Ertapenem

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Ertapenem
Ertapenem Formula V.1.svg
Systematic (IUPAC) name
(4R,5S,6S)-3-[(3S,5S)-5-[(3-carboxyphenyl)carbamoyl]
pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-
oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
Clinical data
Trade names Invanz
AHFS/Drugs.com monograph
Pregnancy cat. B3 (AU) B (US)
Legal status Prescription only
Routes Intramuscular, intravenous
Pharmacokinetic data
Bioavailability 90% (intramuscular)
Protein binding Inversely proportional to concentration; 85 to 95%
Metabolism Minor hydrolysis of beta-lactam ring, CYP not involved
Half-life 4 hours
Excretion Renal (80%) and fecal (10%)
Identifiers
CAS number 153832-46-3 YesY
ATC code J01DH03
PubChem CID 150610
DrugBank DB00303
ChemSpider 132758 YesY
UNII G32F6EID2H YesY
KEGG D04049 N
ChEBI CHEBI:404903 YesY
ChEMBL CHEMBL1359 YesY
Chemical data
Formula C22H25N3O7S 
Mol. mass 475.516 g/mol
 N (what is this?)  (verify)

Ertapenem is a carbapenem antibiotic marketed by Merck as Invanz. It is structurally very similar to meropenem in that it possesses a 1-β-methyl group.

Indications[edit]

Ertapenem has been designed to be effective against Gram-negative and Gram-positive bacteria. 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.

Dosage[edit]

Ertapenem is dosed as 1 g given by intravenous injection over 30 minutes, or 1 g diluted with 3.2 ml of 1% lidocaine 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.

Pharmacokinetics[edit]

Unlike imipenem and meropenem, ertapenem is highly protein-bound, which results in a longer half-life (4 hours).[citation needed]

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, 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[edit]

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-lactamase are innately immune to ertapenem (as well as all carbapenems).[citation needed]

Side-effects[edit]

There are a few adverse effects of ertapenem like confusion and headache, which may worsen to convulsions and seizures. 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 became 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.[1]

As with many antibiotics, Clostridium difficile colitis has been associated with its use.

References[edit]

  1. ^ Livermore DM, Mushtaq S, Warner M (2005). "Selectivity of ertapenem for Pseudomonas aeruginosa mutants cross-resistant to other carbapenems". J Antimicrob Chemother 55 (3): 306–311. doi:10.1093/jac/dki009. PMID 15705643.