What is the recommended treatment for a urinary tract infection (UTI) caused by an Extended-Spectrum Beta-Lactamase (ESBL)-producing organism?

Treatment of UTIs Caused by ESBL-Producing Organisms

For UTIs caused by ESBL-producing organisms, carbapenems are the first-line treatment option, with ertapenem 1g IV daily being the preferred choice due to its once-daily dosing and excellent coverage against ESBL-producing organisms. 1

Treatment Algorithm Based on Infection Severity

Uncomplicated Lower UTI with ESBL-Producing Organism

1. First-line oral options (if susceptible):

   • Nitrofurantoin 100mg twice daily for 5-7 days 2, 3, 4, 5
   • Fosfomycin 3g single dose 2, 3, 4
   • Pivmecillinam (if available) 2, 3

2. Second-line options (based on susceptibility):

   • Amoxicillin-clavulanate (for ESBL-E. coli only) 2
   • Trimethoprim-sulfamethoxazole (only if susceptibility confirmed) 6

Complicated UTI or Pyelonephritis with ESBL-Producing Organism

1. First-line parenteral options:

   • Ertapenem 1g IV daily 1, 7
   • Meropenem 1g IV three times daily 6
   • Imipenem-cilastatin 0.5g IV three times daily 6

2. Alternative parenteral options (based on susceptibility):

   • Amikacin 15 mg/kg daily (with drug level monitoring) 6, 1
   • Ceftazidime-avibactam 2.5g IV three times daily 6, 2
   • Ceftolozane-tazobactam 1.5g IV three times daily 6, 2
   • Meropenem-vaborbactam 2g IV three times daily 6, 2
   • Cefiderocol 2g IV three times daily 6, 1

Treatment Duration

• Uncomplicated lower UTI: 5-7 days 1
• Complicated UTI: 7-14 days 6
• Pyelonephritis: 10-14 days 1
• For men, consider extending to 14 days when prostatitis cannot be excluded 6

Important Considerations

Carbapenem-Sparing Approach

The European Association of Urology (EAU) guidelines recommend considering carbapenem-sparing treatments in settings with high incidence of carbapenem-resistant Klebsiella pneumoniae 6. Nitrofurantoin has shown comparable effectiveness to carbapenems for lower UTIs caused by ESBL-producing organisms in a recent 2025 multicenter cohort study 5.

Susceptibility Testing

Always obtain urine cultures and susceptibility testing before initiating treatment for suspected ESBL infections 6. Initial empiric therapy should be tailored based on local resistance patterns and specific host factors 6.

De-escalation

When clinical improvement is observed and susceptibility results are available, consider de-escalation to a suitable oral option to reduce the risk of developing carbapenem resistance 1.

Monitoring

• Assess for resolution of symptoms (dysuria, frequency, urgency) within 48-72 hours 1
• Monitor for fever resolution within 48-72 hours 1
• Consider follow-up urine culture after completion of therapy 1

Common Pitfalls

• Failing to consider local resistance patterns when selecting empiric therapy
• Using fluoroquinolones empirically in areas with >10% resistance rates 6
• Not adjusting antibiotic doses based on renal function
• Prolonged carbapenem use when de-escalation is possible
• Inappropriate initial therapy is associated with increased mortality in ESBL infections 1

By following this evidence-based approach, clinicians can effectively manage UTIs caused by ESBL-producing organisms while practicing good antimicrobial stewardship.