Chemistry:Imipenem

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Short description: Carbapenem antibiotic
Imipenem
Imipenem.svg
Imipenem ball-and-stick.png
Clinical data
Trade namesPrimaxin
AHFS/Drugs.comInternational Drug Names
MedlinePlusa686013
License data
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
Routes of
administration		IM, IV
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding20%
MetabolismRenal
Elimination half-life38 minutes (children), 60 minutes (adults)
ExcretionUrine (70%)
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
Chemical and physical data
FormulaC12H17N3O4S
Molar mass299.35 g·mol−1
3D model (JSmol)
  (verify)

Imipenem (trade name Primaxin among others) is a synthetic β-lactam antibiotic belonging to the carbapenems chemical class. developed by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s.[1] Carbapenems are highly resistant to the β-lactamase enzymes produced by many multiple drug-resistant Gram-negative bacteria,[2] thus playing a key role in the treatment of infections not readily treated with other antibiotics.[3] It is usually administered through intravenous injection.

Imipenem was patented in 1975 and approved for medical use in 1985.[4] It was developed 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. Thienamycin has antibacterial activity, but is unstable in aqueous solution, thus it is practically of no medicinal use.[5] Imipenem has a broad spectrum of activity against aerobic and anaerobic, Gram-positive and Gram-negative bacteria.[6] It is particularly important for its activity against Pseudomonas aeruginosa and Enterococcus species. However, it is not active against MRSA.

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.[7]

Coadministration with cilastatin

Imipenem is rapidly degraded by the renal enzyme dehydropeptidase 1 when administered alone, and is almost always coadministered with cilastatin to prevent this inactivation.[8]

Adverse effects

Common adverse drug reactions are nausea and vomiting. People who are allergic to penicillin and other β-lactam antibiotics should take caution if taking imipenem, as cross-reactivity rates are high. At high doses, imipenem is seizurogenic.[9]

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.[citation needed]

References

  1. ↑ U.S. Patent 4,194,047
  2. ↑ "Imipenem/cilastatin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy". Drugs 33 (3): 183–241. March 1987. doi:10.2165/00003495-198733030-00001. PMID 3552595. 
  3. ↑ "Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis". The Journal of Antimicrobial Chemotherapy 67 (12): 2793–803. December 2012. doi:10.1093/jac/dks301. PMID 22915465. 
  4. ↑ (in en) Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 497. ISBN 9783527607495. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA497. 
  5. ↑ "Thienamycin: development of imipenen-cilastatin". The Journal of Antimicrobial Chemotherapy 12 Suppl D: 1–35. December 1983. doi:10.1093/jac/12.suppl_d.1. PMID 6365872. 
  6. ↑ "Antibacterial activities of a new stabilized thienamycin, N-formimidoyl thienamycin, in comparison with other antibiotics". Antimicrobial Agents and Chemotherapy 17 (6): 912–7. June 1980. doi:10.1128/aac.17.6.912. PMID 6931548. 
  7. ↑ "Imipenem spectrum of bacterial susceptibility and Resistance". http://www.toku-e.com/Upload/Products/PDS/20120604006407.pdf. 
  8. ↑ "Imipenem-Cilastatin". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 17 January 2017. NBK548708. https://www.ncbi.nlm.nih.gov/books/NBK548708/. Retrieved 19 March 2020. 
  9. ↑ "The risk of seizures among the carbapenems: a meta-analysis". The Journal of Antimicrobial Chemotherapy 69 (8): 2043–55. August 2014. doi:10.1093/jac/dku111. PMID 24744302. 

Further reading

External links

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