Imipenem

Clinical data
Trade names| Primaxin
AHFS/Drugs.com| International Drug Names
MedlinePlus| a686013
License data|

* US DailyMed: Imipenem

Pregnancy
category|

* AU: B3

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
Elimination 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 Y

PubChem CID|

* 104838

DrugBank|

* DB01598 Y

ChemSpider|

* 4445535 Y

UNII|

* Q20IM7HE75

KEGG|

* D04515 Y

ChEBI|

* CHEBI:51799 Y

ChEMBL|

* ChEMBL43708 Y

PDB ligand|

* IM2 (PDBe, RCSB PDB)

CompTox Dashboard (EPA)|

* DTXSID2023143

ECHA InfoCard| 100.058.831
Chemical and physical data
Formula| C12H17N3O4S
Molar mass| 299.35 g·mol−1
3D model (JSmol)|

* 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 Y

* Key:GSOSVVULSKVSLQ-JJVRHELESA-N Y

(verify)

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 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.

## Contents

* 1 Medical uses
* 1.1 Spectrum of bacterial susceptibility and resistance
* 1.2 Coadministration with cilastatin
* 2 Adverse effects
* 3 Mechanism of action
* 4 References
* 5 Further reading
* 6 External links

## Medical uses[edit]

### Spectrum of bacterial susceptibility and resistance[edit]

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[edit]

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[edit]

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[edit]

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.

## References[edit]

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. S2CID 209144637.
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[edit]

* 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. S2CID 209144637. Archived from the original on 2011-09-17. Retrieved 2011-03-21.
* Buckley MM, Brogden RN, Barradell LB, Goa KL (September 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. S2CID 209143174. Archived from the original on 2012-04-06. Retrieved 2011-03-21.

## External links[edit]

* "Imipenem". Drug Information Portal. U.S. National Library of Medicine.

* v
* t
* e

Antibacterials active on the cell wall and envelope (J01C-J01D)

Beta-lactams
(inhibit synthesis
of peptidoglycan
layer of bacterial
cell wall by binding
to and inhibiting
PBPs, a group of
D-alanyl-D-alanine
transpeptidases)|

| Penicillins (Penams)|

| Narrow
spectrum|

| β-lactamase sensitive
(1st generation)|

* Benzylpenicillin (G)#
* Benzathine benzylpenicillin#
* Procaine benzylpenicillin#
* Phenoxymethylpenicillin (V)#
* Propicillin‡
* Pheneticillin‡
* Azidocillin‡
* Clometocillin‡
* Penamecillin‡

|

β-lactamase resistant
(2nd generation)|

* Cloxacillin# (Dicloxacillin
* Flucloxacillin)
* Oxacillin
* Nafcillin
* Methicillin‡

Extended
spectrum|

| Aminopenicillins (3rd generation)|

* Amoxicillin#
* Ampicillin# (Pivampicillin
* Hetacillin‡
* Bacampicillin‡
* Metampicillin‡
* Talampicillin‡)
* Epicillin‡

|

Carboxypenicillins (4th generation)|

* Ticarcillin
* Carbenicillin‡ / Carindacillin‡
* Temocillin‡

Ureidopenicillins (4th generation)|

* Piperacillin
* Azlocillin‡
* Mezlocillin‡

Other|

* Mecillinam (Pivmecillinam)
* Sulbenicillin‡

Carbapenems / Penems|

* Carbapenems (Ertapenem
* Antipseudomonal (Doripenem
* Imipenem
* Meropenem)
* Biapenem‡
* Panipenem)
* Penems (Faropenem
* Ritipenem§)

