What is an appropriate treatment for recurrent Multidrug-resistant (MDR) Escherichia coli (E. coli) Urinary Tract Infections (UTIs)?

Treatment of Recurrent MDR E. coli UTIs

For recurrent multidrug-resistant (MDR) E. coli urinary tract infections (UTIs), fosfomycin is recommended as a first-line treatment option due to its effectiveness against MDR organisms and favorable resistance profile. 1, 2

First-Line Treatment Options

For Uncomplicated UTIs:

• Fosfomycin trometamol: 3g single dose oral administration 1, 2

  • Highly effective against MDR E. coli
  • FDA-approved specifically for uncomplicated UTIs due to E. coli
  • Low resistance rates (4.3%) compared to other antibiotics 3

• Nitrofurantoin: 100mg twice daily for 5 days 1

  • Excellent activity against MDR E. coli (resistance rates <1%) 3
  • Recommended by European Urology guidelines
  • Not suitable for patients with renal impairment

For Complicated UTIs:

• Ceftazidime-avibactam: 2.5g IV q8h 4

  • Recommended for complicated UTIs caused by carbapenem-resistant Enterobacterales (CRE)

• Meropenem-vaborbactam: 4g IV q8h or Imipenem-cilastatin-relebactam: 1.25g IV q6h 4, 5

  • Effective against MDR E. coli including ESBL-producing strains
  • Imipenem is specifically indicated for UTIs caused by E. coli 5

• Plazomicin: 15mg/kg IV q12h 4

  • Recommended for complicated UTIs due to CRE

Treatment Algorithm Based on UTI Type and Severity

1. For Simple Cystitis with MDR E. coli:

   • First choice: Fosfomycin 3g single dose 1, 2
   • Alternative: Nitrofurantoin 100mg twice daily for 5 days 1
   • If both contraindicated: Single-dose aminoglycoside 4

2. For Complicated UTIs with MDR E. coli:

   • First choice: Ceftazidime-avibactam 2.5g IV q8h 4
   • Alternatives: Meropenem-vaborbactam or Imipenem-cilastatin-relebactam 4, 5
   • For patients unable to tolerate above options: Plazomicin 15mg/kg IV q12h 4

3. For Recurrent UTIs Prevention:

   • Methenamine hippurate: 1g twice daily (non-antibiotic prophylaxis) 1
   • Low-dose post-coital antibiotic for UTIs related to sexual activity 1
   • Low-dose daily antibiotic for 6-12 months for UTIs unrelated to sexual activity 1

Special Considerations

• Antibiotic Resistance Patterns: Treatment should be guided by local antimicrobial susceptibility profiles 1

  • MDR E. coli often shows high resistance to ampicillin (66.9%), ciprofloxacin (49.9%), and trimethoprim-sulfamethoxazole 3
  • Avoid fluoroquinolones due to increasing resistance and side effects 1, 6

• Alternative Approaches:

  • Prolonged infusion of β-lactams for pathogens with high minimum inhibitory concentration (MIC) 4
  • Infectious disease consultation is highly recommended for MDR infections 4

• Emerging Options:

  • Doxycycline may be effective for susceptible MDR UTIs based on susceptibility testing 7
  • Natural isothiocyanates from plants like nasturtium and horseradish show promise against MDR E. coli in vitro 8

Monitoring and Follow-up

• Urine culture and susceptibility testing are essential to guide definitive therapy
• If persistence or reappearance of bacteriuria occurs after fosfomycin treatment, select alternative agents 2
• For recurrent infections, consider prophylactic options after acute episode resolves 1
• Periodic assessment of renal, hepatic, and hematopoietic function is advisable during prolonged therapy 5

Remember that treatment of MDR E. coli UTIs requires careful selection of antimicrobial agents based on susceptibility testing to improve clinical outcomes and prevent further resistance development.