Imipenem (trade name Primaxin among others) is a synthetic 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 pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

belonging to the

carbapenem Carbapenems are a class of very effective antibiotic agents most commonly used for treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Si ...

s chemical class. developed by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Carbapenems are highly resistant to the

β-lactamase Beta-lactamases (β-lactamases) are enzymes () produced by bacteria that provide Multiple drug resistance, multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem ...

enzymes produced by many multiple drug-resistant Gram-negative bacteria, thus playing a key role in the treatment of infections not readily treated with other antibiotics. It is usually administered through

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 nutr ...

injection. Imipenem was patented in 1975 and approved for medical use in 1985. It was developed via a lengthy trial-and-error search for a more stable version of the natural product

thienamycin Thienamycin (also known as thienpenem) is one of the most potent naturally produced antibiotics known thus far, discovered in '' Streptomyces cattleya'' in 1976. Thienamycin has excellent activity against both Gram-positive and Gram-negative bact ...

, 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 fluoroacetic acid, fluoroacet ...

''. Thienamycin has antibacterial activity, but is unstable in aqueous solution, thus it is practically of no medicinal use. Imipenem has a broad spectrum of activity against

aerobic Aerobic means "requiring air," in which "air" usually means oxygen. Aerobic may also refer to * Aerobic exercise, prolonged exercise of moderate intensity * Aerobics, a form of aerobic exercise * Aerobic respiration, the aerobic process of cellu ...

and

anaerobic Anaerobic means "living, active, occurring, or existing in the absence of free oxygen", as opposed to aerobic which means "living, active, or occurring only in the presence of oxygen." Anaerobic may also refer to: *Adhesive#Anaerobic, Anaerobic ad ...

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain is ...

and

Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

. It is particularly important for its activity against ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...

'' and ''

Enterococcus ''Enterococcus'' is a large genus of lactic acid bacteria of the phylum Bacillota. Enterococci are Gram-positive cocci that often occur in pairs ( diplococci) or short chains, and are difficult to distinguish from streptococci on physical ch ...

'' species. However, it is not active against

MRSA Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...

Medical uses

Spectrum of bacterial susceptibility and resistance

''Acinetobacter anitratus'', ''

Acinetobacter calcoaceticus ''Acinetobacter calcoaceticus'' is a bacterial species of the genus '' Acinetobacter''. It is a nonmotile, Gram-negative coccobacillus. It grows under aerobic conditions, is catalase positive and oxidase negative. ''A. calcoaceticus'' is a part ...

'', ''Actinomyces odontolyticus'', ''

Aeromonas hydrophila ''Aeromonas hydrophila'' is a heterotrophic, Gram-negative, rod-shaped bacterium mainly found in areas with a warm climate. This bacterium can be found in fresh or brackish water. It can survive in aerobic and anaerobic environments, and can ...

'', ''Bacteroides distasonis'', ''Bacteroides uniformis'', and ''

Clostridium perfringens ''Clostridium perfringens'' (formerly known as ''C. welchii'', or ''Bacillus welchii'') is a Gram-positive, bacillus (rod-shaped), anaerobic, spore-forming pathogenic bacterium of the genus '' Clostridium''. ''C. perfringens'' is ever-present ...

'' are generally susceptible to imipenem, while ''

Acinetobacter baumannii ''Acinetobacter baumannii'' is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromis ...

, some

Acinetobacter ''Acinetobacter'' is a genus of Gram-negative bacteria belonging to the wider class of Gammaproteobacteria. ''Acinetobacter'' species are oxidase-negative, exhibit twitching motility, and occur in pairs under magnification. They are important ...

'' spp., ''

Bacteroides fragilis ''Bacteroides fragilis'' is an anaerobic, Gram-negative, pleomorphic to rod-shaped bacterium. It is part of the normal microbiota of the human colon and is generally commensal, but can cause infection if displaced into the bloodstream or surrou ...

'', and ''

Enterococcus faecalis ''Enterococcus faecalis'' – formerly classified as part of the group D '' Streptococcus,'' is a Gram-positive, commensal bacterium naturally inhabiting the gastrointestinal tracts of humans. Like other species in the genus '' Enterococcus'', ' ...

'' have developed resistance to imipenem to varying degrees. Not many species are resistant to imipenem except ''

'' (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 maltoph ...

''.

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 acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 ...

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 reaction An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or may result from the combination of two or more drugs. The meaning of this ...

s are nausea and vomiting. People who are allergic to

penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...

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 Drugs developed by Merck & Co. GABAA receptor negative allosteric modulators