Is ertapenem a good coverage option for Extended-Spectrum Beta-Lactamase (ESBL) producing Escherichia coli (E coli) that is sensitive to ertapenem?

Ertapenem for ESBL E. coli Treatment

Ertapenem is an excellent treatment option for ESBL-producing E. coli that is confirmed to be sensitive to ertapenem, providing effective coverage with the advantage of once-daily dosing. 1, 2

Efficacy Against ESBL E. coli

• Ertapenem has demonstrated strong activity against ESBL-producing Enterobacteriaceae, including E. coli 3
• The FDA label confirms ertapenem's activity against E. coli, though it specifically notes "excluding ESBL producing isolates" for some other Enterobacteriaceae 2
• When susceptibility testing confirms sensitivity to ertapenem, clinical outcomes are favorable:
  • 91% positive clinical outcomes in a case series of ESBL infections 4
  • 96% favorable clinical response in patients with multidrug-resistant gram-negative bacteremia (79% ESBL-producers) 5

Pharmacodynamic Considerations

• Once-daily dosing with 1g of ertapenem is bactericidal against ESBL-producing E. coli with MICs ≤0.5 mg/L 6
• For strains with MICs of 1.0 mg/L, ertapenem can still be bactericidal but regrowth may occur in some strains 6
• Higher dosing (2g daily) may be considered for strains with MICs of 1.0 mg/L to ensure adequate coverage 6

Clinical Application

• Ertapenem is specifically recommended for community-acquired infections with ESBL producers at a dose of 1g IV every 24 hours 1
• The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines note that ertapenem has shown similar or better outcomes compared to imipenem/meropenem for 3rd generation cephalosporin-resistant Enterobacterales bloodstream infections 3

Important Considerations and Caveats

1. Confirm susceptibility testing results: Always verify that the isolate is truly susceptible to ertapenem before initiating therapy 1

2. MIC interpretation: Be aware that updated breakpoints for carbapenems have resulted in more isolates being classified as non-susceptible to ertapenem 3

   • In Taiwan, an additional 12% of ESBL-producing K. pneumoniae isolates were reclassified as not susceptible to ertapenem when new MIC interpretive breakpoints were applied 3

3. Resistance development: Monitor for development of resistance during therapy

   • One case report noted development of ertapenem-resistant E. coli during treatment 4

4. Advantages over other carbapenems:

   • Once-daily dosing convenience 7
   • May have less potential to select for carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa since ertapenem lacks activity against these organisms 5

5. Alternative options if ertapenem resistance develops:

   • Meropenem 1g IV every 8 hours (extended or continuous infusion preferred) for severe infections 1
   • Piperacillin-tazobactam may be considered for non-severe infections when the MIC is ≤4 mg/L 1
   • Aminoglycosides for urinary tract infections when susceptible 1

In summary, ertapenem provides effective coverage against ESBL-producing E. coli when susceptibility is confirmed, with the practical advantage of once-daily dosing that may facilitate outpatient parenteral antibiotic therapy in appropriate cases.