What is the best treatment for multi-drug resistant Extended-Spectrum Beta-Lactamase (ESBL) Urinary Tract Infection (UTI)?

Best Treatment Options for Multi-Drug Resistant ESBL UTI

For complicated urinary tract infections caused by multi-drug resistant ESBL-producing organisms, carbapenems remain the most reliable option, but several carbapenem-sparing alternatives can be considered based on susceptibility testing, including ceftazidime-avibactam, fosfomycin, and aminoglycosides. 1

First-line Treatment Options

• Carbapenems: Remain the most reliable option for severe ESBL UTIs, especially in patients with sepsis or high-risk infections 1
• Ceftazidime-avibactam: Strongly recommended for complicated UTIs caused by ESBL and carbapenem-resistant Enterobacteriaceae (CRE) with high clinical cure rates (88.2%) and microbiological cure rates (71.5%) 1, 2
• Intravenous fosfomycin: Strong recommendation with high certainty of evidence for complicated UTIs without septic shock 1
• Aminoglycosides: Conditionally recommended for short-duration therapy in complicated UTIs without septic shock when susceptibility is confirmed 1

Alternative Options Based on Susceptibility

• Piperacillin-tazobactam or amoxicillin/clavulanic acid: Can be considered for low-risk, non-severe ESBL infections under antibiotic stewardship considerations 1
• Cotrimoxazole (Trimethoprim-sulfamethoxazole): May be considered for non-severe complicated UTIs if susceptibility is confirmed 1
• Nitrofurantoin: Effective for uncomplicated lower UTIs caused by ESBL-producing E. coli (93% sensitivity) but not appropriate for complicated UTIs or pyelonephritis 3
• Oral fosfomycin: Single 3g dose shows high efficacy (98% sensitivity) against ESBL E. coli for uncomplicated lower UTIs 3

Treatment Algorithm Based on Severity and Risk

For Severe Infections/Sepsis:

1. Initial therapy: Carbapenems (ertapenem, meropenem, imipenem) 1
2. Alternative: Ceftazidime-avibactam 2.5g IV q8h 1, 2

For Complicated UTI without Sepsis:

1. First choice: Intravenous fosfomycin (strong recommendation) 1
2. Alternatives:
   • Aminoglycosides for short duration if susceptible 1
   • Meropenem-vaborbactam or imipenem-cilastatin-relebactam 1
   • Plazomicin 15 mg/kg IV q12h 1

For Uncomplicated Lower UTI:

1. First choice: Nitrofurantoin or oral fosfomycin if susceptible 3
2. Alternative: Single-dose aminoglycoside 1

Step-down Therapy

• Once patients are stabilized on initial therapy, step-down to targeted oral therapy based on susceptibility testing is recommended 1
• Options include:
  • Older β-lactam/β-lactamase inhibitors 1
  • Quinolones (if susceptible) 1
  • Cotrimoxazole (if susceptible) 1

Duration of Therapy

• 10-14 days for complicated UTI or pyelonephritis 4
• Clinical response should be evident within 48-72 hours of appropriate therapy 4

Important Caveats and Pitfalls

• Avoid tigecycline: Strong recommendation against use for ESBL infections due to very low certainty of evidence 1
• Avoid cephamycins and cefepime: Conditional recommendation against use for ESBL infections 1
• Reserve newer β-lactam/β-lactamase inhibitor combinations: These should be preserved for extensively resistant bacteria rather than routine ESBL infections 1
• Susceptibility testing is crucial: Treatment should always be guided by antimicrobial susceptibility results 1
• Consider infectious disease consultation: Highly recommended for management of infections caused by multidrug-resistant organisms 1
• Address underlying urological abnormalities: Mandatory for successful treatment of complicated UTIs 4

Special Considerations for Carbapenem-Resistant Infections

• For carbapenem-resistant Enterobacteriaceae (CRE) causing UTIs, options include:
  • Ceftazidime-avibactam 1
  • Meropenem-vaborbactam or imipenem-cilastatin-relebactam 1
  • Plazomicin 1
  • For MBL-producing CRE: Ceftazidime-avibactam plus aztreonam or cefiderocol 1

By following this evidence-based approach and selecting antimicrobial therapy based on susceptibility patterns, severity of infection, and patient-specific factors, optimal outcomes can be achieved while practicing good antimicrobial stewardship.