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

Treatment of ESBL Urinary Tract Infections

Carbapenems are the first-line treatment for serious ESBL urinary tract infections, while carbapenem-sparing alternatives should be considered for less severe infections to reduce selection pressure for carbapenem resistance. 1

First-Line Treatment Options Based on Severity

Severe Infections/Septic Shock

• Group 2 carbapenems (imipenem/cilastatin, meropenem, doripenem) are preferred for critically ill patients with high bacterial loads or elevated β-lactam MICs 1
• Ertapenem (1g IV daily) is an effective option for ESBL UTIs and can be administered intravenously or subcutaneously, even in outpatient settings 2, 3
• Ertapenem is FDA-approved for complicated urinary tract infections including pyelonephritis due to Escherichia coli, including cases with concurrent bacteremia, or Klebsiella pneumoniae 4

Moderate Infections

• Piperacillin/tazobactam may be considered for stable patients with mild to moderate infections 1, 5
• Intravenous fosfomycin has shown high-certainty evidence for treatment of complicated UTIs with or without bacteremia 5
• Aminoglycosides (including plazomicin) can be effective for cUTI caused by ESBL-producing organisms, but duration should be limited to avoid nephrotoxicity 5
• Ceftolozane/tazobactam and ceftazidime/avibactam are newer options that can preserve carbapenems 1, 6

Mild Infections/Uncomplicated UTIs

• Oral options for ESBL-E. coli UTIs include:
  • Nitrofurantoin (5-day course) 6, 7, 8
  • Fosfomycin tromethamine (3g single dose) 6, 7, 8
  • Pivmecillinam (5-day course) 6, 8
• Single-dose aminoglycoside therapy can be effective for simple cystitis due to ESBL-producing organisms 5

Special Considerations

Resistance Patterns

• Treatment selection should consider local epidemiology of resistance 5, 1
• In areas with high carbapenem-resistant Klebsiella pneumoniae, carbapenem-sparing regimens are strongly recommended 5
• Fluoroquinolones should be avoided in regions with fluoroquinolone resistance rates >20% among E. coli isolates and should generally be reserved for patients with beta-lactam allergies 5, 1

Emerging Options

• Newer agents like ceftolozane/tazobactam and ceftazidime/avibactam should be reserved for multidrug-resistant infections to preserve their activity 1
• Meropenem-vaborbactam and imipenem-cilastatin-relebactam are recommended for complicated UTIs caused by carbapenem-resistant Enterobacteriaceae (CRE) 5

Common Pitfalls to Avoid

• Overuse of carbapenems leads to selection pressure and emergence of carbapenem-resistant organisms 1
• Extended use of cephalosporins should be discouraged in settings with high incidence of ESBL-producing Enterobacteriaceae 5
• Extended use of fluoroquinolones should be discouraged because of selective pressure (mainly for ESBL-producing Enterobacteriaceae) 5

Treatment Duration

• For uncomplicated UTIs, short courses (3-5 days) of appropriate antibiotics are sufficient 5, 6
• For complicated UTIs, treatment duration should be guided by clinical response, with typical courses lasting 7-14 days 5

Monitoring

• Patients should be reassessed when microbiological testing results are available, and antimicrobial de-escalation or withdrawal should be considered when appropriate 5
• Follow-up urine cultures may be useful to confirm microbiological cure, especially in complicated cases 3