Ertapenem

Ertapenem is a broad-spectrum carbapenem antibiotic used to treat selected moderate to severe bacterial infections caused by susceptible organisms. It belongs to the beta-lactam antibiotic class and works by binding to penicillin-binding proteins involved in bacterial cell-wall synthesis. This disrupts formation of the bacterial cell wall and ultimately causes bacterial cell death. Ertapenem has activity against a range of Gram-positive and Gram-negative bacteria as well as many anaerobic organisms, although it does not provide reliable activity against certain organisms including Pseudomonas aeruginosa, Acinetobacter species, Enterococcus species, and methicillin-resistant staphylococci. Ertapenem is administered parenterally, either by intravenous infusion or, in appropriate situations, by intramuscular injection. Its relatively long duration of activity permits once-daily dosing in adults and older children. It is used for infections including complicated intra-abdominal infections, community-acquired pneumonia, complicated skin and skin-structure infections including diabetic foot infections without osteomyelitis, complicated urinary tract infections, and acute pelvic infections under applicable regulatory indications. It is also used for surgical-site infection prophylaxis in adults undergoing elective colorectal surgery.

Ertapenem was developed as a carbapenem antibacterial with a pharmacokinetic profile supporting once-daily administration. The U.S. Food and Drug Administration granted the initial U.S. approval of INVANZ in 2001. The European Medicines Agency issued marketing authorization for Invanz on 18 April 2002, with subsequent product information updates. Ertapenem SUN, a generic version, received EU marketing authorization on 15 July 2022. Clinical development included randomized comparative studies evaluating ertapenem in intra-abdominal infections, community-acquired pneumonia, acute pelvic or gynaecological infections, skin and skin-structure infections, and other approved infection settings. The development program established once-daily ertapenem as an effective parenteral treatment option for susceptible bacterial infections.

Ertapenem is used for susceptible bacterial infections requiring parenteral treatment. U.S. indications include complicated intra-abdominal infections, complicated skin and skin-structure infections including diabetic foot infections without osteomyelitis, community-acquired pneumonia, complicated urinary tract infections including pyelonephritis, and acute pelvic infections. It is also indicated in adults for prevention of surgical-site infection following elective colorectal surgery. European indications include intra-abdominal infections, community-acquired pneumonia, acute gynaecological infections, and diabetic foot infections of the skin and soft tissue, together with colorectal surgical prophylaxis in adults. Appropriate antimicrobial selection should take into account local susceptibility patterns and official antimicrobial stewardship guidance.

Ertapenem may be administered intravenously or intramuscularly. For adults and patients aged 13 years and older, the usual treatment dose is 1 g once daily. For children from 3 months through 12 years of age, the recommended dose is 15 mg/kg twice daily, without exceeding 1 g per day. Intravenous administration is generally given by infusion over approximately 30 minutes. Treatment duration depends on the type and severity of infection and clinical response, with many treatment courses lasting approximately 3 to 14 days. For prevention of surgical-site infection after elective colorectal surgery, adults receive a single 1 g dose within one hour before surgery. Dose adjustment is required in adults with advanced renal impairment, and additional considerations apply to patients receiving haemodialysis. Ertapenem should not be mixed or co-infused with other medications and should not be prepared using dextrose-containing diluents.

Common adverse effects of ertapenem include diarrhea, nausea, vomiting, headache, infusion-site or injection-site reactions, abdominal discomfort, and changes in liver enzymes. In children, diarrhea, vomiting, fever, and infusion-site complications may occur. Mild skin reactions and other gastrointestinal symptoms can also be reported. The frequency and severity of adverse effects vary between patients and may depend on the underlying infection, age, renal function, and concurrent medicines. Patients should report persistent diarrhea, significant rash, worsening injection-site symptoms, or other troublesome reactions so that the treating healthcare professional can determine appropriate management.

Important risks associated with ertapenem include serious hypersensitivity reactions, seizures, Clostridioides difficile-associated diarrhea, severe skin reactions, and other serious infections or complications. Patients with a history of serious beta-lactam hypersensitivity require particular caution because cross-reactive allergic reactions can occur within the beta-lactam class. Seizures and other central nervous system adverse effects have been reported, with increased concern in patients with underlying neurological disorders or impaired renal function. Antibiotic-associated diarrhea can occur during or after treatment and may require medical evaluation. Treatment should be discontinued or modified when clinically significant hypersensitivity or other serious adverse reactions occur. Ertapenem should be used only when bacterial infection is proven or strongly suspected and according to appropriate antimicrobial stewardship principles.

Before treatment, clinicians should assess the suspected infection, previous antimicrobial exposure, allergy history, renal function, neurological history, and concomitant medicines. Renal impairment is particularly important because ertapenem is substantially eliminated through the kidneys and dose adjustment may be necessary. Ertapenem can interact with valproic acid and related medicines by reducing valproate concentrations, potentially increasing the risk of breakthrough seizures; concomitant use should generally be avoided when possible. Probenecid can affect ertapenem clearance and is not generally recommended as a means of extending ertapenem exposure. As with other broad-spectrum antibiotics, unnecessary use can contribute to antimicrobial resistance and disruption of normal intestinal flora. Appropriate microbiological testing and antimicrobial stewardship should therefore guide treatment whenever practical.

Prescribers should confirm that the suspected or identified pathogen is likely to be susceptible to ertapenem and select therapy according to infection site, severity, local resistance patterns, and antimicrobial stewardship principles. Renal function should be assessed before treatment and monitored when clinically appropriate, particularly in older adults and patients with renal impairment. Review the patient's history of serious reactions to penicillins, cephalosporins, carbapenems, or other beta-lactam antibiotics. Particular attention should be given to patients taking valproic acid or related anticonvulsants because ertapenem can reduce valproate exposure. Pharmacists should verify the preparation and administration method, ensure appropriate dilution and infusion procedures, and review renal dosing. During therapy, monitor clinical response, gastrointestinal symptoms, hypersensitivity reactions, neurological symptoms, and injection or infusion-site reactions.