Ertapenem

Overview

Ertapenem (Invanz®) is a parenteral carbapenem antibiotic used in human medicine for serious bacterial infections caused by susceptible organisms. It is considered a critically important antimicrobial and is rarely used in veterinary medicine because of antimicrobial stewardship concerns and the limited clinical data available in dogs and cats.

In small animal practice, ertapenem should be regarded as an investigational option and reserved only for confirmed multidrug-resistant infections when culture and susceptibility testing show resistance to lower-tier alternatives. Empirical use is strongly discouraged, and consultation with a veterinary infectious disease specialist is recommended before treatment is initiated.

Mechanism of Action (MOA): Ertapenem is a beta-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins, resulting in disruption of cell wall formation and bacterial death. It is generally bactericidal and exhibits time-dependent antimicrobial activity.

Compared with other carbapenems, ertapenem has broad activity against many gram-positive, gram-negative, and anaerobic bacteria, but it has poor activity against Pseudomonas aeruginosa and Acinetobacter spp. Because of this narrower spectrum and the greater veterinary experience with other carbapenems, alternatives such as meropenem or imipenem are often preferred when a carbapenem is required.

Indications

Ertapenem should be reserved for dogs and cats with confirmed multidrug-resistant bacterial infections when culture and susceptibility testing demonstrate resistance to safer or lower-tier antimicrobial options. Because of its critical importance in human medicine, routine or empirical use is not appropriate.

• Resistant gram-negative infections: May be considered for serious infections caused by susceptible Enterobacteriaceae or other resistant gram-negative organisms when lower-tier therapy is unsuitable; examples include Escherichia coli and Klebsiella pneumoniae, but ertapenem is not useful against Pseudomonas aeruginosa.
• Mixed aerobic-anaerobic infections: May be useful where susceptible gram-negative organisms and anaerobic bacteria are both suspected or confirmed in a polymicrobial infection, provided Pseudomonas is not considered a likely pathogen.
• Patients unable to receive aminoglycosides: Can be considered where aminoglycoside therapy would be risky – for example in renal failure – or ineffective, as with resistant organisms or an infection in the central nervous system.
• Deep tissue or complicated infections: Reserve ertapenem for cases where culture and susceptibility confirm an ertapenem-susceptible multidrug-resistant organism, no suitable lower-tier option remains, and specialist consultation supports treatment.
• When other carbapenems are unavailable: If a carbapenem is required, meropenem or imipenem is preferred; consider ertapenem where an infectious disease expert has concluded that it is a viable and reasonable treatment.

• Regulatory status: No carbapenem is FDA-approved for use in animals, and no veterinary-labelled ertapenem product is listed; use in dogs and cats is extra-label.

Dosage (Reference)

Dog

Published veterinary dosing information for dogs is extremely limited. Reported use is anecdotal and should be considered extra-label. Because ertapenem is a critically important antimicrobial, treatment should only proceed when culture and susceptibility results support its use and no reasonable lower-tier alternatives remain.

Cat

Specific feline dosing studies are not available. The same anecdotal extra-label regimen reported for dogs and cats has been referenced clinically, but use in cats should remain highly selective and guided by confirmed susceptibility testing.

Warnings & Precautions

Ertapenem should be used with caution in dogs and cats because veterinary clinical experience is limited and published safety data are sparse. As a critically important antimicrobial, its use requires careful case selection, culture confirmation, and close monitoring throughout therapy.

