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Revision as of 14:00, 22 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 461895018 of page Kanamycin for the Chem/Drugbox validation project (updated: 'DrugBank').  Latest revision as of 05:29, 25 November 2024 edit OAbot (talk | contribs)Bots441,761 editsm Open access bot: pmc updated in citation with #oabot. 
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{{Short description|Antibiotic}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
{{Distinguish|Kanamycin B|Keanumycin}}
{{Use dmy dates|date=March 2024}}
{{Drugbox {{Drugbox
| verifiedrevid = 461938453
| Verifiedfields = changed
| verifiedrevid = 400126564
| IUPAC_name = 2-(aminomethyl)- 6-oxy- 2-hydroxy- cyclohexoxy]- tetrahydropyran- 3,4,5-triol
| image = Kanamycin A.svg | image = Kanamycin A.svg
| alt =


<!--Clinical data-->
| tradename =
| Drugs.com = {{drugs.com|monograph|kanamycin-sulfate}} | Drugs.com = {{drugs.com|monograph|kanamycin-sulfate}}
| pregnancy_category = D | pregnancy_category = D
| routes_of_administration = By mouth, ], ]
| legal_status = ?
| ATC_prefix = A07
| routes_of_administration = Oral, ], ]
| ATC_suffix = AA08
| ATC_supplemental = {{ATC|J01|GB04}} {{ATC|S01|AA24}}

| legal_status =


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
| bioavailability = very low after oral delivery | bioavailability = very low after by mouth delivery
| metabolism = Unknown | metabolism = Unknown
| elimination_half-life = 2 hours 30 minutes | elimination_half-life = 2 hours 30 minutes
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<!--Identifiers--> <!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 59-01-8 | CAS_number = 59-01-8
| ATC_prefix = A07
| ATC_suffix = AA08
| ATC_supplemental = {{ATC|J01|GB04}} {{ATC|S01|AA24}}
| PubChem = 6032 | PubChem = 6032
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5810 | ChemSpiderID = 5810
| UNII_Ref = {{fdacite|changed|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = RUC37XUP2P | UNII = EQK9Q303C5
| ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17630 | ChEBI = 17630
| ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1384 | ChEMBL = 1384
| PDB_ligand = KAN
| CAS_number2_Ref = {{cascite|correct|CAS}}
| CAS_number2 = 8063-07-8
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII2 = RUC37XUP2P
| synonyms = K/KAN/HLK/KM<ref>{{cite web |title=Antibiotic abbreviations list |url=https://microbiologie-clinique.com/antibiotic-family-abbreviation.html |access-date=22 June 2023}}</ref>


