What is the role of oral ertapenem (a carbapenem antibiotic) in treating infections caused by Extended-Spectrum Beta-Lactamase (ESBL)-producing organisms?

Role of Oral Ertapenem in Treating ESBL-Producing Infections

Ertapenem is not available in oral formulation and can only be administered intravenously or intramuscularly for treating infections caused by ESBL-producing organisms. 1

Available Formulations and Administration

• Ertapenem is only FDA-approved as an injectable carbapenem antibiotic available for:
  • Intravenous (IV) administration
  • Intramuscular (IM) administration
• Standard dosing is 1g once daily in adults 1
• No oral formulation exists, which is a key limitation compared to some other antibiotics

Efficacy Against ESBL-Producing Organisms

Ertapenem demonstrates excellent activity against ESBL-producing Enterobacteriaceae:

• Highly effective against common ESBL-producing pathogens including:
  • Escherichia coli
  • Klebsiella pneumoniae
  • Proteus mirabilis 1, 2
• Stable against hydrolysis by various beta-lactamases including ESBLs 1
• Clinical studies show 91% positive outcomes when used for ESBL infections 2
• A 2023 meta-analysis found ertapenem was associated with lower 30-day mortality compared to other carbapenems (10.7% vs 17.7%) in ESBL infections 3

Clinical Applications

Ertapenem is particularly valuable in several scenarios:

1. Complicated urinary tract infections:

   • European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines support ertapenem use for complicated UTIs caused by ESBL-producing organisms 4
   • Studies show high efficacy in pediatric patients with complicated UTIs caused by ESBL-producing bacteria 5, 6

2. Step-down therapy:

   • Excellent option for consolidation therapy after initial treatment with other antibiotics 2
   • Can be used for outpatient parenteral antibiotic therapy (OPAT) due to once-daily dosing

3. Diabetic foot infections:

   • IDSA guidelines recommend ertapenem for moderate to severe diabetic foot infections when ESBL-producing organisms are suspected 4

Advantages Over Other Carbapenems

• Once-daily dosing (compared to multiple daily doses for imipenem/meropenem) 1
• Lower selection pressure for resistant Pseudomonas aeruginosa and Acinetobacter species (as ertapenem lacks activity against these organisms) 7
• Shorter hospital stays compared to other carbapenems (mean difference of 6.02 days) 3
• Comparable clinical cure rates to other carbapenems 3

Limitations

• No oral formulation available - the most significant limitation 1
• Lacks activity against Pseudomonas aeruginosa and Acinetobacter species 8
• Not suitable for central nervous system infections
• Cannot be used when these non-fermenting gram-negative organisms are suspected

Alternative Oral Options for ESBL Infections

Since oral ertapenem does not exist, alternative oral options for ESBL infections include:

1. Fluoroquinolones (if susceptible):

   • Can be used as step-down therapy in stable patients 4
   • However, increasing resistance rates limit empiric use 8

2. Fosfomycin:

   • Oral fosfomycin has been compared with ertapenem for outpatient therapy in non-bacteremic UTIs caused by ESBL-producing Enterobacteriaceae 4
   • Limited evidence supports its use (very low certainty of evidence) 4

Conclusion

Ertapenem is a valuable carbapenem for treating ESBL-producing infections, but it is critically important to understand that it is only available as an injectable formulation. When oral therapy is required for ESBL infections, clinicians must select alternative agents based on susceptibility testing.