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.
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.
