What carbapenems (antibiotics) are effective against Extended-Spectrum Beta-Lactamase (ESBL)-producing bacteria?

Carbapenem Coverage for ESBL-Producing Organisms

All carbapenems—ertapenem, imipenem, and meropenem—provide effective coverage against ESBL-producing Enterobacteriaceae, with ertapenem showing similar or better outcomes compared to imipenem/meropenem for bloodstream infections. 1

Group 1 Carbapenem: Ertapenem

Ertapenem is highly effective against ESBL-producing Enterobacteriaceae and represents a carbapenem-sparing option when Pseudomonas and Enterococcus coverage is not required. 2, 1

Spectrum of Activity

• Covers: ESBL-producing E. coli, Klebsiella pneumoniae, Proteus mirabilis, and other Enterobacteriaceae 1, 3
• Does NOT cover: Pseudomonas aeruginosa or Enterococcus species 2, 1
• Does NOT cover: Acinetobacter baumannii 4

Clinical Efficacy Data

• In ESBL-positive gram-negative bacteremia, ertapenem achieved 96% favorable clinical response with only 4% attributable mortality 4
• Among 205 ESBL-producing Enterobacteriaceae isolates, 93% were susceptible to ertapenem 5
• Ertapenem demonstrates similar or better outcomes compared to imipenem/meropenem for third-generation cephalosporin-resistant Enterobacteriaceae bloodstream infections 2, 1

Critical Resistance Considerations

• When using newer CLSI 2010 MIC breakpoints, an additional 12% of ESBL-producing K. pneumoniae and 27% of Enterobacter cloacae may be classified as non-susceptible 1
• Isolates with low-level ertapenem resistance typically retain susceptibility to imipenem and meropenem, while high-level ertapenem resistance predicts resistance to all carbapenems 5

Optimal Clinical Scenarios for Ertapenem

• Urinary tract infections caused by ESBL producers where Pseudomonas is not a concern 1
• Culture-guided step-down therapy after initial broad-spectrum treatment 4
• Community-acquired infections with documented ESBL organisms 5

Group 2 Carbapenems: Imipenem and Meropenem

Imipenem and meropenem provide broader coverage than ertapenem, including activity against Pseudomonas aeruginosa and most Enterococcus species. 2, 6

Spectrum of Activity

• Cover: All organisms covered by ertapenem PLUS Pseudomonas aeruginosa 2, 7, 6
• Cover: Enterococcus faecalis (imipenem has inhibitory activity against enterococci) 7, 6
• Do NOT cover: Enterococcus faecium, Stenotrophomonas maltophilia, methicillin-resistant staphylococci 7, 6

Comparative In Vitro Activity

• Imipenem demonstrates somewhat greater activity against aerobic gram-positive cocci compared to meropenem 6
• Meropenem demonstrates somewhat greater activity against aerobic gram-negative bacilli compared to imipenem 6
• Both achieve >97% likelihood of maintaining free drug concentrations above MIC for adequate duration against ESBL producers 8

Clinical Efficacy Against ESBL Producers

• All ESBL-producing isolates susceptible to ertapenem were also susceptible to imipenem and meropenem 5
• In comparative studies, 100% of ESBL-producing isolates were susceptible to imipenem and 97% to meropenem 8
• Both agents showed high in vitro efficacy with MIC90 values of 0.25-0.5 μg/mL for ESBL-positive Enterobacteriaceae 9

When to Choose Imipenem/Meropenem Over Ertapenem

• Polymicrobial infections where Pseudomonas aeruginosa or Enterococcus coverage is needed 2
• Nosocomial pneumonia or ventilator-associated pneumonia with risk of Pseudomonas 2
• Severe sepsis or septic shock requiring broadest empiric coverage before culture results 4
• Intra-abdominal infections with potential for Enterococcus involvement 2

Mechanism of Action and Stability

All carbapenems inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins, with imipenem showing strong affinity for PBPs 1a, 1b, 2,3,4, and 5. 7

• Stable against hydrolysis by penicillinases, cephalosporinases, and extended-spectrum beta-lactamases 3, 7
• Hydrolyzed by metallo-beta-lactamases, which represent an important resistance mechanism 3

Critical Pitfalls to Avoid

• Do not use ertapenem when Pseudomonas aeruginosa or Enterococcus coverage is required—this will result in treatment failure 2, 1
• Resistance can emerge during treatment of Pseudomonas infections with any carbapenem, requiring surveillance cultures 6
• Limit carbapenem use when other effective options exist to preserve this antibiotic class and reduce selective pressure for carbapenem-resistant Enterobacteriaceae 1, 10
• Avoid empiric ertapenem in critically ill patients with unknown source until Pseudomonas and Enterococcus are excluded 4