the complete antibiogram to identify which antibiotics the organism remains susceptible to 2, 3
• Assess infection severity: Does the patient have fever, flank pain, systemic symptoms, or signs of upper tract involvement? 2
• Determine if this is a complicated UTI by evaluating for obstruction, foreign body (catheter), diabetes, immunosuppression, male gender, pregnancy, or recent instrumentation 2

2. Select Appropriate Alternative Antibiotic

For uncomplicated cystitis (if organism susceptible):

• Nitrofurantoin 100 mg twice daily for 5 days (first-line option) 4, 5
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days (if local resistance <20% and organism susceptible) 4, 5
• Fosfomycin 3 g single dose (if available and organism susceptible) 4, 5

For complicated UTI or if first-line agents show resistance:

• Fluoroquinolones (if susceptible and local resistance <10%):
  • Ciprofloxacin 500-750 mg twice daily for 7 days 2, 3
  • Levofloxacin 750 mg once daily for 5-7 days 3
• Oral cephalosporins (if susceptible to higher-generation agents):
  • Cefpodoxime 200 mg twice daily for 10 days 3
  • Ceftibuten 400 mg once daily for 10 days 3
• Amoxicillin-clavulanate 875/125 mg twice daily for 7-14 days (if susceptible, though resistance rates can be high) 4

For severe infection requiring parenteral therapy:

• Ceftriaxone 1-2 g IV once daily 2, 3
• Cefepime 1-2 g IV every 12 hours 3
• Piperacillin-tazobactam 3.375-4.5 g IV every 6-8 hours 3
• Carbapenems (meropenem 1 g IV every 8 hours or imipenem 500 mg IV every 6 hours) if multidrug-resistant organism suspected 2, 3

3. Treatment Duration Considerations

• Uncomplicated cystitis in women: 3-7 days depending on agent selected 4, 5
• Complicated UTI: 7-14 days 2, 3
• Male patients: 14 days (when prostatitis cannot be excluded, which is most cases) 6
• Catheter-associated UTI: 7-14 days, with catheter replacement if in place ≥2 weeks 2, 3

Critical Pitfalls to Avoid

• Do not continue cephalexin even for "a few more days" while awaiting culture results—the organism is already proven resistant 1
• Do not use fluoroquinolones empirically if local resistance exceeds 10% or patient had recent fluoroquinolone exposure within 6 months 2, 3
• Do not use nitrofurantoin or fosfomycin if there are signs of upper tract involvement (fever, flank pain, systemic symptoms) as these agents have limited tissue penetration 3
• Do not treat asymptomatic bacteriuria in catheterized patients, as this promotes resistance without clinical benefit 2, 3

Special Considerations

If the patient is male:

• All UTIs in males are considered complicated 6
• Standard treatment duration is 14 days to cover potential prostatic involvement 6
• First-line options include trimethoprim-sulfamethoxazole or fluoroquinolones (if susceptible) 6

If multidrug-resistant organism (ESBL-producing or carbapenem-resistant):

• Consider newer β-lactam/β-lactamase inhibitor combinations: ceftazidime-avibactam 2.5 g IV every 8 hours or meropenem-vaborbactam 4 g IV every 8 hours 2, 3, 4
• Aminoglycosides (gentamicin 5 mg/kg once daily or amikacin 15 mg/kg once daily) may be appropriate for UTI-only infections 2, 3

If catheter-associated UTI:

• Replace catheter if it has been in place ≥2 weeks at treatment initiation, as this hastens symptom resolution and reduces recurrence 3
• Remove catheter entirely if no longer clinically necessary 2, 3

Follow-Up and Monitoring

• Reassess clinical response at 48-72 hours: Patient should be afebrile and showing symptom improvement 3
• If no improvement by 72 hours: Obtain repeat culture, consider imaging to evaluate for abscess or obstruction, and broaden antimicrobial coverage 3
• Consider follow-up urine culture after treatment completion if symptoms persist or in high-risk patients (pregnancy, immunosuppression, recurrent infections) 3