Imipenem

Imipenem
Clinical data
Trade names Primaxin
AHFS/Drugs.com International Drug Names
MedlinePlus a686013
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
    Routes of
    administration    		 IM, IV
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Protein binding 20%
    Metabolism Renal
    Elimination half-life 38 minutes (children), 60 minutes (adults)
    Excretion Urine (70%)
    Identifiers
    CAS Number
    PubChem CID
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    ECHA InfoCard 100.205.470 Edit this at Wikidata
    Chemical and physical data
    Formula C12H17N3O4S
    Molar mass 299.347 g/mol
    3D model (JSmol)
      (verify)

    Imipenem (Primaxin) 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 was patented in 1975.[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.

    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.

    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.

    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 low. At high doses, imipenem is seizurogenic.

    References

    1. ↑ U.S. Patent 4,194,047
    2. ↑ Clissold, SP; Todd, PA; Campoli-Richards, DM (Mar 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 (Dec 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, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 490. ISBN 9783527607495.
    5. ↑ Kahan, FM; Kropp, H; Sundelof, JG; Birnbaum, J (Dec 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, Tadataka; Hashizume, Terutaka; Asahi, Yoshinari (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). Retrieved 4 May 2012.

    Further reading

    • Clissold, SP; Todd, PA; Campoli-Richards, DM (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.
    • Buckley, MM; Brogden, RN; Barradell, LB; Goa, KL (1992). "Imipenem/cilastatin. A reappraisal of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy". Drugs. 44 (3): 408–44. doi:10.2165/00003495-199244030-00008. PMID 1382937.
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