What is Ertapenem?
Ertapenem is a Group 1 carbapenem antibiotic with broad-spectrum activity against gram-positive, gram-negative aerobic bacteria, and anaerobes, but notably lacks reliable activity against Pseudomonas aeruginosa and Enterococcus species. 1
Chemical Structure and Classification
Ertapenem is a sterile, synthetic, parenteral 1-β methyl-carbapenem structurally related to beta-lactam antibiotics 2. It is chemically described as a monosodium salt with molecular weight 497.50 and empirical formula C22H24N3O7SNa 2. The drug is supplied as a sterile lyophilized powder containing 1 gram ertapenem (equivalent to 1.046 grams ertapenem sodium) with approximately 137 mg sodium content 2.
Mechanism of Action
Like other beta-lactams, ertapenem inhibits bacterial cell wall synthesis by binding to and inhibiting penicillin-binding proteins 3. It exhibits time-dependent killing and demonstrates resistance to nearly all beta-lactamases, including extended-spectrum beta-lactamases (ESBLs) and AmpC enzymes 4, 5. This resistance profile makes it particularly valuable against multidrug-resistant organisms 3.
Antimicrobial Spectrum
Organisms Covered:
- Gram-negative bacteria: Enterobacteriaceae (including ESBL-producing pathogens) with MIC90s for most species <1 mg/L 6
- Gram-positive bacteria: Streptococcus pneumoniae and methicillin-susceptible Staphylococcus aureus 6, 7
- Anaerobes: Most Bacteroides fragilis group isolates (MIC90s 1-4 mg/L) and Clostridium species 6
Organisms NOT Covered:
- Pseudomonas aeruginosa 1, 4
- Enterococcus species 1, 4
- Methicillin-resistant staphylococci (MRSA) 6
- Other non-fermentative gram-negative bacteria commonly associated with nosocomial infections 4
Pharmacokinetics
Ertapenem has a unique extended half-life of approximately 4 hours due to extensive protein binding, allowing for once-daily dosing 4, 5. Following a 1 g intravenous infusion, it achieves a Cmax of 155 mg/L for total drug and 13 mg/L for free drug 5. The drug exhibits non-linear pharmacokinetics due to concentration-dependent plasma protein binding 2. Excretion is largely renal, divided equally between native drug and an open-ring derivative 5.
FDA-Approved Indications
Ertapenem is indicated for moderate to severe infections in adults and pediatric patients ≥3 months of age 2:
- Complicated intra-abdominal infections 2
- Complicated skin and skin structure infections, including diabetic foot infections without osteomyelitis 2
- Community-acquired pneumonia 2
- Complicated urinary tract infections including pyelonephritis 2
- Acute pelvic infections (postpartum endomyometritis, septic abortion, post-surgical gynecologic infections) 2
- Prophylaxis of surgical site infection following elective colorectal surgery (adults only) 2
Clinical Positioning
Ertapenem is classified as a Group 1 carbapenem, distinguishing it from Group 2 carbapenems (imipenem/cilastatin, meropenem, doripenem) which have activity against non-fermentative gram-negative bacilli 1. This narrower spectrum makes ertapenem better suited for community-acquired infections rather than nosocomial infections 3, 4.
Comparative Efficacy:
Studies comparing ertapenem versus imipenem/meropenem for third-generation cephalosporin-resistant Enterobacterales bloodstream infections showed similar or better outcomes with ertapenem, though it was often used for less severe infections 1. The overall certainty of evidence showing similar outcomes between ertapenem and broader-spectrum carbapenems was moderate 1.
Dosing Considerations
Adults:
- Standard dose: 1 g every 24 hours intravenously or intramuscularly 2
- Dosage adjustment required for creatinine clearance ≤30 mL/min 2
Pediatrics:
- 3 months to 12 years: 15 mg/kg twice daily (not to exceed 1 g/day) 1, 2
- ≥13 years: 1 g/day 1, 2
- Not recommended for infants <3 months (no data available) 2
- Not recommended for pediatric meningitis (insufficient CSF penetration) 2
Important Clinical Caveats
Carbapenems should be used judiciously to preserve their activity, as carbapenem resistance (particularly KPC-producing organisms) has become a critical issue worldwide 1. The use of ertapenem is particularly appropriate when:
- Treating community-acquired infections with suspected ESBL-producing organisms 1
- Outpatient parenteral antimicrobial therapy is needed (due to once-daily dosing) 3, 4
- Pseudomonas and Enterococcus coverage is not required 1
Ertapenem should NOT be used when Pseudomonas aeruginosa or Enterococcus species are suspected pathogens, as it lacks reliable activity against these organisms 1, 4. In such cases, Group 2 carbapenems (meropenem, imipenem) or alternative agents should be selected 1.