Does Ertapenem Cover ESBL?
Yes, ertapenem provides effective coverage against Extended-Spectrum Beta-Lactamase (ESBL)-producing Enterobacteriaceae and is FDA-approved for this indication. 1
Mechanism and Spectrum of Activity
Ertapenem is stable against hydrolysis by extended-spectrum beta-lactamases, making it inherently active against ESBL-producing organisms 1. The FDA label explicitly states that ertapenem is stable against "penicillinases, cephalosporinases and extended spectrum beta-lactamases" 1.
The drug demonstrates bactericidal activity through inhibition of cell wall synthesis by binding to penicillin-binding proteins (PBPs). 1
Clinical Evidence Supporting ESBL Coverage
Guideline Recommendations
The 2022 ESCMID guidelines for multidrug-resistant gram-negative bacilli indicate that ertapenem shows similar or better outcomes compared to imipenem/meropenem for third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE) bloodstream infections, which includes ESBL producers 2. One randomized controlled trial found significantly lower mortality with ertapenem compared to other carbapenems 2.
The 2017 WSES guidelines classify ertapenem as a Group 1 carbapenem with activity against ESBL-producing pathogens, though noting it lacks activity against Pseudomonas aeruginosa and Enterococcus species 2.
Clinical Efficacy Data
Research demonstrates strong clinical outcomes:
- 93% of ESBL-producing Enterobacteriaceae isolates were susceptible to ertapenem in a tertiary care study 3
- 91% clinical efficacy rate when used for ESBL infections, with 85.7% microbiologic cure 4
- 78% clinical response and 92% microbiologic cure when used as first-line treatment for ESBL infections 5
Important Caveats and Limitations
Organisms NOT Covered
Ertapenem does NOT cover:
- Pseudomonas aeruginosa 2
- Enterococcus species 2
- Methicillin-resistant Staphylococcus aureus 1
- Organisms producing metallo-beta-lactamases (MBLs) 1
Resistance Considerations
When using newer MIC interpretive breakpoints, an additional 12% of ESBL-producing K. pneumoniae and 27% of Enterobacter cloacae isolates may be classified as non-susceptible to ertapenem 6. This highlights the importance of:
- Confirming susceptibility testing before definitive therapy
- Using EUCAST breakpoint of ≤0.5 mg/L for E. coli 7
- Maintaining target free plasma concentration ≥4× MIC 7
Clinical Context for Use
Ertapenem is most appropriate for:
- Community-acquired infections with ESBL organisms 8
- Consolidation therapy after initial treatment with broader carbapenems 4
- Infections where Pseudomonas and Enterococcus are not concerns 2
- Urinary tract infections (40-47% of patients in clinical studies) 2
The ESCMID guidelines recommend limiting carbapenem use, including ertapenem, when other options are available against ESBL-producing Enterobacteriaceae to preserve this antibiotic class 7. However, when carbapenems are indicated, ertapenem remains an effective choice for susceptible ESBL organisms.
Practical Prescribing Points
The once-daily dosing of ertapenem (1g IV daily in adults) provides a practical advantage over other carbapenems requiring multiple daily doses 1, 8. For pediatric patients 3 months to 12 years, use 15 mg/kg IV; for those 13-17 years, use 20 mg/kg up to maximum 1g 1.
Monitor for development of resistance during therapy, as one case report documented emergence of ertapenem-resistant E. coli during treatment 4. Isolates with low-level ertapenem resistance may retain susceptibility to imipenem/meropenem, while high-level resistance typically confers cross-resistance to all carbapenems 3.