Imipenem: Difference between revisions

{{short description|Carbapenem antibiotic}}

{{Drugbox

| verifiedrevid = 443870020

| IUPAC_name = (5''R'',6''S'')-6-[(1''R'')-1-hydroxyethyl]-3-({2-[(iminomethyl)amino]ethyl}thio)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

| image2 = Imipenem ball-and-stick.png

<!--Clinical data-->

| tradename = Primaxin

| Drugs.com = {{drugs.com|international|imipenem}}

| MedlinePlus = a686013

| DailyMedID = Imipenem

| pregnancy_AU = B3

| pregnancy_US = C

| legal_AU = S4

| legal_CA = Rx-only

| legal_UK = POM

| legal_US = Rx-only

| routes_of_administration = [[Intramuscular injection|IM]], [[Intravenous therapy|IV]]

| ATC_prefix = J01

| ATC_suffix = DH51

<!--Pharmacokinetic data-->

| metabolism = [[Kidney|Renal]]

| protein_bound = 20%

| elimination_half-life = 38 minutes (children), 60 minutes (adults)

| excretion = Urine (70%)

<!--Identifiers-->

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 64221-86-9

| PubChem = 104838

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB01598

| UNII = Q20IM7HE75

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D04515

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 51799

| NIAID_ChemDB =

| PDB_ligand = IM2

| synonyms =

<!--Chemical data-->

| C=12 | H=17 | N=3 | O=4 | S=1

| smiles = O=C(O)/C1=C(\SCC/N=C/N)C[C@H]2N1C(=O)[C@@H]2[C@H](O)C.O

'''Imipenem''' (trade name '''Primaxin''' among others) is a synthetic [[beta-lactam|β-lactam]] [[antibiotic]] belonging to the [[carbapenem]]s chemical class. developed by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s.<ref>{{US Patent|4194047}}</ref> Carbapenems are highly resistant to the [[β-lactamase]] enzymes produced by many multiple drug-resistant Gram-negative bacteria,<ref>{{cite journal | vauthors = Clissold SP, Todd PA, Campoli-Richards DM | title = Imipenem/cilastatin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy | journal = Drugs | volume = 33 | issue = 3 | pages = 183–241 | date = March 1987 | pmid = 3552595 | doi = 10.2165/00003495-198733030-00001 | s2cid = 209144637 }}</ref> thus playing a key role in the treatment of infections not readily treated with other antibiotics.<ref>{{cite journal | vauthors = Vardakas KZ, Tansarli GS, Rafailidis PI, Falagas ME | title = Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis | journal = The Journal of Antimicrobial Chemotherapy | volume = 67 | issue = 12 | pages = 2793–803 | date = December 2012 | pmid = 22915465 | doi = 10.1093/jac/dks301 | doi-access = free }}</ref> It is usually administered through [[intravenous]] injection.

Imipenem was patented in 1975 and approved for medical use in 1985.<ref>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=497|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA497|language=en}}</ref> It was developed 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, thus it is practically of no medicinal use.<ref>{{cite journal | vauthors = Kahan FM, Kropp H, Sundelof JG, Birnbaum J | title = Thienamycin: development of imipenen-cilastatin | journal = The Journal of Antimicrobial Chemotherapy | volume = 12 Suppl D | pages = 1–35 | date = December 1983 | pmid = 6365872 | doi = 10.1093/jac/12.suppl_d.1 }}</ref> Imipenem has a broad spectrum of activity against [[Aerobic organism|aerobic]] and [[Anaerobic organism|anaerobic]], [[Gram-positive]] and [[Gram-negative]] [[bacteria]].<ref>{{cite journal | vauthors = Kesado T, Hashizume T, Asahi Y | title = Antibacterial activities of a new stabilized thienamycin, N-formimidoyl thienamycin, in comparison with other antibiotics | journal = Antimicrobial Agents and Chemotherapy | volume = 17 | issue = 6 | pages = 912–7 | date = June 1980 | pmid = 6931548 | pmc = 283902 | doi = 10.1128/aac.17.6.912 }}</ref> It is particularly important for its activity against ''[[Pseudomonas aeruginosa]]'' and ''[[Enterococcus]]'' species. However, it is not active against [[methicillin-resistant Staphylococcus aureus|MRSA]].

==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]]''.<ref>{{cite web|title=Imipenem spectrum of bacterial susceptibility and Resistance|url=http://www.toku-e.com/Upload/Products/PDS/20120604006407.pdf|access-date=4 May 2012|archive-url=https://web.archive.org/web/20160303210247/http://www.toku-e.com/Upload/Products/PDS/20120604006407.pdf|archive-date=3 March 2016|url-status=dead}}</ref>

===Coadministration with cilastatin===

{{Main|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.<ref>{{cite book | title=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury | url=https://www.ncbi.nlm.nih.gov/books/NBK547852/ | chapter=Imipenem-Cilastatin | website=NCBI Bookshelf | date=17 January 2017 | pmid=31644018 | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK548708/ | access-date=19 March 2020 | id=NBK548708 }}</ref>

Common [[adverse drug reaction]]s 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.<ref>{{cite journal | vauthors = Cannon JP, Lee TA, Clark NM, Setlak P, Grim SA | title = The risk of seizures among the carbapenems: a meta-analysis | journal = The Journal of Antimicrobial Chemotherapy | volume = 69 | issue = 8 | pages = 2043–55 | date = August 2014 | pmid = 24744302 | doi = 10.1093/jac/dku111 | doi-access = free }}</ref>

==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.{{cn|date=March 2023}}

{{Reflist}}

== Further reading ==

{{refbegin}}

* {{cite journal | vauthors = Clissold SP, Todd PA, Campoli-Richards DM | title = Imipenem/cilastatin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy | journal = Drugs | volume = 33 | issue = 3 | pages = 183–241 | date = March 1987 | pmid = 3552595 | doi = 10.2165/00003495-198733030-00001 | s2cid = 209144637 | url = http://adisonline.com/drugs/Abstract/1987/33030/Imipenem_Cilastatin__A_Review_of_its_Antibacterial.1.aspx | access-date = 2011-03-21 | url-status = dead | archive-url = https://web.archive.org/web/20110917183531/http://adisonline.com/drugs/Abstract/1987/33030/Imipenem_Cilastatin__A_Review_of_its_Antibacterial.1.aspx | archive-date = 2011-09-17 }}

* {{cite journal | vauthors = Buckley MM, Brogden RN, Barradell LB, Goa KL | title = Imipenem/cilastatin. A reappraisal of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy | journal = Drugs | volume = 44 | issue = 3 | pages = 408–44 | date = September 1992 | pmid = 1382937 | doi = 10.2165/00003495-199244030-00008 | s2cid = 209143174 | url = http://adisonline.com/drugs/Abstract/1992/44030/Imipenem_Cilastatin__A_Reappraisal_of_its.8.aspx | access-date = 2011-03-21 | url-status = dead | archive-url = https://web.archive.org/web/20120406074426/http://adisonline.com/drugs/Abstract/1992/44030/Imipenem_Cilastatin__A_Reappraisal_of_its.8.aspx | archive-date = 2012-04-06 }}

{{refend}}

== External links ==

* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/rn/74431-23-5 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Imipenem }}

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