What antibiotics can be used as prophylaxis in a patient with carbapenem-resistant (CR) Klebsiella urinary tract infection (UTI) undergoing ureteroscopy?

Antibiotic Prophylaxis for Ureteroscopy in Patients with Carbapenem-Resistant Klebsiella UTI

For patients with carbapenem-resistant Klebsiella urinary tract infection undergoing ureteroscopy, the most appropriate prophylactic antibiotic regimen should be based on in vitro susceptibility testing, with ceftazidime-avibactam, meropenem-vaborbactam, or imipenem-cilastatin-relebactam as preferred options if susceptible, or aminoglycosides as alternatives when these newer agents are not available or not susceptible. 1

First-Line Options (Based on Susceptibility Testing)

Newer β-lactam/β-lactamase Inhibitor Combinations

• Ceftazidime-avibactam (2.5 g IV) 1

  • Effective against KPC-producing CRE
  • Weak recommendation, very low quality of evidence
  • Resistance can develop, especially with prior exposure

• Meropenem-vaborbactam (4 g IV) 1

  • FDA-approved for complicated UTIs
  • Demonstrated efficacy in TANGO-II trial for CRE infections
  • Weak recommendation, low quality of evidence

• Imipenem-cilastatin-relebactam (1.25 g IV) 1

  • Active against most KPC-producing CRE strains
  • Weak recommendation, low quality of evidence
  • Not effective against metallo-β-lactamase producers

Alternative Options

Aminoglycosides

• Single-dose aminoglycoside (e.g., amikacin) 1, 2

  • Ideal for UTI due to high urinary concentrations
  • Particularly effective when the isolate shows in vitro susceptibility
  • Weak recommendation, very low quality of evidence
  • MIC values within susceptible range do not influence outcomes 2

• Plazomicin (15 mg/kg IV) 1

  • Novel aminoglycoside with activity against many CRE strains
  • Stable against many aminoglycoside-modifying enzymes
  • Weak recommendation, very low quality of evidence

Decision Algorithm Based on Infection Severity and Susceptibility

1. For non-severe infections or low-risk patients:

   • Use monotherapy with the least resistant antibiotic based on MICs relative to breakpoints 1
   • Consider older antibiotics that show in vitro activity (good practice statement, expert opinion) 1

2. For severe infections or high-risk patients:

   • Consider combination therapy with two in vitro active drugs 1
   • For metallo-β-lactamase producers resistant to newer agents, aztreonam plus ceftazidime-avibactam combination may be effective 1

Important Considerations

Susceptibility Testing

• Comprehensive susceptibility testing is crucial before selecting prophylactic antibiotics
• Consider testing for fosfomycin susceptibility, as it shows high efficacy against CRE in urinary infections 3
• For pan-resistant CRE, use the least resistant antibiotic based on MICs relative to breakpoints 1

Risk Factors to Consider

• Advanced age, comorbidities, previous antibiotic use, and prolonged catheterization increase risk of treatment failure 4
• Recent antibiotic exposure increases risk of resistant infections 5

Common Pitfalls to Avoid

1. Avoid empiric use of fluoroquinolones due to high resistance rates in many communities 5
2. Avoid tigecycline for UTIs due to poor urinary concentrations 1
3. Use caution with colistin combinations due to high nephrotoxicity risk, especially when combined with aminoglycosides 2
4. Don't delay appropriate therapy - CRE infections have high mortality rates when treated inappropriately

Special Situations

For Metallo-β-lactamase Producers

• Consider aztreonam plus ceftazidime-avibactam combination therapy 1
• Cefiderocol may be an option for severe infections due to metallo-β-lactamase producers 1

For Pan-Resistant Isolates

• Consider combination therapy with multiple agents showing the lowest MICs relative to breakpoints 1
• Fosfomycin has shown high efficacy ratios against CRE causing UTIs and may be considered 3

By following this algorithm and selecting antibiotics based on susceptibility testing, you can provide effective prophylaxis for patients with carbapenem-resistant Klebsiella UTI undergoing ureteroscopy while minimizing the risk of treatment failure and further resistance development.