Imipenem (trade name Primaxin among others) is an

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

β-lactam

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

discovered by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Carbapenems are highly resistant to the β-lactamase enzymes produced by many multiple drug-resistant Gram-negative bacteria, thus play a key role in the treatment of infections not readily treated with other antibiotics. Imipenem was patented in 1975 and approved for medical use in 1985. It was discovered via a lengthy trial-and-error search for a more stable version of the natural product thienamycin, which is produced by the bacterium ''

Streptomyces cattleya ''Streptomyces cattleya'' is a Gram-positive bacterium which makes cephamycin, penicillin and thienamycin. The bacterium expresses a fluorinase enzyme, and the organism has been used to understand the biosynthesis of fluoroacetate and the antibac ...

''. Thienamycin has antibacterial activity, but is unstable in aqueous solution, so impractical to administer to patients. 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.

Medical uses

Spectrum of bacterial susceptibility and resistance

''Acinetobacter anitratus'', '' Acinetobacter calcoaceticus'', ''Actinomyces odontolyticus'', '' Aeromonas hydrophila'', ''Bacteroides distasonis'', ''Bacteroides uniformis'', and '' Clostridium perfringens'' are generally susceptible to imipenem, while '' Acinetobacter baumannii, some Acinetobacter'' spp., '' Bacteroides fragilis'', and '' Enterococcus faecalis'' have developed resistance to imipenem to varying degrees. Not many species are resistant to imipenem except '' Pseudomonas aeruginosa'' (Oman) and ''

Stenotrophomonas maltophilia ''Stenotrophomonas maltophilia'' is an aerobic, nonfermentative, Gram-negative bacterium. It is an uncommon bacterium and human infection is difficult to treat. Initially classified as ''Bacterium bookeri'', then renamed ''Pseudomonas maltophil ...

''.

Coadministration with cilastatin

Imipenem is rapidly degraded by the renal enzyme

dehydropeptidase Dipeptidases are enzymes secreted by enterocytes into the small intestine. Dipeptidases hydrolyze bound pairs of amino acids, called dipeptides. Dipeptidases are secreted onto the brush border of the villi in the small intestine, where they cleave ...

1 when administered alone, and is almost always coadministered with

cilastatin Cilastatin inhibits the human enzyme dehydropeptidase. Uses Dehydropeptidase is an enzyme found in the kidney and is responsible for degrading the antibiotic imipenem. Cilastatin can therefore be combined intravenously with imipenem in order to ...

to prevent this inactivation.

Adverse effects

Common adverse drug reactions are nausea and vomiting. People who are allergic to

penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...

and other β-lactam antibiotics should take caution if taking imipenem, as cross-reactivity rates are high. At high doses, imipenem is seizurogenic.

Mechanism of action

Imipenem acts as an antimicrobial through inhibiting cell wall synthesis of various Gram-positive and Gram-negative bacteria. It remains very stable in the presence of β-lactamase (both penicillinase and cephalosporinase) produced by some bacteria, and is a strong inhibitor of β-lactamases from some Gram-negative bacteria that are resistant to most β-lactam antibiotics.

References

External links

* {{Portal bar , Medicine Carbapenem antibiotics Enantiopure drugs Merck & Co. brands GABAA receptor negative allosteric modulators