Imipenem

Imipenem

Imipenem
Systematic (IUPAC) name
(5R,6S)-6-[(1R)-1-hydroxyethyl]-3-({2-[(iminomethyl)amino]ethyl}thio)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
Clinical data
Trade names Primaxin
AHFS/Drugs.com
MedlinePlus
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
Legal status
Routes of
administration
IM, IV
Pharmacokinetic data
Protein binding 20%
Metabolism Renal
Biological half-life 38 minutes (children), 60 minutes (adults)
Excretion Urine (70%)
Identifiers
CAS Registry Number  Y
ATC code J01
PubChem CID:
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  Y
ChEMBL  Y
Chemical data
Formula C12H17N3O4S
Molecular mass 299.347 g/mol
 Y   

Imipenem (Primaxin) is an intravenous β-lactam antibiotic discovered by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in 1980.[1] It was the first member of the carbapenem class of antibiotics. 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]

It was discovered via a lengthy trial-and-error search for a more stable version of the natural product anaerobic, Gram-positive and Gram-negative bacteria.[5] It is particularly important for its activity against Pseudomonas aeruginosa and the Enterococcus species. It is not active against MRSA, however.

Contents

  • Mechanism of action 1
  • Spectrum of bacterial susceptibility and resistance 2
  • Coadministration with cilastatin 3
  • Adverse effects 4
  • References 5
  • External links 6
  • Further reading 7

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.[6]

Coadministration with cilastatin

Imipenem is rapidly degraded by the renal enzyme dehydropeptidase 1 when administered alone, and is 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 seizuregenic.

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.  
  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.  
  4. ^ 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.  
  5. ^ 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.  
  6. ^ "Imipenem spectrum of bacterial susceptibility and Resistance" (PDF). Retrieved 4 May 2012. 

External links

  • Imipenem bound to proteins in the PDB

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.  
  • 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.