ESBL-Producing Enterobacterales Are Susceptible to Ertapenem
Yes, ESBL-producing Enterobacterales remain susceptible to carbapenems, including ertapenem, and ertapenem is an effective treatment option for these infections. 1
Mechanism of Susceptibility
- ESBL-producing strains retain susceptibility to all carbapenems because carbapenems are stable against hydrolysis by extended-spectrum β-lactamases. 1
- Ertapenem is specifically stable against penicillinases, cephalosporinases, and extended-spectrum beta-lactamases, though it is hydrolyzed by metallo-beta-lactamases. 2
- In clinical studies, 93% of ESBL-producing Enterobacterales isolates tested susceptible to ertapenem. 3
Recommended Dosing for Adults with Normal Renal Function
For adults with normal renal function (creatinine clearance ≥31 mL/min/1.73 m²), the standard dose is ertapenem 1 gram IV once daily. 4, 2
- The once-daily dosing simplifies therapy compared to other carbapenems that require multiple daily doses. 4
- This dosing achieves adequate pharmacodynamic targets (≥75% T>MIC) for organisms with MIC ≤0.5 mg/L, which encompasses most ESBL-producers. 4
- Treatment duration is typically 7-14 days for soft tissue infections without osteomyelitis. 4
Clinical Efficacy Evidence
- Ertapenem demonstrates comparable or superior outcomes to other carbapenems (imipenem/meropenem) for ESBL-producing Enterobacterales infections. 4, 5
- A 2023 meta-analysis showed ertapenem was associated with significantly lower 30-day mortality (10.7% vs 17.7%) and shorter hospital stays compared to other carbapenems. 5
- Clinical response rates of 92% have been reported for ESBL-producing Gram-negative bacterial infections treated with ertapenem. 6
- A 2022 propensity-matched study found no difference in 30-day mortality between ertapenem and other carbapenems for ESBL bacteremia, even in patients with severe sepsis or septic shock. 7
When to Choose Ertapenem vs. Other Carbapenems
Ertapenem is preferred for:
- Moderate-severity infections where Pseudomonas aeruginosa and Enterococcus are not concerns (e.g., urinary tract infections, intra-abdominal infections with adequate source control). 4, 8
- Patients who are not critically ill or in septic shock. 9
- Situations requiring antimicrobial stewardship, as once-daily dosing improves compliance and ertapenem lacks anti-pseudomonal activity (reducing selection pressure). 4
Group 2 carbapenems (meropenem, imipenem, doripenem) are preferred for:
- Critically ill patients with high bacterial loads or septic shock. 8, 9
- Serious infections with elevated β-lactam minimum inhibitory concentrations. 9
- When Pseudomonas aeruginosa coverage is needed (ertapenem has NO activity against Pseudomonas). 4, 8
Important Limitations and Caveats
- Ertapenem does NOT cover Pseudomonas aeruginosa or Enterococcus species - alternative agents are required if these pathogens are suspected. 4, 8
- Ertapenem is hydrolyzed by metallo-β-lactamases; for MBL-producing organisms, use ceftazidime/avibactam plus aztreonam instead. 8, 2
- With 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. 4, 10
- Dose adjustment required for severe renal impairment: reduce to 0.5 grams every 24 hours when creatinine clearance ≤30 mL/min/1.73 m². 2
Antimicrobial Stewardship Considerations
- Carbapenems, including ertapenem, should be limited when other options are available to reduce selection pressure for carbapenem-resistant organisms. 4, 10
- In areas with high carbapenem-resistant Klebsiella pneumoniae prevalence, strongly consider carbapenem-sparing regimens for less severe infections. 8
- Reserve newer agents (ceftazidime/avibactam, ceftolozane/tazobactam) for multidrug-resistant infections to preserve their activity. 8