Ertapenem
Encyclopedia
Ertapenem is a carbapenem
antibiotic
marketed by Merck
as Invanz. It is structurally very similar to meropenem
in that it possess a 1-β-methyl group.
. It is not active against MRSA, ampicillin
-resistant enterococci
, Pseudomonas aeruginosa
or Acinetobacter
species. Ertapenem also has clinically useful activity against anaerobic bacteria.
Ertapenem has been shown to be active against most isolates of the following micro-organisms in vitro and in clinical infections.
Aerobic and facultative gram-positive microorganisms:
Staphylococcus aureus (methicillin susceptible isolates only),
Streptococcus agalactiae,
Streptococcus pneumoniae (penicillin susceptible isolates only),
Streptococcus pyogenes,
Note: Methicillin-resistant staphylococci and Enterococcus spp. are resistant to ertapenem.
Aerobic and facultative gram-negative microorganisms:
Escherichia coli,
Haemophilus influenzae (Beta-lactamase negative isolates only),
Klebsiella pneumoniae,
Moraxella catarrhalis,
Proteus mirabilis,
Anaerobic microorganisms:
Bacteroides fragilis,
Bacteroides distasonis,
Bacteroides ovatus,
Bacteroides thetaiotaomicron,
Bacteroides uniformis,
Clostridium clostridioforme,
Eubacterium lentum,
Peptostreptococcus species,
Porphyromonas asaccharolytica,
Prevotella bivia,
Ertapenem is marketed by Merck as a first-line treatment for community-acquired infections. It should not be used as empirical treatment for hospital-acquired infections because of its lack of activity against Pseudomonas aeruginosa. In practice, it is reserved primarily for use against Extended spectrum beta-lactamase (ESBL)-producing and high level AmpC-producing Gram-negative bacteria.
given intramuscularly. There is no oral preparation of ertapenem available. Ertapenem cannot be mixed with glucose.
The marketing slogan
for ertapenem is "The Power of One", because the dose is one gram
, once a day.
and meropenem
, ertapenem is highly protein bound, which results in a longer half life (4 hours).
Ertapenem is excreted
primarily (80%) by the kidneys. Metabolism by the liver is not clinically important and does not affect dosing.
Patients on haemodialysis should be given ertapenem at least 6 hours before dialysis. If it is given less than six hours before dialysis, then the patient should be given an additional dose of 150 mg IV after dialysis. Ideally, patients on haemodialysis should be given ertapenem immediately following dialysis.
are innately immune to ertapenem (as well as all carbapenem
s).
s of ertapenem. The only absolute contra-indication is a previous anaphylactic reaction
to ertapenem or other β-lactam antibiotic. There are no studies done in pregnant women, so the manufacturers cannot comment on its safety in pregnancy. In 2006, Ertapenem is now approved for pediatric use in certain infections. Ertapenem is not recommended for children under 3 months of age and children with meningitis
.
Use of all antibiotics is associated with increased rates of resistance
(although carbapenem resistance is currently rare). There is particular worry that although ertapenem has no clinically useful activity against Pseudomonas aeruginosa
, widespread use of ertapenem could still lead to increased carbapenem resistance in Pseudomonas.
Like many antibiotics, Clostridium difficile
colitis
has been associated with its use.
Carbapenem
Carbapenems are a class of β-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to most β-lactamases...
antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
marketed by Merck
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
as Invanz. It is structurally very similar to meropenem
Meropenem
Meropenem is an ultra-broad spectrum injectable antibiotic used to treat a wide variety of infections, including meningitis and pneumonia. It is a beta-lactam and belongs to the subgroup of carbapenem, similar to imipenem and ertapenem. Meropenem was originally developed by Sumitomo Pharmaceuticals...
in that it possess a 1-β-methyl group.
Indications
Ertapenem has been designed to be effective against Gram negative and Gram positive bacteriaBacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
. It is not active against MRSA, ampicillin
Ampicillin
Ampicillin is a beta-lactam antibiotic that has been used extensively to treat bacterial infections since 1961. Until the introduction of ampicillin by the British company Beecham, penicillin therapies had only been effective against Gram-positive organisms such as staphylococci and streptococci...
-resistant enterococci
Enterococcus
Enterococcus is a genus of lactic acid bacteria of the phylum Firmicutes. Enterococci are Gram-positive cocci that often occur in pairs or short chains, and are difficult to distinguish from streptococci on physical characteristics alone. Two species are common commensal organisms in the...
, Pseudomonas aeruginosa
Pseudomonas aeruginosa
Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
or Acinetobacter
Acinetobacter
Acinetobacter [asz−in−ée−toe–back−ter] is a genus of Gram-negative bacteria belonging to the Gammaproteobacteria. Acinetobacter species are non-motile and oxidase-negative, and occur in pairs under magnification....
species. Ertapenem also has clinically useful activity against anaerobic bacteria.
