Ertapenem

Ertapenem belongs to the carbapenem family, a group of bactericidal antibiotics. It acts on the bacterial cell wall: it binds to the penicillin-binding proteins, known as PBPs, the enzymes that assemble that wall. By blocking these enzymes, it prevents the bacterium from building its envelope. Deprived of its wall, the bacterium dies.

In Escherichia coli, ertapenem binds strongly to PBPs 1a, 1b, 2, 3, 4 and 5, with a marked preference for PBPs 2 and 3. These two targets govern the shape and division of the bacterium. Blocking them disrupts the assembly of the wall, so that the bacterium can no longer divide or hold its structure together.

Ertapenem is reserved for moderate to severe bacterial infections. It treats complicated intra-abdominal infections and complicated skin and soft tissue infections, including diabetic foot without bone involvement. It also covers community-acquired pneumonia, complicated urinary tract infections including pyelonephritis, and acute pelvic infections.

It is also used to prevent surgical site infections following elective colorectal surgery in adults. In this indication, it is given around the time of the procedure to reduce the risk of wound infection. The choice of ertapenem depends on the suspected organism and the severity, a decision that rests with the physician.

Ertapenem is not taken by mouth. It is given parenterally: as an intravenous infusion over 30 minutes, or as an intramuscular injection. The question of taking it with or without food therefore does not arise, unlike with a tablet.

Its plasma half-life is around 4 hours in young adults, and 2.5 hours in children aged 3 months to 12 years, which usually allows a single administration per day. The drug is also highly bound to blood proteins, about 95 % at usual concentrations. The prescribed course is followed to the end, without stopping the treatment on one’s own as soon as one feels better.

In adults, the most frequent adverse effects reported in trials are diarrhea (10.3 %), an increase in ALT (8.8 %), nausea (8.5 %), an increase in AST (8.4 %), a complication of the infused vein (7.1 %), headache (5.6 %), altered mental status (5.1 %) and fever (5.0 %). In children, the most common are diarrhea (11.7 %), vomiting (10.2 %), pain at the infusion site (7.0 %) and fever (4.9 %).

Seizures and other effects on the central nervous system have been reported with ertapenem: in trials, seizures occurred in 0.5 % of patients. The risk increases in the presence of a central nervous system disorder, such as a brain lesion or a history of seizures, or of impaired kidney function. Like other antibiotics, ertapenem can also cause diarrhea related to Clostridioides difficile, sometimes severe.

Ertapenem targets the bacteria responsible for the infection, but along the way it affects part of the intestinal flora. Severe or prolonged diarrhea causes a loss of potassium and lowers blood potassium. Yet the body needs this mineral for the heart, muscle function and acid-base balance.

The intestinal flora renders another service: the bacteria in the lower part of the intestine produce a share of vitamin K, which is needed for blood clotting. When the antibiotic disrupts these bacteria, this internal production decreases. Dietary intake then takes over to cover the needs.

Two interactions call for attention. With valproic acid or divalproex, carbapenems, including ertapenem, lower the concentration of valproic acid, with a risk of seizures: this combination is generally advised against. With probenecid, the renal excretion of ertapenem decreases and its blood concentration rises, so that the combination is not recommended.

Monitoring focuses on the liver and the kidney. Elevations of transaminases, ALT and AST, are frequent, which warrants monitoring of liver function during treatment. The dose is adjusted according to kidney function, and the risk of seizures increases in cases of renal impairment, hence the value of monitoring the kidney as well.