• Restricted antimicrobial use: Reserve for confirmed multidrug-resistant infections when lower-tier antimicrobials are ineffective or inappropriate. Routine or empirical use is strongly discouraged.
• Hypersensitivity reactions: Contraindicated in patients with hypersensitivity to ertapenem or another carbapenem, and in patients that have had anaphylaxis after receiving a beta-lactam. In people, serious and occasionally fatal beta-lactam anaphylaxis has been reported.
• Cross-reactivity with beta-lactams: Cross-reactivity between penicillins and carbapenems appears low, but previous anaphylaxis after any beta-lactam remains a contraindication.
• Limited veterinary data: Canine pharmacokinetic figures have been published and differ sharply from the human ones – about 46% protein binding and a half-life near 1.3 hours, against roughly 90 to 95% binding and about 4 hours in people – while no feline data exist and dosing protocols have not been tested in either species.
• Neurologic effects: Carbapenems may lower the seizure threshold; use cautiously in patients with seizure disorders, CNS disease or conditions predisposing to neurotoxicity. High doses are associated with tremors and seizures, and rapid intravenous injection may itself provoke seizure activity.
• Renal dysfunction: Carbapenems are eliminated renally, and renal disease can prolong ertapenem elimination and may require dosage adjustment; monitor renal and neurologic status closely.
• Gastrointestinal effects: In people, diarrhoea is among the most common adverse effects; nausea and vomiting have occasionally been reported, and decreased appetite is also reported. Persistent gastrointestinal signs should prompt reassessment of therapy.
• Injection site discomfort: IV or SC administration may cause local irritation, pain, or inflammation. Proper dilution and administration technique are important.
• Pregnancy and nursing: Safety in pregnant or lactating dogs and cats has not been established. Use only when the expected maternal benefit outweighs the potential risk to the offspring. Ertapenem crosses the placenta in rats without reported teratogenic effects; it is present in human milk, but its effects on nursing animal offspring have not been established.
• Hospital stewardship protocols: Before a highest-priority antimicrobial is used, all of the following should hold: culture and susceptibility support the choice, no other reasonable alternative exists or the alternatives are contraindicated, the infection is not improving on current management, there is a good chance treatment will be curative, and a specialist in infectious disease, microbiology or infectious-disease pharmacology has been consulted.
• Not reliable for certain pathogens: Ertapenem has poor activity against Pseudomonas spp and Acinetobacter spp, so it should not be selected when these organisms are suspected or confirmed.
• Nephrotoxicity: Organ toxicity from beta-lactams is rare in animals, but nephrotoxicity is described as a risk of carbapenem treatment as a class, so renal values deserve monitoring in their own right and not only as a marker of drug exposure.
• Clostridioides difficile-associated diarrhoea: In people this has been reported with ertapenem and may range from mild diarrhoea to fatal colitis; consider it when diarrhoea follows antibacterial treatment.
• Intramuscular use and local anaesthetic sensitivity: The human product is reconstituted with 1% lidocaine for intramuscular injection, and on that route it is contraindicated in patients sensitive to lidocaine or other amide-type local anaesthetics. In dogs and cats ertapenem is given intravenously or subcutaneously only.
• Public health and the client conversation: Carbapenem-producing bacteria have been transmitted between people and their pets, and resistant organisms move in both directions between animals and humans. The ethical question raised by using a drug that is critically important in human medicine should be discussed with the owner before treatment begins.

Drug Interactions

Published veterinary interaction data for ertapenem are limited. Most clinically relevant concerns are based on human data, carbapenem class effects, or theoretical interactions. Concurrent medications should be reviewed carefully, especially in critically ill dogs and cats receiving multiple therapies.

• Probenecid: Renal elimination of ertapenem is reduced; in people this raises exposure by about 25% and lengthens the half-life by about 20%. Concurrent use is generally not recommended for dose extension purposes.
• Other beta-lactam antibiotics: Do not co-infuse ertapenem with other medications.
• Nephrotoxic medications: Carbapenem treatment carries a nephrotoxicity risk; monitor renal function closely.
• Seizure-threshold lowering drugs: In people, carbapenems including ertapenem can lower valproic acid or divalproex concentrations below the therapeutic range and permit breakthrough seizures; raising the valproate dose may not overcome it, and an antibacterial from another class should be considered where seizures are well controlled on valproate.
• Broad-spectrum antimicrobials: Antibacterial treatment alters the normal flora of the colon and can lead to overgrowth of Clostridioides difficile.
• Anticoagulant or intensive care medications: For patients receiving complex critical-care regimens, review all concurrent medicines and carry out additional monitoring where appropriate.
• Bacteriostatic antibiotics: Do not mix ertapenem with another antibiotic in the same vial or syringe.

• Intravenous fluids and co-infusion: Do not reconstitute or dilute ertapenem in a dextrose-containing fluid, and do not co-infuse it with other medicines. It is compatible with lactated Ringer’s solution, and has been reported compatible at a Y-site with 6% hetastarch in 0.9% sodium chloride; for anything else, check with a pharmacy reference.

Side Effects & Overdose

Side Effects

The adverse effect profile of ertapenem in dogs and cats is unknown, and in the carbapenem class adverse effects are described as rare. Reported expectations are largely extrapolated from human experience and from effects seen with other carbapenem antibiotics.

• Injection site reactions: Pain, swelling, irritation, or discomfort may occur after IV or SC administration.
• Diarrhea: One of the more likely gastrointestinal adverse effects associated with therapy.
• Nausea or vomiting: Gastrointestinal upset may occur during treatment, especially in sensitive patients.
• Reduced appetite: Decreased appetite is among the adverse experiences reported in people receiving ertapenem.
• Hypersensitivity reactions: Reactions including anaphylaxis may occur.
• Neurologic effects: Central nervous system effects have been reported in people: hallucinations, agitation and seizures rarely, and, in post-approval reports, tremor, myoclonus, abnormal coordination and altered mental status. High doses of a carbapenem carry a risk of seizures and tremors, and in adults treated with ertapenem seizures occurred in about 0.5% of patients.
• Tachycardia: Occasionally reported in people receiving ertapenem.
• Altered laboratory values: During prolonged treatment in people, periodic hepatic, haematopoietic and renal function testing is suggested. No specific laboratory assay interactions are noted.