Cephems
Cephalosporins
Cephamycins
Carbacephems|

| 1st generation|

* Cefazolin#
* Cefalexin #
* Cefadroxil
* Cefapirin
* Cefazedone‡
* Cefazaflur‡
* Cefradine‡
* Cefroxadine‡
* Ceftezole‡
* Cefaloglycin‡
* Cefacetrile‡
* Cefalonium‡
* Cefaloridine‡
* Cefalotin
* Cefatrizine‡

|

2nd generation|

* Cefaclor
* Cefprozil
* Cefuroxime
* Cefuroxime axetil
* Cefamandole‡
* Cefonicid‡
* Ceforanide‡
* Cefuzonam‡
* Cephamycin (Cefoxitin
* Cefotetan
* Cefminox‡
* Cefbuperazone‡
* Cefmetazole‡)
* Carbacephem (Loracarbef‡)

3rd generation|

* Cefixime#
* Ceftriaxone#
* Cefotaxime#
* Antipseudomonal (Ceftazidime#
* Cefoperazone)
* Cefdinir
* Cefcapene
* Cefdaloxime
* Ceftizoxime
* Cefmenoxime
* Cefpiramide
* Cefpodoxime
* Ceftibuten
* Cefditoren
* Cefotiam‡
* Cefetamet‡
* Cefodizime‡
* Cefpimizole‡
* Cefsulodin‡
* Cefteram‡
* Ceftiolene‡
* Oxacephem (Flomoxef
* Latamoxef‡)

4th generation|

* Cefepime
* Cefozopran‡
* Cefpirome
* Cefquinome‡

5th generation|

* Ceftaroline fosamil
* Ceftolozane
* Ceftobiprole

Siderophore|

* Cefiderocol#

Veterinary|

* Ceftiofur
* Cefquinome
* Cefovecin

Monobactams|

* Aztreonam
* Tigemonam‡
* Carumonam‡
* Nocardicin A‡

β-lactamase inhibitors|

* Penam (Sulbactam
* Tazobactam)
* Clavam (Clavulanic acid)
* non-β-lactam (Relebactam
* Avibactam
* Vaborbactam)

Combinations|

* Amoxicillin/clavulanic acid#
* Ampicillin/flucloxacillin
* Ampicillin/sulbactam (Sultamicillin)
* Benzathine benzylpenicillin/procaine benzylpenicillin
* Cefoperazone/sulbactam
* Ceftazidime/avibactam
* Ceftolozane/tazobactam
* Imipenem/cilastatin#
* Imipenem/cilastatin/relebactam
* Meropenem/vaborbactam
* Panipenem/betamipron
* Piperacillin/tazobactam
* Ticarcillin/clavulanic acid

Polypeptides|

| Glycopeptides
Lipoglycopeptides|

* Inhibit PG chain elongation: Vancomycin# (Oritavancin
* Telavancin)
* Teicoplanin (Dalbavancin)
* Ristocetin‡
* Avoparcin
* Inhibit autolysin: Corbomycin (not approved)

|

Lipopeptides|

* Insert into bacterial cell wall causing perforation and depolarization: Daptomycin
* Surfactin

Polymyxins|

* Bind to LPS in the outer bacterial membrane, acting in detergent-like fashion: Colistin
* Polymyxin B

Other|

* Inhibits PG elongation and crosslinking: Ramoplanin§

Intracellular|

* Inhibit PG subunit synthesis and transport: NAM synthesis inhibition (Fosfomycin)
* DADAL/AR inhibitors (Cycloserine)
* bactoprenol inhibitors (Bacitracin)

Other|

* Hydrolyze NAM-NAG
* lysozyme
* Tyrothricin
* Gramicidin
* Tyrocidine
* Isoniazid#
* Teixobactin

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

* v
* t
* e

GABA receptor modulators

Ionotropic|

| GABAA|

* Agonists: (+)-Catechin
* Bamaluzole
* Barbiturates (e.g., phenobarbital)
* Beta-Alanine
* BL-1020
* DAVA
* Dihydromuscimol
* GABA
* Gabamide
* GABOB
* Gaboxadol (THIP)
* Homotaurine (tramiprosate, 3-APS)
* Ibotenic acid
* iso-THAZ
* iso-THIP
* Isoguvacine
* Isomuscimol
* Isonipecotic acid
* Kojic amine
* L-838,417
* Lignans (e.g., honokiol)
* Methylglyoxal
* Monastrol
* Muscimol
* Nefiracetam
* Neuroactive steroids (e.g., allopregnanolone)
* Org 20599
* PF-6372865
* Phenibut
* Picamilon
* P4S
* Progabide
* Propofol
* Quisqualamine
* SL-75102
* Taurine
* TACA
* TAMP
* Terpenoids (e.g., borneol)
* Thiomuscimol
* Tolgabide
* ZAPA

