What is the recommended treatment for urinary tract infections (UTI) resistant to antibiotics?

Treatment for Antibiotic-Resistant Urinary Tract Infections

For urinary tract infections resistant to antibiotics, carbapenems and novel broad-spectrum antimicrobial agents should be used based on culture results indicating multidrug-resistant organisms, with specific agents selected according to local resistance patterns. 1

Treatment Algorithm for Antibiotic-Resistant UTIs

Step 1: Identify Type of Resistance and UTI Classification

• Complicated UTI factors:

  • Obstruction in urinary tract
  • Foreign body presence
  • Incomplete voiding
  • Male gender
  • Pregnancy
  • Diabetes mellitus
  • Immunosuppression
  • Healthcare-associated infections
  • ESBL-producing organisms
  • Multidrug-resistant organisms 1

• Obtain cultures before initiating therapy to guide targeted treatment

Step 2: Select Appropriate Treatment Based on Resistance Pattern

For Carbapenem-Resistant Enterobacterales (CRE) UTIs:

1. For complicated UTIs due to CRE:

   • Ceftazidime-avibactam 2.5 g IV q8h 1
   • Meropenem-vaborbactam 4 g IV q8h 1
   • Imipenem-cilastatin-relebactam 1.25 g IV q6h 1
   • Plazomicin 15 mg/kg IV q12h 1

2. For simple cystitis due to CRE:

   • Single-dose aminoglycoside 1
   • Fosfomycin 3 g PO single dose (for susceptible organisms) 2, 3

For ESBL-producing Enterobacterales:

1. For E. coli with ESBL:

   • Nitrofurantoin
   • Fosfomycin
   • Carbapenems 3

2. For Klebsiella pneumoniae with ESBL:

   • Fosfomycin
   • Carbapenems 3

For Multidrug-Resistant Pseudomonas aeruginosa:

1. If susceptible to specific agents:

   • Ceftolozane/tazobactam 1.5-3 g IV q8h
   • Ceftazidime/avibactam 2.5 g IV q8h
   • Imipenem/cilastatin/relebactam 1.25 g IV q6h 1

2. If extensively resistant:

   • Colistin monotherapy or combination therapy 1

Step 3: Determine Treatment Duration

• Uncomplicated UTI: 5-7 days
• Complicated UTI: 7-14 days (depending on severity and response) 1
• Pyelonephritis: 7-14 days 1

Evidence-Based Recommendations for Specific Agents

Meropenem-Vaborbactam

Meropenem-vaborbactam has shown superior efficacy compared to piperacillin-tazobactam in the TANGO I trial, with overall success rates of 98.4% vs 94.0% 4, 5. This agent is particularly effective against KPC-producing CRE, which represents one of the most clinically relevant carbapenemases in many regions 5.

Ceftazidime-Avibactam

This agent is effective against most KPC-producing CRE strains but should be used with caution for KPC-3 producers, where combination with a carbapenem may be considered 1.

Fosfomycin

Fosfomycin has a unique mechanism of action that generally avoids cross-resistance with other antibiotic classes. It achieves high urinary concentrations and is bactericidal in urine at therapeutic doses 2. The recommended dose for uncomplicated UTIs is a single 3g sachet mixed with water 2.

Aminoglycosides

Aminoglycosides are ideal for UTI treatment as they achieve urinary concentrations 25-100 times higher than plasma levels. Single-dose aminoglycoside therapy has shown high microbiologic cure rates (87-100%) for lower UTIs 1.

Important Clinical Considerations

1. Always base treatment on local resistance patterns when selecting empiric therapy 1

2. Address underlying urological abnormalities - management of anatomic or functional issues is mandatory for successful treatment 1

3. Avoid fluoroquinolones when local resistance exceeds 10% 1

4. Reserve carbapenems and novel agents for confirmed multidrug-resistant infections to prevent further resistance development 1, 3

5. Consider renal function when dosing medications, particularly with agents like fosfomycin where elimination is significantly decreased in renal impairment 2

6. Monitor for adverse effects - headache is the most common side effect with meropenem-vaborbactam 5

By following this structured approach to antibiotic-resistant UTIs, clinicians can optimize treatment outcomes while practicing antimicrobial stewardship to limit further resistance development.