<!--Chemical data--> <!--Chemical data-->
| IUPAC_name = 2-(aminomethyl)- 6-oxy- 2-hydroxy- cyclohexoxy]- tetrahydropyran- 3,4,5-triol
| C=18 | H=36 | N=4 | O=11
| C=18 | H=36 | N=4 | O=11
| molecular_weight = 484.499
| smiles = O(2(O)(O1O(CN)(O)(O)1O)(N)C2N)3O((O)(N)3O)CO | smiles = O(2(O)(O1O(CN)(O)(O)1O)(N)C2N)3O((O)(N)3O)CO
| InChI = 1/C18H36N4O11/c19-2-6-10(25)12(27)13(28)18(30-6)33-16-5(21)1-4(20)15(14(16)29)32-17-11(26)8(22)9(24)7(3-23)31-17/h4-18,23-29H,1-3,19-22H2/t4-,5+,6-,7-,8+,9-,10-,11-,12+,13-,14-,15+,16-,17-,18-/m1/s1
| InChIKey = SBUJHOSQTJFQJX-NOAMYHISBU
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C18H36N4O11/c19-2-6-10(25)12(27)13(28)18(30-6)33-16-5(21)1-4(20)15(14(16)29)32-17-11(26)8(22)9(24)7(3-23)31-17/h4-18,23-29H,1-3,19-22H2/t4-,5+,6-,7-,8+,9-,10-,11-,12+,13-,14-,15+,16-,17-,18-/m1/s1 | StdInChI = 1S/C18H36N4O11/c19-2-6-10(25)12(27)13(28)18(30-6)33-16-5(21)1-4(20)15(14(16)29)32-17-11(26)8(22)9(24)7(3-23)31-17/h4-18,23-29H,1-3,19-22H2/t4-,5+,6-,7-,8+,9-,10-,11-,12+,13-,14-,15+,16-,17-,18-/m1/s1
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| StdInChIKey = SBUJHOSQTJFQJX-NOAMYHISSA-N | StdInChIKey = SBUJHOSQTJFQJX-NOAMYHISSA-N
}} }}
<!-- Definition and medical uses -->
'''Kanamycin A''',<ref>{{cite book| vauthors = Elks J, Ganellin DR |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA717 |date=1990 |publisher=Springer |doi=10.1007/BF00171763 |pages=717– | s2cid = 122125855 }}</ref> often referred to simply as '''kanamycin''', is an ] used to treat severe ] and ].<ref name=AHFS2016/> It is not a first line treatment.<ref name=AHFS2016/> It is used ], ], or ].<ref name=AHFS2016/> Kanamycin is recommended for short-term use only, usually from 7 to 10 days.<ref name=AHFS2016/> Since antibiotics only show activity against bacteria, it is ineffective in ].<ref name=AHFS2016>{{cite web|title=Kanamycin Sulfate|url=https://www.drugs.com/monograph/kanamycin-sulfate.html|publisher=The American Society of Health-System Pharmacists|access-date=6 December 2016|url-status=live|archive-url=https://web.archive.org/web/20170910221516/https://www.drugs.com/monograph/kanamycin-sulfate.html|archive-date=10 September 2017}}</ref>

<!-- Side effects and mechanism -->
Common side effects include hearing and balance problems.<ref name=AHFS2016/> Kidney problems may also occur.<ref name=AHFS2016/> Kanamycin is not recommended during pregnancy as it may harm the baby.<ref name=AHFS2016/> It is likely safe during ].<ref>{{cite web|title=Kanamycin (Kantrex) Use During Pregnancy|url=https://www.drugs.com/pregnancy/kanamycin.html|website=www.drugs.com|access-date=7 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220222732/https://www.drugs.com/pregnancy/kanamycin.html|archive-date=20 December 2016}}</ref> Kanamycin is in the ] family of medications.<ref name=AHFS2016/> It has the weakest antibacterial capabilities of all compounds in this family when used clinically, which is partially due to its increased toxicity in comparison to other aminoglycosides.<ref>{{cite journal | vauthors=Lounis N, Truffot-Pernot C, Grosset J | title=Which aminoglycoside or fluoroquinolone is more active against Mycobacterium tuberculosis in mice? | journal = Antimicrobial Agents and Chemotherapy | date = March 1977 | volume = 41 | issue = 3 | pages=607-610 | pmid = 9056001 | doi = 10.1128/aac.41.3.607| pmc = 163759 }}</ref> It works by blocking the production of proteins that are required for bacterial survival.<ref name=AHFS2016/>

<!-- History and culture -->
Kanamycin was first isolated in 1957 by ] from the bacterium '']''.<ref name=AHFS2016/><ref>{{cite book |last1=Sneader |first1=Walter | name-list-style = vanc |title=Drug Discovery: A History|date=2005|publisher=John Wiley & Sons|isbn=9780471899792|page=302|url=https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA302}}</ref> It was removed from the ] in 2019.<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | year = 2019 | title = Executive summary: the selection and use of essential medicines 2019: report of the 22nd WHO Expert Committee on the selection and use of essential medicines | publisher = World Health Organization | location = Geneva | author-link = World Health Organization | hdl = 10665/325773 | id = WHO/MVP/EMP/IAU/2019.05. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref>{{cite book | vauthors = ((World Health Organization)) | year = 2019 | title = The selection and use of essential medicines: report of the WHO Expert Committee on Selection and Use of Essential Medicines, 2019 (including the 21st WHO Model List of Essential Medicines and the 7th WHO Model List of Essential Medicines for Children) | publisher = World Health Organization | location = Geneva | author-link = World Health Organization | hdl = 10665/330668 | id = WHO technical report series;1021 | hdl-access=free | isbn = 9789241210300 | issn = 0512-3054 }}</ref> It is no longer marketed in the United States.<ref name=AHFS2016/>