* Positive modulators (abridged; see here for a full list): α-EMTBL
* Alcohols (e.g., drinking alcohol, 2M2B)
* Anabolic steroids
* Avermectins (e.g., ivermectin)
* Barbiturates (e.g., phenobarbital)
* Benzodiazepines (e.g., diazepam)
* Bromide compounds (e.g., potassium bromide)
* Carbamates (e.g., meprobamate)
* Carbamazepine
* Chloralose
* Chlormezanone
* Clomethiazole
* Dihydroergolines (e.g., ergoloid (dihydroergotoxine))
* Etazepine
* Etifoxine
* Fenamates (e.g., mefenamic acid)
* Flavonoids (e.g., apigenin, hispidulin)
* Fluoxetine
* Flupirtine
* Imidazoles (e.g., etomidate)
* Kava constituents (e.g., kavain)
* Lanthanum
* Loreclezole
* Monastrol
* Neuroactive steroids (e.g., allopregnanolone, cholesterol, THDOC)
* Niacin
* Niacinamide
* Nonbenzodiazepines (e.g., β-carbolines (e.g., abecarnil), cyclopyrrolones (e.g., zopiclone), imidazopyridines (e.g., zolpidem), pyrazolopyrimidines (e.g., zaleplon))
* Norfluoxetine
* Petrichloral
* Phenols (e.g., propofol)
* Phenytoin
* Piperidinediones (e.g., glutethimide)
* Propanidid
* Pyrazolopyridines (e.g., etazolate)
* Quinazolinones (e.g., methaqualone)
* Retigabine (ezogabine)
* ROD-188
* Skullcap constituents (e.g., baicalin)
* Stiripentol
* Sulfonylalkanes (e.g., sulfonmethane (sulfonal))
* Topiramate
* Valerian constituents (e.g., valerenic acid)
* Volatiles/gases (e.g., chloral hydrate, chloroform, diethyl ether, paraldehyde, sevoflurane)

* Antagonists: Bicuculline
* Coriamyrtin
* Dihydrosecurinine
* Gabazine (SR-95531)
* Hydrastine
* Hyenachin (mellitoxin)
* PHP-501
* Pitrazepin
* Securinine
* Sinomenine
* SR-42641
* SR-95103
* Thiocolchicoside
* Tutin

* Negative modulators: 1,3M1B
* 3M2B
* 11-Ketoprogesterone
* 17-Phenylandrostenol
* α5IA (LS-193,268)
* β-CCB
* β-CCE
* β-CCM
* β-CCP
* β-EMGBL
* Anabolic steroids
* Amiloride
* Anisatin
* β-Lactams (e.g., penicillins, cephalosporins, carbapenems)
* Basmisanil
* Bemegride
* Bicyclic phosphates (TBPS, TBPO, IPTBO)
* BIDN
* Bilobalide
* Bupropion
* CHEB
* Chlorophenylsilatrane
* Cicutoxin
* Cloflubicyne
* Cyclothiazide
* DHEA
* DHEA-S
* Dieldrin
* (+)-DMBB
* DMCM
* DMPC
* EBOB
* Etbicyphat
* FG-7142 (ZK-31906)
* Fiproles (e.g., fipronil)
* Flavonoids (e.g., amentoflavone, oroxylin A)
* Flumazenil
* Fluoroquinolones (e.g., ciprofloxacin)
* Flurothyl
* Furosemide
* Golexanolone
* Iomazenil (123I)
* IPTBO
* Isopregnanolone (sepranolone)
* L-655,708
* Laudanosine
* Leptazol
* Lindane
* MaxiPost
* Morphine
* Morphine-3-glucuronide
* MRK-016
* Naloxone
* Naltrexone
* Nicardipine
* Nonsteroidal antiandrogens (e.g., apalutamide, bicalutamide, enzalutamide, flutamide, nilutamide)
* Oenanthotoxin
* Pentylenetetrazol (pentetrazol)
* Phenylsilatrane
* Picrotoxin (i.e., picrotin, picrotoxinin and dihydropicrotoxinin)
* Pregnenolone sulfate
* Propybicyphat
* PWZ-029
* Radequinil
* Ro 15-4513
* Ro 19-4603
* RO4882224
* RO4938581
* Sarmazenil
* SCS
* Suritozole
* TB-21007
* TBOB
* TBPS
* TCS-1105
* Terbequinil
* TETS
* Thujone
* U-93631
* Zinc
* ZK-93426

