|Trade names||Invanz, others|
|Main uses||Pneumonia, diabetic foot infection, intra-abdominal infection|
|Side effects||Diarrhea, nausea, headache, rash, pain at the site of delivery|
|Protein binding||Inversely proportional to concentration; 85 to 95%|
|Metabolism||Hydrolysis of beta-lactam ring, CYP not involved|
|Elimination half-life||4 hours|
|Excretion||Kidney (80%) and fecal (10%)|
|Chemical and physical data|
|Molar mass||475.52 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Ertapenem, sold under the brand name Invanz among others, is an antibiotic used for the treatment of infections in the abdomen, pneumonia, upper female reproductive system, urinary tract, and diabetic foot. It is given by injection into a vein or muscle.
Common side effects include diarrhea, nausea, headache, rash, and pain at the site of delivery. Other side effects may include Clostridium difficile-associated colitis, seizures, and allergic reactions including anaphylaxis. Use during pregnancy and breastfeeding appears to be safe, but has not been well studied. It is in the carbapenem family of medications, which usually results in the death of the bacteria.
Ertapenem was approved for medical use in the United States in 2001 and Europe in 2002. It is avaliable as a generic medication. In the United Kingdom it costs the NHS about £32 per dose. In the United States it costs about 34 USD per dose as of 2021.
Ertapenem is used for the treatment of intra-abdominal infections, community-acquired pneumonia, pelvic infections, and diabetic foot infections, with bacteria that are susceptible to this drug, or expected to be so. It can also be used to prevent infections after colorectal surgery. In the United States it is also indicated for the treatment of complicated urinary tract infections including pyelonephritis.
It is used at a dose of 1 gram once per day.
The drug is contraindicated in people with known hypersensitivity to ertapenem or other carbapenem type antibiotics, or with severe hypersensitivity reactions (such as anaphylaxis or severe skin reactions) to other beta-lactam antibiotics in the past.
Common side effects are diarrhoea (in 5% of people receiving ertapenem), nausea (in 3%) and vomiting, reactions at the injection site (5%, including pain and inflammation of the vein), and headache. Uncommon but possibly serious side effects include candida infections, seizures, skin reactions such as rashes (including nappy rash in children), and anaphylaxis. Hypersensitivity cross-reactions with penicillins are rare.
Ertapenem can reduce the concentrations of valproic acid, an epilepsy medication, by 70% and perhaps up to 95% within 24 hours; this can result in inadequate control of seizures. The effect is described for other carbapenem antibiotics as well, but seems to be most pronounced for ertapenem and meropenem. This is likely caused by several mechanisms: carbapenems inhibit transport of valproic acid from the gut into the body; they may increase metabolization of valproic acid to its glucuronide; they may reduce enterohepatic circulation and recycling of valproic acid glucuronide by acting against gut bacteria; and they may block transporter proteins that pump valproic acid out of red blood cells into the blood plasma. The effect is also seen in reverse: in cases where ertapenem has been withdrawn blood concentrations of valproate have been reported to rise.
Mechanism of action
Like all beta-lactam antibiotics, ertapenem is bactericidal. It inhibits cross-linking of the peptidoglycan layer of bacterial cell walls by blocking a type of enzymes called penicillin-binding proteins (PBPs). When a bacterial cell tries to synthesize new cell wall in order to grow and divide, the attempt fails, rendering the cell vulnerable to osmotic disruption. Additionally, the surplus of peptidoglycan precursors triggers autolytic enzymes of the bacterium, which disintegrate the existing wall.
Bacteria that are normally susceptible to ertapenem treatment (at least in Europe) include:
- Gram-positive aerobes
- Gram-negative aerobes
- The US Food and Drug Administration (FDA) label specifies activity against additional anaerobes:
Bacteria that show no clinically relevant response to ertapenem include methicillin-resistant Staphylococcus species (including MRSA) as well as Acinetobacter, Aeromonas, Enterococcus, and Pseudomonas.
Microorganisms can become resistant to ertapenem by producing carbapenemases, enzymes that inactivate the drug by opening the beta-lactam ring. Other mechanisms of resistance against carbapenems are development of efflux pumps that transport the antibiotics out of the bacterial cells, mutations of PBPs, and mutations of Gram-negative bacteria's porins which are necessary for carbapenems to enter the bacteria.
The route of administration has only a slight effect on the drug's concentrations in the bloodstream: when given as an intramuscular injection, its bioavailability is 90% (as compared to the 100% availability when given directly into a vein), and its highest concentrations in the blood plasma are reached after about 2.3 hours. In the blood, 85–95% of ertapenem are bound to plasma proteins, mostly albumin. Plasma protein binding is higher for lower concentrations, and vice versa. The drug is only partially metabolized, with 94% circulating in form of the parent substance and 6% as metabolites. The main metabolite is the inactive hydrolysis product with the ring opened.
Ertapenem is mainly eliminated via the kidneys and urine (80%) and to a minor extent via the faeces (10%). Of the 80% found in the urine, 38% is excreted as the parent drug and 37% as the ring-opened metabolite. The biological half-life is about 3.5 hours in women, 4.2 hours in men and 2.5 hours in children up to 12 years of age.
Comparison with other antibiotics
Like all carbapenem antibiotics, ertapenem has a broader spectrum of activity than other beta-lactams like penicillins and cephalosporins. Similar to doripenem, meropenem and biapenem, ertapenem has slightly better activity against many Gram-negative bacteria than other carbapenems such as imipenem. In contrast to imipenem, doripenem and meropenem, it is not active against Enterococcus, Pseudomonas and Acinetobacter species.
For diabetic foot infections, ertapenem as a single treatment or in combination with vancomycin has been found to be more effective and have fewer side effects than tigecycline, but in severe cases it is less effective than piperacillin/tazobactam.
Regarding pharmacokinetics, imipenem, doripenem and meropenem have lower plasma protein bindings (up to 25%) and shorter half-lives (about one hour) than ertapenem.
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