==Medical uses==

===Spectrum of activity===
Kanamycin is indicated for short-term treatment of bacterial infections caused by one or more of the following pathogens: '']'', '']'' species (both indole-positive and indole-negative), '']'', '']'', '']'', and '']'' species. In cases of serious infection when the causative organism is unknown, Kanamycin injection in conjunction with a ]- or ]-type drug may be given initially before obtaining results of susceptibility testing.{{cn|date=August 2022}}

Kanamycin does not treat viral infections.<ref name=":0">{{Cite web|url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0010823/?report=details|title=Kanamycin (By injection)|url-status=live|archive-url=https://web.archive.org/web/20170910144332/https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0010823/?report=details|archive-date=10 September 2017}}</ref>

===Pregnancy and breastfeeding===

Kanamycin is ] D in the United States.<ref name=":0" />

Kanamycin enters breast milk in small amounts. The manufacturer therefore advises that people should either stop breastfeeding or kanamycin. The ] considers kanamycin okay in breastfeeding.<ref>{{cite book |last1=Briggs |first1=Gerald | name-list-style = vanc |title=Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk|date=2011|publisher=Lippincott Williams & Wilkins|page=787}}</ref>

===Children===

Kanamycin should be used with caution in newborns due to the risk of increased drug concentration resulting from immature kidney function.<ref name=":0" />

==Side effects==

Serious ]s include ] or loss of hearing, ], and ] reactions to the ].<ref>{{Citation | title = Consumer Drug Information: Kanamycin | date = 2 April 2008 | url = https://www.drugs.com/cdi/kanamycin.html | access-date = 4 May 2008 | url-status = live | archive-url = https://web.archive.org/web/20080503110336/http://www.drugs.com/cdi/kanamycin.html | archive-date = 3 May 2008 }}</ref> ] is a common quality among aminoglycosides, and its rate of incidence in kanamycin is around 3-10%.<ref>{{cite book | vauthors = Chan ED, Chatterjee D, Iseman MD, Heifets LB | chapter= Pyrazinamide, ethambutol, ethionamide, and aminoglycosides | title=Tuberculosis | editor=Rom WN, Garay SM | date=2004 | edition = 2 |publisher=Lippincott Williams & Wilkins}}</ref>

Other side effects include:<ref name=":0" />

Gastrointestinal effects
* Nausea, vomiting, diarrhea
Musculoskeletal effects
* Myasthenia gravis
Neurologic effects
* Headache
* Paresthesias
* Blurring of vision
* Neuromuscular blockade
Metabolic effects
* Malabsorption syndrome

==Mechanism==

Kanamycin works by interfering with protein synthesis. It binds to the ] of the bacterial ribosome. This results in incorrect alignment with the mRNA and eventually leads to a misread that causes the wrong amino acid to be placed into the peptide. This leads to nonfunctional peptide chains.<ref>{{cite web|date=17 August 2016| work = DrugBank |title=Kanamycin |url=https://www.drugbank.ca/drugs/DB01172 }}</ref>