|

GABAA-ρ|

* Agonists: BL-1020
* CACA
* CAMP
* Homohypotaurine
* GABA
* GABOB
* Ibotenic acid
* Isoguvacine
* Muscimol
* N4-Chloroacetylcytosine arabinoside
* Picamilon
* Progabide
* TACA
* TAMP
* Thiomuscimol
* Tolgabide

* Positive modulators: Allopregnanolone
* Alphaxolone
* ATHDOC
* Lanthanides

* Antagonists: (S)-2-MeGABA
* (S)-4-ACPBPA
* (S)-4-ACPCA
* 2-MeTACA
* 3-APMPA
* 4-ACPAM
* 4-GBA
* cis-3-ACPBPA
* CGP-36742 (SGS-742)
* DAVA
* Gabazine (SR-95531)
* Gaboxadol (THIP)
* I4AA
* Isonipecotic acid
* Loreclezole
* P4MPA
* P4S
* SKF-97541
* SR-95318
* SR-95813
* TPMPA
* trans-3-ACPBPA
* ZAPA

* Negative modulators: 5α-Dihydroprogesterone
* Bilobalide
* Loreclezole
* Picrotoxin (picrotin, picrotoxinin)
* Pregnanolone
* ROD-188
* THDOC
* Zinc

Metabotropic|

| GABAB|

* Agonists: 1,4-Butanediol
* 3-APPA
* 4-Fluorophenibut
* Aceburic acid
* Arbaclofen
* Arbaclofen placarbil
* Baclofen
* BL-1020
* GABA
* Gabamide
* GABOB
* GBL
* GHB
* GHBAL
* GHV
* GVL
* Isovaline
* Lesogaberan
* Phenibut
* Picamilon
* Progabide
* Sodium oxybate
* SKF-97,541
* SL 75102
* Tolgabide
* Tolibut

* Positive modulators: ADX-71441
* BHF-177
* BHFF
* BSPP
* CGP-7930
* CGP-13501
* GS-39783
* rac-BHFF
* KK-92A

* Antagonists: 2-Hydroxysaclofen
* CGP-35348
* CGP-46381
* CGP-52432
* CGP-54626
* CGP-55845
* CGP-64213
* DAVA
* Homotaurine (tramiprosate, 3-APS)
* Phaclofen
* Saclofen
* SCH-50911
* SKF-97541

* Negative modulators: Compound 14

|

See also
Receptor/signaling modulators
GABAA receptor positive modulators
GABA metabolism/transport modulators

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*[US]: United States
*[AU]: Australia
*[CA]: Canada
*[UK]: United Kingdom
*[CID]: Compound ID
*[EPA]: U.S. Environmental Protection Agency
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[GABA]: γ-Aminobutyric acid
*[GABAA]: γ-Aminobutyric acid A receptor
*[GABAA-ρ]: γ-Aminobutyric acid A-rho receptor
*[GABAB]: γ-Aminobutyric acid B receptor