What is the best treatment for a urinary tract infection (UTI) caused by Escherichia coli (E. coli) that produces Extended-Spectrum Beta-Lactamases (ESBL)?

Treatment of UTI Caused by ESBL-Producing E. coli

Intravenous fosfomycin is the preferred treatment for complicated UTIs caused by ESBL-producing E. coli, based on high-certainty evidence from randomized controlled trials showing equivalent efficacy to carbapenems with fewer ecological consequences. 1

First-line Treatment Options

For Complicated UTIs (with or without bacteremia):

1. Intravenous fosfomycin

   • High-certainty evidence supports its use for complicated UTIs with or without bacteremia 1
   • Caution in patients with heart failure risk (8.6% developed heart failure in the FOREST trial) 1
   • Contraindication: Patients with septic shock

2. Aminoglycosides (moderate-certainty evidence)

   • Plazomicin 15 mg/kg once daily 1
   • Amikacin (shown to be effective with 98% susceptibility in ESBL E. coli) 2
   • Recommended for shorter treatment courses (<7 days) due to nephrotoxicity risk 1

3. Carbapenems

   • Ertapenem 1g IV daily 3
   • Meropenem 1g three times daily 1
   • Consider as reserve agents to prevent resistance development

For Uncomplicated UTIs:

1. Fosfomycin trometamol

   • 3g single oral dose 4
   • 93% cure rate for cystitis caused by ESBL-producing E. coli 5

2. Beta-lactam/beta-lactamase inhibitor combinations (BLBLIs)

   • Moderate-certainty evidence supports their use 1
   • Amoxicillin-clavulanate: Effective for susceptible isolates (93% cure rate) but less effective (56%) for resistant isolates 5

Treatment Algorithm Based on UTI Severity

Step 1: Assess UTI Severity

• Uncomplicated lower UTI (cystitis): No systemic symptoms, no structural abnormalities
• Complicated UTI: Presence of structural abnormalities, male gender, pregnancy, immunosuppression, or ESBL-producing organisms 1
• Severe/bacteremic UTI: Systemic symptoms, sepsis, or bacteremia

Step 2: Select Appropriate Treatment

For Uncomplicated Lower UTI with ESBL-producing E. coli:

1. Oral fosfomycin 3g single dose
2. Amikacin (if susceptible)
3. Oral amoxicillin-clavulanate (if susceptible)

For Complicated UTI without Septic Shock:

1. IV fosfomycin (first choice)
2. Aminoglycosides for short-course therapy (≤7 days)
3. BLBLIs if susceptible
4. Carbapenems (reserve for severe cases or when other options are not available)

For Severe UTI/Bacteremia:

1. Carbapenems (meropenem, ertapenem)
2. Newer agents: Ceftazidime-avibactam, meropenem-vaborbactam 1

Step 3: Treatment Duration

• Uncomplicated UTI: 5-7 days
• Complicated UTI: 7-14 days (14 days for men when prostatitis cannot be excluded) 1
• Consider shorter duration (7 days) when patient is hemodynamically stable and afebrile for at least 48 hours 1

Risk Factors for ESBL-producing E. coli UTIs

Important to identify patients at risk for targeted empiric therapy:

• Recent hospitalization within 1 month 2, 6
• Prior antibiotic use within 3 months, especially fluoroquinolones, cephalosporins, and aminoglycosides 2, 6, 7
• Recurrent UTIs 1
• Presence of urinary catheter 7
• Pre-existing neurological diseases 6
• Diabetes mellitus 5
• Age over 60 years 5

Important Considerations and Pitfalls

1. Antimicrobial Stewardship:

   • Reserve carbapenems when possible to prevent further resistance development
   • Use targeted therapy based on susceptibility testing

2. Susceptibility Testing:

   • Always obtain urine culture before starting treatment
   • Adjust therapy based on susceptibility results

3. Common Pitfalls:

   • Using fluoroquinolones empirically (high resistance rates in ESBL-producing E. coli)
   • Failing to recognize risk factors for ESBL-producing organisms
   • Inadequate treatment duration for complicated infections
   • Not considering local antibiogram data

4. Special Considerations:

   • For patients with heart failure risk, avoid IV fosfomycin due to increased risk of heart failure 1
   • For patients with renal impairment, adjust dosing of aminoglycosides and monitor renal function

By following this evidence-based approach, clinicians can effectively treat UTIs caused by ESBL-producing E. coli while practicing appropriate antimicrobial stewardship to limit further resistance development.