Chemical Properties
Imipenem (N-formimidoylthienamycin monohydrate) is a crystalline derivative of thienamycin, which is produced by Streptomyces cattleya. Its chemical name is (5 R,6S)-3-[[2-(formimidoylamino)ethyl]thio]-6-[( R)-1-hydroxyethyl ]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monohydrate. It is an off-white, nonhygroscopic crystalline compound with a molecular weight of 317.37. It is sparingly soluble in water and slightly soluble in methanol.
Discovery
Imipenem is an intravenous β-lactam antibiotic discovered by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Imipenem was patented in 1975 and approved for medical use in 1985.
Imipenem has a broad spectrum of activity against aerobic and anaerobic, Gram-positive and Gram-negative bacteria. It is particularly important for its activity against Pseudomonas aeruginosa and the Enterococcus species. It is not active against MRSA, however.
Broad-spectrum antibiotic
Imipenem is a semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains.It is stable to many beta-lactamases. Similar compounds include meropenem, known for having greater activity against Gram negative bacteria, and the newer ertapenem which exhibits a longer half-life due to increased binding to plasma proteins.
Imipenem acts as an antimicrobial through the inhibition of cell wall synthesis of various gram-positive and gram-negative bacteria.This inhibition of cell wall synthesis in gram-negative bateria is attained by binding to penicillin-binding proteins (PBPs).
Chemical Properties
Off-White Solid
Uses
Imipenem has a broad spectrum of antimicrobial action, which includes most clinically
significant microorganisms: Gram-positive, Gram-negative, aerobic, and anaerobic. It is
resistant with respect to most beta-lactamases of Gram-positive and Gram-negative bacteria. It is used for bacterial infections of the lower respiratory tract, infections of the urinary
and sexual tracts, infections of bones, joints, skin, soft tissues, intraabdominal and gynecological infections, bacterial septicemia, and endocarditis.
Imipenem undergoes enzymatic inactivation in the kidneys. In order to avoid this problem,
it is used in a 1:1 ratio in combination with cilastatin—the sodium salt of [R-[R,S-(Z)]]-7-[(2-
amino-2-carboxyethyl)thio]-2-[[(2,2-dimethylcyclopropyl)aminocarbonyl-2-heptenoic acid
(32.1.3.6), which inhibits metabolisms of imipenem in the kidneys. This combination of two
compounds is also used in medicine under the name primaxin.
Uses
An extremely broad-spectrum semi-synthetic antibiotic
Definition
ChEBI: Imipenem hydrate is a member of carbapenems. It contains an imipenem.
General Description
Chemical structure: -lactam
Biochem/physiol Actions
Imipenem is found effective against gram positive and negative aerobes and anaerobes. Imipenem is often combined with cilastatin, to inhibit its metabolism in kidney.
Synthesis
Imipenem, [5R-[5|á,6|á(R)]]-6-(1-hydroxyethyl)-3-[[2-[(iminomethyl)amino]
ethyl]thio]-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid (32.1.3.1), is the only carbapenem presently used in clinics. It is synthesized from thienamycin isolated from
Streptomyces cattleya by reacting it with the methyl formimidate.
Unlike penicillins and cephalosporins, which have a side aminoacyl group joined to the betalactam ring, imipenem has a |á-hydroxyethyl side chain. Significant resistance to hydrolysis
by beta-lactamases is observed in this compound, evidently thanks to the trans-configuration
of the side chain, while the side chain of penicillins and cephalosporins have a cis configuration.
