What is a suitable oral (PO) antibiotic regimen for Carbapenem-Resistant Enterobacteriaceae (CRE) infections?

Oral Antibiotic Regimens for Carbapenem-Resistant Enterobacteriaceae (CRE)

For uncomplicated urinary tract infections caused by CRE, a single dose of fosfomycin 3 g PO or nitrofurantoin 100 mg PO every 6 hours are the preferred oral treatment options. 1

Site-Specific Treatment Recommendations

Uncomplicated Urinary Tract Infections (UTIs)

• First-line options:
  • Fosfomycin 3 g PO single dose 1, 2
  • Nitrofurantoin 100 mg PO every 6 hours 1
• Alternative options:
  • Single-dose aminoglycoside (if susceptible) 1
  • High-dose ampicillin (if susceptible) or amoxicillin 500 mg PO every 8 hours (if susceptible) 1

Complicated UTIs

• Limited oral options are available
• Oral step-down therapy should be guided by susceptibility testing
• Potential options:
  • Fosfomycin 3 g PO every 48-72 hours (off-label for complicated UTIs) 3
  • Nitrofurantoin 100 mg PO every 6 hours (for lower UTI only, not for pyelonephritis) 1
  • Trimethoprim-sulfamethoxazole (if susceptible based on testing) 2

Treatment Algorithm Based on Infection Site and Severity

1. Identify infection site and severity

   • Uncomplicated UTI
   • Complicated UTI
   • Intra-abdominal infection
   • Bloodstream infection

2. Obtain susceptibility testing

   • Essential for guiding therapy
   • Consider antimicrobial synergy testing if available 1

3. For uncomplicated UTIs:

   • Use oral options as listed above
   • Duration: 3-5 days for cystitis 2

4. For complicated UTIs or other infections:

   • Start with IV therapy (ceftazidime-avibactam, meropenem-vaborbactam, polymyxin-based combinations)
   • Consider step-down to oral therapy based on susceptibility and clinical improvement
   • Duration: 7-14 days 1, 2

Important Considerations and Caveats

• Susceptibility testing is crucial: Treatment should be guided by antimicrobial susceptibility results 1

• Limited oral options: CRE infections often require initial IV therapy before step-down to oral options 1

• Combination therapy: For severe infections, combination therapy is often preferred over monotherapy, even when transitioning to oral options 1

• Monitoring: Close clinical monitoring is essential, with follow-up cultures to confirm microbiological clearance 2

• Resistance development: Be aware that resistance to fosfomycin can develop during treatment 3

• Site-specific considerations: Oral options are primarily validated for UTIs; other infection sites may require longer IV therapy before oral step-down 1

• Tigecycline limitations: Avoid tigecycline for bloodstream infections and pneumonia due to poor outcomes 1

Emerging Evidence

The treatment landscape for CRE is rapidly evolving. Recent guidelines suggest that for non-severe infections, particularly UTIs, oral options can be effective when chosen based on susceptibility testing 1. However, for severe infections, initial IV therapy with newer agents (ceftazidime-avibactam, meropenem-vaborbactam) followed by oral step-down therapy based on susceptibility is recommended 1.

For infections outside the urinary tract, oral options are more limited, and treatment decisions should be made in consultation with infectious disease specialists 1.