Introduction
Ertapenem is a broad-spectrum carbapenem antibiotic belonging to the beta-lactam class of antimicrobial agents. It was approved by the FDA in 2001 and represents an important therapeutic option for treating moderate to severe infections caused by susceptible organisms. Ertapenem is distinguished from other carbapenems by its once-daily dosing regimen and narrower spectrum of activity against Gram-positive and anaerobic bacteria compared to imipenem or meropenem.
Mechanism of Action
Ertapenem exerts its bactericidal activity by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs). Like other beta-lactam antibiotics, ertapenem disrupts the cross-linking of peptidoglycan chains in the bacterial cell wall, leading to osmotic instability and cell lysis. It demonstrates high affinity for multiple PBPs, including PBP2 and PBP3, contributing to its broad-spectrum activity against both Gram-positive and Gram-negative organisms.
Indications
FDA-approved indications for ertapenem include:
- Complicated intra-abdominal infections
- Complicated skin and skin structure infections
- Community-acquired pneumonia
- Complicated urinary tract infections
- Acute pelvic infections including endometritis and pelvic inflammatory disease
- Prophylaxis of surgical site infection following elective colorectal surgery
Dosage and Administration
Standard adult dosing: 1 gram intravenously once daily Administration:- IV infusion over 30 minutes
- Not for intramuscular administration
- Reconstitute with appropriate diluent (water for injection, normal saline, or bacteriostatic water)
- Renal impairment:
- CrCl 30 mL/min/1.73m² or less: 500 mg once daily - Hemodialysis: 500 mg daily; administer after dialysis session
- Pediatric patients (3 months to 12 years): 15 mg/kg twice daily (maximum 1 g/day)
- Elderly: Consider renal function adjustments
Pharmacokinetics
Absorption: Administered exclusively intravenously; complete bioavailability Distribution: Widely distributed into body tissues and fluids; plasma protein binding approximately 85-95% Volume of distribution: Approximately 0.12 L/kg Metabolism: Undergoes minimal hepatic metabolism via hydrolysis of the beta-lactam ring Elimination: Primarily renal excretion (80% as unchanged drug); half-life approximately 4 hours Special considerations: Poor penetration into cerebrospinal fluid; not recommended for meningitisContraindications
- Known hypersensitivity to ertapenem, other carbapenems, or beta-lactam antibiotics
- Patients who have experienced anaphylactic reactions to beta-lactams
Warnings and Precautions
Boxed Warning: None Important precautions:- Seizures and other CNS adverse reactions have been reported
- Clostridium difficile-associated diarrhea may occur
- Development of drug-resistant bacteria possible with prolonged use
- Caution in patients with CNS disorders or renal impairment
- Cross-hypersensitivity with other beta-lactam antibiotics
- Thrombophlebitis at injection site may occur
- Prolonged use may result in fungal or bacterial superinfection
Drug Interactions
Significant interactions:- Probenecid: Concurrent administration increases ertapenem AUC by approximately 25% and prolongs half-life
- Valproic acid: Ertapenem may significantly reduce valproic acid levels, increasing seizure risk
- Other medications that compete for renal tubular secretion
Adverse Effects
Common (≥1%):- Diarrhea (5-10%)
- Infusion site reactions (3-9%)
- Nausea (3-7%)
- Headache (3-6%)
- Vomiting (2-4%)
- Seizures (0.5%)
- Pseudomembranous colitis
- Hypersensitivity reactions including anaphylaxis
- Eosinophilia
- Thrombocytopenia
- Elevated liver enzymes
- Stevens-Johnson syndrome
Monitoring Parameters
Baseline:- Complete blood count with differential
- Renal function tests
- Liver function tests
- Culture and sensitivity results
- Clinical response to treatment
- Signs of superinfection
- Diarrhea (assess for C. difficile)
- Seizure activity in susceptible patients
- Injection site reactions
- Periodic renal function in patients with pre-existing impairment
- Resolution of infection
- Development of late adverse effects
Patient Education
Important points to discuss:- Complete the full course of therapy even if feeling better
- Report any signs of allergic reaction immediately (rash, itching, swelling)
- Inform healthcare providers about all medications being taken
- Report severe diarrhea or abdominal pain during or after treatment
- Use caution when driving or operating machinery due to potential CNS effects
- Inform healthcare providers of history of seizures or kidney problems
- Discuss use of reliable contraception as antibiotic may reduce effectiveness of oral contraceptives
References
1. FDA Prescribing Information: INVANZ® (ertapenem sodium). 2021 2. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 52nd edition 3. Lexicomp Online. Ertapenem monograph. Wolters Kluwer Clinical Drug Information 4. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th edition 5. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing 6. Shah PM, Isaacs RD. Ertapenem, the first once-a-day carbapenem. Expert Opin Investig Drugs. 2002 7. Keating GM, Perry CM. Ertapenem: a review of its use in the treatment of bacterial infections. Drugs. 2005
This monograph is intended for educational purposes only and should not replace clinical judgment. Always consult appropriate references and guidelines for specific patient care decisions.