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	J01DH51 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Protein binding	20%
Metabolism	Renal
Biological half-life	38 minutes (children), 60 minutes (adults)
Excretion	Urine (70%)
Identifiers
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
CAS Number	64221-86-9
PubChem (CID)	5282372
DrugBank	DB01598
ChemSpider	4445535
UNII	Q20IM7HE75
KEGG	D00206
ChEBI	CHEBI:51799
ChEMBL	CHEMBL43708
ECHA InfoCard	100.205.470
Chemical and physical data
Formula	C12H17N3O4S
Molar mass	299.347 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(O)/C1=C(\SCC/N=C/N)C[C@H]2N1C(=O)[C@@H]2[C@H](O)C.O
InChI InChI=1S/C12H17N3O4S.H2O/c1-6(16)9-7-4-8(20-3-2-14-5-13)10(12(18)19)15(7)11(9)17;/h5-7,9,16H,2-4H2,1H3,(H2,13,14)(H,18,19);1H2/t6-,7-,9-;/m1./s1 Key:GSOSVVULSKVSLQ-JJVRHELESA-N
(verify)

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 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.^[4] Imipenem has a broad spectrum of activity against aerobic and 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.

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 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. 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.
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. doi:10.1128/aac.17.6.912. PMC 283902. PMID 6931548.
6. "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.

External links

• Imipenem bound to proteins in the PDB