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| Clinical data | |
|---|---|
| Other names | K/KAN/HLK/KM[1] |
| AHFS/Drugs.com | Monograph |
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| Routes of administration | By mouth,intravenous,intramuscular |
| ATC code | |
| Pharmacokinetic data | |
| Bioavailability | very low after by mouth delivery |
| Metabolism | Unknown |
| Eliminationhalf-life | 2 hours 30 minutes |
| Excretion | Urine (as unchanged drug) |
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| CAS Number | |
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| DrugBank |
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| ChemSpider |
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| UNII | |
| ChEBI | |
| ChEMBL | |
| PDB ligand | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.000.374 |
| Chemical and physical data | |
| Formula | C18H36N4O11 |
| Molar mass | 484.503 g·mol−1 |
| 3D model (JSmol) | |
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Kanamycin A,[2] often referred to simply askanamycin, is anantibiotic used to treat severebacterial infections andtuberculosis.[3] It is not a first line treatment.[3] It is usedby mouth,injection into a vein, orinjection into a muscle.[3] Kanamycin is recommended for short-term use only, usually from 7 to 10 days.[3] Since antibiotics only show activity against bacteria, it is ineffective inviral infections.[3]
Common side effects include hearing and balance problems.[3] Kidney problems may also occur.[3] Kanamycin is not recommended during pregnancy as it may harm the baby.[3] It is likely safe duringbreastfeeding.[4] Kanamycin is in theaminoglycoside family of medications.[3] 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.[5] It works by blocking the production of proteins that are required for bacterial survival.[3]
Kanamycin was first isolated in 1957 byHamao Umezawa from the bacteriumStreptomyces kanamyceticus.[3][6] It was removed from theWorld Health Organization's List of Essential Medicines in 2019.[7][8] It is no longer marketed in the United States.[3]
Kanamycin is indicated for short-term treatment of bacterial infections caused by one or more of the following pathogens:E. coli,Proteus species (both indole-positive and indole-negative),Enterobacter aerogenes,Klebsiella pneumoniae,Serratia marcescens, andAcinetobacter species. In cases of serious infection when the causative organism is unknown, Kanamycin injection in conjunction with apenicillin- orcephalosporin-type drug may be given initially before obtaining results of susceptibility testing.[citation needed]
Kanamycin does not treat viral infections.[9]
Kanamycin ispregnancy category D in the United States.[9]
Kanamycin enters breast milk in small amounts. The manufacturer therefore advises that people should either stop breastfeeding or kanamycin. TheAmerican Academy of Pediatrics considers kanamycin okay in breastfeeding.[10]
Kanamycin should be used with caution in newborns due to the risk of increased drug concentration resulting from immature kidney function.[9]
Seriousside effects includeringing in the ears or loss of hearing,toxicity to kidneys, andallergic reactions to thedrug.[11]Ototoxicity is a common quality among aminoglycosides, and its rate of incidence in kanamycin is around 3-10%.[12]
Other side effects include:[9]
Gastrointestinal effects
Musculoskeletal effects
Neurologic effects
Metabolic effects
Kanamycin works by interfering with protein synthesis. It binds to the30S subunit 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.[13]
Bacterial resistance to kanamycin is a serious and increasing phenomenon, which is very concerning for its use in treatingmultidrug-resistant tuberculosis and other multidrug-resistantGram-negative bacterial infections. This is due in part to possible cross-resistance between kanamycin and other aminoglycosides, such asamikacin,capreomycin, andgentamicin.[14] Resistance to these aminoglycosides is due to mutations in the16S rRNA gene (rrs) within the 30S subunit that stops the antibacterial from binding tightly to the gene.[15] These mutations are most commonly identified through asingle-nucleotide variant at the position 1401.[16]
Kanamycin is a mixture of three main components: kanamycin A, B, and C. Kanamycin A is the major component in kanamycin.[17] The effects of these components do not appear to be widely studied as individual compounds when used against prokaryotic and eukaryotic cells.[citation needed]The IUPAC name of Kanamycin A is O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→6)-O-[6-deoxy-6-amino-α-D-glucopyranosyl-(1→4)]-2-deoxy-D-streptamine.
While the main product produced byStreptomyces kanamyceticus is kanamycin A, additional products are also produced, including kanamycin B, kanamycin C, kanamycin D and kanamycin X.[18]
The kanamycin biosynthetic pathway can be divided into two parts. The first part is common to several aminoglycoside antibiotics, such asbutirosin andneomycin. In it a unique aminocyclitol, 2-deoxystreptamine, is biosynthesized fromD-glucopyranose 6-phosphate 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-D-glucosamine and UDP-α-D-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.[19]
Kanamycin is used in molecular biology as a selective agent most commonly to isolatebacteria (e.g.,E. coli) which have taken up genes (e.g., ofplasmids) coupled to a gene coding for kanamycin resistance (primarily Neomycin phosphotransferase II [NPT II/Neo]). Bacteria that have beentransformed with a plasmid containing the kanamycin resistance gene are plated on kanamycin (50-100 μg/mL) containingagar plates or are grown in media containing kanamycin (50-100 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 mg/mL).[citation needed]
At least one such gene,Atwbc19[20] is native to a plant species, of comparatively large size and its coded protein acts in a manner which decreases the possibility ofhorizontal gene transfer from the plant to bacteria; it may be incapable of giving resistance to bacteria even if gene transfer occurs.[citation needed]
The selection marker kanMX is a hybrid gene consisting of a bacterial aminoglycoside phosphotransferase (kanr fromtransposon Tn903) under control of the strong TEFpromoter fromAshbya gossypii.[21][22]
Mammalian cells, yeast, and othereukaryotes acquire resistance togeneticin (= G418, an aminoglycoside antibiotic similar to kanamycin) when transformed with a kanMX marker. In yeast, the kanMX marker avoids the requirement ofauxotrophic markers. In addition, the kanMX marker rendersE. coli resistant to kanamycin. Inshuttle vectors the KanMXcassette 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 actualopen reading frame.[21][23]
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 metalnanoparticles 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.[24]