Overdose

Significant overdose data in dogs and cats are unavailable. Clinical signs after an overdose are considered unlikely. The only figures reported are from people: 2 g given over 30 minutes or 3 g over one to two hours increased the incidence of nausea, and three 1 g doses given within 24 hours produced diarrhoea and transient dizziness in one patient.

• Gastrointestinal signs: In people, nausea and diarrhoea are the gastrointestinal signs reported after high or inadvertent dosing.
• Neurologic toxicity: High doses may increase the risk of central nervous system toxicity; the effects named are seizures and tremors.
• Injection-related complications: Pain or tissue irritation may occur if concentrated or excessive volumes are administered.
• Management: No specific antidote exists; treatment is supportive and based on clinical signs.
• Supportive care: Provide supportive treatment based on clinical signs and monitor for gastrointestinal, neurologic and renal complications.
• Reevaluation: Immediate veterinary assessment is recommended whenever a significant overdose is suspected, and consulting a 24-hour poison control service that provides veterinary-specific information is advised.

Key Notes

Practical clinical points that may help optimize the responsible and effective use of ertapenem in dogs and cats:

• Time-dependent killing: Clinical success depends on keeping drug concentrations above the organism’s MIC for an adequate part of the dosing interval, which makes schedule adherence important. That matters more here than in people: the reported canine half-life is about 1.3 hours with 46% protein binding, against roughly 4 hours and 90 to 95% binding in humans, so the human justification for infrequent dosing does not apply to the dog.
• Culture-driven de-escalation: Once updated culture results are available, transition to a narrower antimicrobial whenever possible.
• Hidden resistance mechanisms: Ertapenem is stable against many beta-lactamases, including extended-spectrum beta-lactamases, but carbapenemase-producing Klebsiella pneumoniae may resist the class. Methicillin-resistant Staphylococcus species and Enterococcus faecium are resistant to ertapenem. In methicillin-resistant staphylococci, mecA encodes PBP-2a with low affinity for beta-lactams.
• Site penetration matters: Carbapenems as a class enter the central nervous system when the meninges are inflamed, but a second antibacterial that continues to cross the blood-brain barrier as inflammation resolves may be needed.
• Source control remains essential: A highest-priority antimicrobial should not substitute for appropriate current management, including topical therapy, wound debridement and bandaging where those are indicated.
• Repeat cultures in non-responders: Reevaluate the patient about 72 hours after starting therapy, and confirm effective treatment with repeated bacterial culture and cytology during therapy and after it ends.
• Home administration planning: Cases managed outside the hospital require owners who are comfortable with sterile handling, storage, and injection technique.
• Record stewardship decisions: Document the rationale for use, the culture findings, the duration plan and the reassessment milestones whenever this drug is selected. The published criteria are worth recording against individually, including the requirement that these drugs should not be used in animals likely to have recurrent infections.
• Interpreting the culture report: No veterinary breakpoint exists for ertapenem. The human CLSI breakpoint for susceptible organisms is 4 micrograms/mL, most bacteria have an MIC below 2 micrograms/mL, and susceptibility to imipenem can be used as a marker for ertapenem where the laboratory does not test it directly.
• Storage and in-use stability: Keep unopened vials at or below 25°C (77°F) and protected from light. Once reconstituted and diluted in 0.9% sodium chloride, the solution is stable for 6 hours at room temperature, or 24 hours refrigerated and used within 4 hours of coming out of the refrigerator. Do not freeze it.
• Colour after reconstitution: A slight yellow tint after reconstitution is normal and does not affect potency, but a darker amber or brown colour suggests oxidation and loss of potency, and that vial should not be used.
• Available presentation: A single-dose vial of lyophilized powder for injection containing 1 g ertapenem (as 1.045 g ertapenem sodium), supplied as Invanz® and as generics, prescription only. There is no veterinary-labelled product and no oral, ophthalmic or ready-to-use liquid presentation.
• Vial composition: Each 1 g vial contains approximately 6 mEq of sodium and 175 mg of sodium bicarbonate as an excipient.
• No cilastatin required: Unlike imipenem, ertapenem resists renal dehydropeptidase I, so it needs no cilastatin and is supplied and given on its own.
• Preferred alternatives: If a carbapenem is genuinely required, meropenem or imipenem is preferred: both have more published veterinary use, and meropenem covers Pseudomonas aeruginosa and Acinetobacter, which ertapenem does not.