Ertapenem has been shown to be active against most isolates of the following micro-organisms in vitro and in clinical infections.
Aerobic and facultative gram-positive microorganisms:
Staphylococcus aureus (methicillin susceptible isolates only),
Streptococcus agalactiae,
Streptococcus pneumoniae (penicillin susceptible isolates only),
Streptococcus pyogenes,
Note: Methicillin-resistant staphylococci and Enterococcus spp. are resistant to ertapenem.
Aerobic and facultative gram-negative microorganisms:
Escherichia coli,
Haemophilus influenzae (Beta-lactamase negative isolates only),
Klebsiella pneumoniae,
Moraxella catarrhalis,
Proteus mirabilis,
Anaerobic microorganisms:
Bacteroides fragilis,
Bacteroides distasonis,
Bacteroides ovatus,
Bacteroides thetaiotaomicron,
Bacteroides uniformis,
Clostridium clostridioforme,
Eubacterium lentum,
Peptostreptococcus species,
Porphyromonas asaccharolytica,
Prevotella bivia,
Ertapenem is marketed by Merck as a first-line treatment for community-acquired infections. It should not be used as empirical treatment for hospital-acquired infections because of its lack of activity against Pseudomonas aeruginosa. In practice, it is reserved primarily for use against Extended spectrum beta-lactamase (ESBL)-producing and high level AmpC-producing Gram-negative bacteria.
Dosage
Ertapenem is dosed as 1g given by intravenous injection over 30 minutes, or 1g diluted with 3.2ml of 1% lidocaineLidocaine
Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...
given intramuscularly. There is no oral preparation of ertapenem available. Ertapenem cannot be mixed with glucose.
The marketing slogan
Slogan
A slogan is a memorable motto or phrase used in a political, commercial, religious and other context as a repetitive expression of an idea or purpose. The word slogan is derived from slogorn which was an Anglicisation of the Scottish Gaelic sluagh-ghairm . Slogans vary from the written and the...
for ertapenem is "The Power of One", because the dose is one gram
Gram
The gram is a metric system unit of mass....
, once a day.
Pharmacokinetics
Unlike imipenemImipenem
Imipenem is an intravenous β-lactam antibiotic developed in 1980. It has an extremely broad spectrum of activity.Imipenem belongs to the subgroup of carbapenems. It is derived from a compound called thienamycin, which is produced by the bacterium Streptomyces cattleya...
and meropenem
Meropenem
Meropenem is an ultra-broad spectrum injectable antibiotic used to treat a wide variety of infections, including meningitis and pneumonia. It is a beta-lactam and belongs to the subgroup of carbapenem, similar to imipenem and ertapenem. Meropenem was originally developed by Sumitomo Pharmaceuticals...
, ertapenem is highly protein bound, which results in a longer half life (4 hours).
Ertapenem is excreted
Excretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...
primarily (80%) by the kidneys. Metabolism by the liver is not clinically important and does not affect dosing.
Patients on haemodialysis should be given ertapenem at least 6 hours before dialysis. If it is given less than six hours before dialysis, then the patient should be given an additional dose of 150 mg IV after dialysis. Ideally, patients on haemodialysis should be given ertapenem immediately following dialysis.
Resistance
Acquired resistance to ertapenem is usually mediated by up-regulation of efflux mechanisms and by the selection of porin-deficient mutants. Organisms that produce a metallo-β-lactamaseBeta-lactamase
Beta-lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotics like penicillins, cephamycins, and carbapenems . These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam...
are innately immune to ertapenem (as well as all carbapenem
Carbapenem
Carbapenems are a class of β-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to most β-lactamases...
s).
Side effects
There are few adverse effectAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s of ertapenem. The only absolute contra-indication is a previous anaphylactic reaction
Anaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
to ertapenem or other β-lactam antibiotic. There are no studies done in pregnant women, so the manufacturers cannot comment on its safety in pregnancy. In 2006, Ertapenem is now approved for pediatric use in certain infections. Ertapenem is not recommended for children under 3 months of age and children with meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
.
Use of all antibiotics is associated with increased rates of resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...
(although carbapenem resistance is currently rare). There is particular worry that although ertapenem has no clinically useful activity against Pseudomonas aeruginosa
Pseudomonas aeruginosa
Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
, widespread use of ertapenem could still lead to increased carbapenem resistance in Pseudomonas.
Like many antibiotics, Clostridium difficile
Clostridium difficile
Clostridium difficile , also known as "CDF/cdf", or "C...
colitis
Pseudomembranous colitis
Pseudomembranous colitis, a cause of antibiotic-associated diarrhea , is an infection of the colon. It is often, but not always, caused by the bacterium Clostridium difficile. Because of this, the informal name C. difficile colitis is also commonly used. The illness is characterized by...
has been associated with its use.