==Bacterial Resistance==
] to kanamycin is a serious and increasing phenomenon, which is very concerning for its use in treating ] and other multidrug-resistant ] bacterial infections. This is due in part to possible cross-resistance between kanamycin and other aminoglycosides, such as ], ], and ].<ref>{{cite journal | vauthors=Das DJ, Shankar A, Johnson JB, Thomas S | title=Critical insights into antibiotic resistance transferability in probiotic Lactobacillus | journal = Nutrition | volume = 69 | date = 2020 | doi = 10.1016/j.nut.2019.110567}}</ref> Resistance to these aminoglycosides is due to mutations in the ] gene (rrs) within the 30S subunit that stops the antibacterial from binding tightly to the gene.<ref>{{cite journal | vauthors= Jugheli L, Bzekalava N, de Rijk P, Fissette K, Portaels F, Rigouts L | title=High level of cross-resistance between kanamycin, amikacin, and capreomycin among Mycobacterium tuberculosis isolates from Georgia and a close relation with mutations in the rrs gene | journal=Antimicrobial Agents and Chemotherapy | volume = 53 | issue = 12 | pages= 5064-5068 | date = 2009 | PMID = 19752274 | doi = 10.1128/AAC.00851-09| pmc = 2786337 }}</ref> These mutations are most commonly identified through a ] at the position 1401.<ref>{{cite journal | vauthors = Ley SD, Pillay S, Streicher EM, van der Heijden YF, Sirgel F, Derendinger B, de Kock M, Gagneux S, Warren RM, Theron G, de Vos M | display-authors = 6 | journal = Antimicrobial Agents and Chemotherapy | volume = 65 | issue = 7 | date = July 2021 | pmid = 33903113 | doi = 10.1128/AAC.02502-20| title=Melting the eis: Nondetection of Kanamycin Resistance Markers by Routine Diagnostic Tests and Identification of New eis Promoter Variants| pmc = 8218670 }}</ref>

==Composition==

Kanamycin is a mixture of three main components: kanamycin A, B, and C. Kanamycin A is the major component in kanamycin.<ref>{{cite web | title = Kanamycin | url = https://pubchem.ncbi.nlm.nih.gov/compound/6032 | work = PubChem | publisher = U.S. National Library of Medicine }}</ref> The effects of these components do not appear to be widely studied as individual compounds when used against prokaryotic and eukaryotic cells.{{cn|date=August 2022}}

==Biosynthesis==

While the main product produced by ''Streptomyces kanamyceticus'' is kanamycin A, additional products are also produced, including kanamycin B, kanamycin C, kanamycin D and kanamycin X.<ref>{{Cite web |title=Kanamycin Sulfate, USP |url=https://toku-e.com/kanamycin-sulfate-usp/ |access-date=2024-06-28 |website=TOKU-E |language=en}}</ref>

The kanamycin biosynthetic pathway can be divided into two parts. The first part is common to several aminoglycoside antibiotics, such as ] and ]. In it a unique aminocyclitol, 2-deoxystreptamine, is biosynthesized from ] in four steps. At this point the kanamycin pathway splits into two branches due to the promiscuity of the next enzyme, which can utilize two different glycosyl donors - UDP-N-acetyl-α-<small>D</small>-glucosamine and UDP-α-<small>D</small>-glucose. One of the branches forms kanamycin C and kanamycin B, while the other branch forms kanamycin D and kanamycin X. However, both kanamycin B and kanamycin D can be converted to kanamycin A, so both branches of the pathway converge at kanamycin A.<ref>{{cite web|title=kanamycin biosynthesis pathway | work = MetaCyc|url=http://www.biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-7000&detail-level=3 |access-date=30 September 2014}}</ref>

==Use in research==

Kanamycin is used in molecular biology as a selective agent most commonly to isolate ] (e.g., '']'') which have taken up genes (e.g., of ]s) coupled to a gene coding for kanamycin resistance (primarily Neomycin phosphotransferase II ). Bacteria that have been ] with a plasmid containing the kanamycin resistance gene are plated on kanamycin (50-100&nbsp;μg/mL) containing ] plates or are grown in media containing kanamycin (50-100&nbsp;μg/mL). Only the bacteria that have successfully taken up the kanamycin resistance gene become resistant and will grow under these conditions. As a powder, kanamycin is white to off-white and is soluble in water (50&nbsp;mg/mL).{{cn|date=August 2022}}

