Imipenem

Imipenem (trade name Primaxin among others) is an intravenous β-lactam antibiotic discovered 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 play a key role in the treatment of infections not readily treated with other antibiotics.[3]

Imipenem
Clinical data
Trade namesPrimaxin
AHFS/Drugs.comInternational Drug Names
MedlinePlusa686013
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
    CompTox Dashboard (EPA)
    ECHA InfoCard100.058.831
    Chemical and physical data
    FormulaC12H17N3O4S
    Molar mass299.35 g·mol−1
    3D model (JSmol)
      (verify)

    Imipenem was patented in 1975 and approved for medical use in 1985.[4] 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. Thienamycin has antibacterial activity, but is unstable in aqueous solution, so impractical to administer to patients.[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 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.[7]

    Coadministration with cilastatin
    Main article: Imipenem/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.

    gollark: Can you prove that 1 > 0?
    gollark: > 2 * 1.5 = 2
    gollark: Can you mathematically prove that?
    gollark: Wait, are you sure that 3 > 2?
    gollark: Install blood magic?

    References
    1. U.S. Patent 4,194,047
    2. Clissold SP, Todd PA, Campoli-Richards DM (March 1987). "Imipenem/cilastatin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy". Drugs. 33 (3): 183–241. doi:10.2165/00003495-198733030-00001. PMID 3552595.
    3. Vardakas KZ, Tansarli GS, Rafailidis PI, Falagas ME (December 2012). "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. doi:10.1093/jac/dks301. PMID 22915465.
    4. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 497. ISBN 9783527607495.
    5. Kahan FM, Kropp H, Sundelof JG, Birnbaum J (December 1983). "Thienamycin: development of imipenen-cilastatin". The Journal of Antimicrobial Chemotherapy. 12 Suppl D: 1–35. doi:10.1093/jac/12.suppl_d.1. PMID 6365872.
    6. Kesado T, Hashizume T, Asahi Y (June 1980). "Antibacterial activities of a new stabilized thienamycin, N-formimidoyl thienamycin, in comparison with other antibiotics". Antimicrobial Agents and Chemotherapy. 17 (6): 912–7. doi:10.1128/aac.17.6.912. PMC 283902. PMID 6931548.
    7. "Imipenem spectrum of bacterial susceptibility and Resistance" (PDF). Archived from the original (PDF) on 3 March 2016. Retrieved 4 May 2012.
    8. "Imipenem-Cilastatin". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. NCBI Bookshelf. 17 January 2017. PMID 31644018. NBK548708. Retrieved 19 March 2020.
    9. Cannon JP, Lee TA, Clark NM, Setlak P, Grim SA (August 2014). "The risk of seizures among the carbapenems: a meta-analysis". The Journal of Antimicrobial Chemotherapy. 69 (8): 2043–55. doi:10.1093/jac/dku111. PMID 24744302.

    Further reading
    • "Imipenem". Drug Information Portal. U.S. National Library of Medicine.
    This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.