At least one such gene, ''Atwbc19''<ref>{{cite web |url=http://www.isb.vt.edu/articles/oct0501.htm |title=Horizontal Gene Transfer: Plant vs. Bacterial Genes for Antibiotic Resistance Scenario's—What's the Difference? |publisher=Isb.vt.edu |access-date=24 June 2013 |url-status=live |archive-url=https://web.archive.org/web/20130606034029/http://www.isb.vt.edu/articles/oct0501.htm |archive-date=6 June 2013 }}</ref> is native to a plant species, of comparatively large size and its coded protein acts in a manner which decreases the possibility of ] from the plant to bacteria; it may be incapable of giving resistance to bacteria even if gene transfer occurs.{{cn|date=December 2022}}

===KanMX marker===
The selection marker kanMX is a hybrid gene consisting of a bacterial aminoglycoside phosphotransferase (kan<sup>r</sup> from ] Tn903) under control of the strong TEF ] from '']''.<ref name="Wach1994">{{cite journal | vauthors = Wach A, Brachat A, Pöhlmann R, Philippsen P | title = New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae | journal = Yeast | volume = 10 | issue = 13 | pages = 1793–1808 | date = December 1994 | pmid = 7747518 | doi = 10.1002/yea.320101310 | s2cid = 25158247 }}</ref><ref name="Steiner1994">{{cite journal | vauthors = Steiner S, Philippsen P | title = Sequence and promoter analysis of the highly expressed TEF gene of the filamentous fungus Ashbya gossypii | journal = Molecular & General Genetics | volume = 242 | issue = 3 | pages = 263–271 | date = February 1994 | pmid = 8107673 | doi = 10.1007/BF00280415 | s2cid = 19928246 }}</ref>

Mammalian cells, yeast, and other ]s acquire resistance to ] (= G418, an aminoglycoside antibiotic similar to kanamycin) when transformed with a kanMX marker. In yeast, the kanMX marker avoids the requirement of ] markers. In addition, the kanMX marker renders ''E. coli'' resistant to kanamycin. In ]s the KanMX ] is used with an additional bacterial promoter. Several versions of the kanMX cassette are in use, e.g. kanMX1-kanMX6. They primarily differ by additional restriction sites and other small changes around the actual ].<ref name="Wach1994" /><ref name="Wach1996">{{cite journal | vauthors = Wach A | title = PCR-synthesis of marker cassettes with long flanking homology regions for gene disruptions in S. cerevisiae | journal = Yeast | volume = 12 | issue = 3 | pages = 259–265 | date = March 1996 | pmid = 8904338 | doi = 10.1002/(SICI)1097-0061(19960315)12:3<259::AID-YEA901>3.0.CO;2-C | s2cid = 10450123 }}</ref>

== Antibiotic Conjugated Nanoparticle Synthesis ==
Antibiotic resistance or development of multi-drug resistant bacterial strains is a key challenge for treating bacterial infections. With limited research being carried out to design and develop new antibiotics, novel approaches like functionalizing antibiotic to metal ]s surface to treat resistant bacterial strains have been studied. Kanamycin functionalized gold-nanoparticles (Kan-GNPs) were synthesized and tested for its antibacterial activity against both gram positive and gram negative strains. A dose dependent antibacterial activity was noted for Kan-GNPs in comparison to free kanamycin.<ref>{{cite journal | vauthors = Payne JN, Waghwani HK, Connor MG, Hamilton W, Tockstein S, Moolani H, Chavda F, Badwaik V, Lawrenz MB, Dakshinamurthy R | display-authors = 6 | title = Novel Synthesis of Kanamycin Conjugated Gold Nanoparticles with Potent Antibacterial Activity | journal = Frontiers in Microbiology | volume = 7 | pages = 607 | date = May 2016 | pmid = 27330535 | pmc = 4908860 | doi = 10.3389/fmicb.2016.00607 | doi-access = free }}</ref>

== References ==
{{reflist}}

{{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}}
{{AminoglycosideAntiBiotics}}
{{Portal bar|Medicine}}

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