Kanamycin A

Last updated

Kanamycin A
Kanamycin A.svg
Clinical data
Other namesK/KAN/HLK/KM [1]
AHFS/Drugs.com Monograph
Pregnancy
category
  • D
Routes of
administration 		By mouth, intravenous, intramuscular
ATC code
Pharmacokinetic data
Bioavailability very low after by mouth delivery
Metabolism Unknown
Elimination half-life 2 hours 30 minutes
Excretion Urine (as unchanged drug)
Identifiers
  • 2-(aminomethyl)- 6-[4,6-diamino-3- [4-amino-3,5-dihydroxy-6-(hydroxymethyl) tetrahydropyran-2-yl]oxy- 2-hydroxy- cyclohexoxy]- tetrahydropyran- 3,4,5-triol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.374 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C18H36N4O11
Molar mass 484.503 g·mol−1
3D model (JSmol)
  • O([C@@H]2[C@@H](O)[C@H](O[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O)[C@@H](N)C[C@H]2N)[C@H]3O[C@@H]([C@@H](O)[C@H](N)[C@H]3O)CO
  • InChI=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 Yes check.svgY
  • Key:SBUJHOSQTJFQJX-NOAMYHISSA-N Yes check.svgY
   (verify)

Kanamycin A, [2] often referred to simply as kanamycin, is an antibiotic used to treat severe bacterial infections and tuberculosis. [3] It is not a first line treatment. [3] It is used by mouth, injection into a vein, or injection 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 in viral infections. [3]

Contents

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 during breastfeeding. [4] Kanamycin is in the aminoglycoside 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 by Hamao Umezawa from the bacterium Streptomyces kanamyceticus . [3] [6] It was removed from the World Health Organization's List of Essential Medicines in 2019. [7] [8] It is no longer marketed in the United States. [3]

Medical uses

Spectrum of activity

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 , and Acinetobacter species. In cases of serious infection when the causative organism is unknown, Kanamycin injection in conjunction with a penicillin- or cephalosporin-type drug may be given initially before obtaining results of susceptibility testing.[ citation needed ]

Kanamycin does not treat viral infections. [9]

Pregnancy and breastfeeding

Kanamycin is pregnancy 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. The American Academy of Pediatrics considers kanamycin okay in breastfeeding. [10]

Children

Kanamycin should be used with caution in newborns due to the risk of increased drug concentration resulting from immature kidney function. [9]

Side effects

Serious side effects include ringing in the ears or loss of hearing, toxicity to kidneys, and allergic reactions to the drug. [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

Mechanism

Kanamycin works by interfering with protein synthesis. It binds to the 30S 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

Bacterial resistance to kanamycin is a serious and increasing phenomenon, which is very concerning for its use in treating multidrug-resistant tuberculosis and other multidrug-resistant gram-negative bacterial infections. This is due in part to possible cross-resistance between kanamycin and other aminoglycosides, such as amikacin, capreomycin, and gentamicin. [14] Resistance to these aminoglycosides is due to mutations in the 16S 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 a single-nucleotide variant at the position 1401. [16]

Composition

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 ]

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. [18]

The kanamycin biosynthetic pathway can be divided into two parts. The first part is common to several aminoglycoside antibiotics, such as butirosin and neomycin. In it a unique aminocyclitol, 2-deoxystreptamine, is biosynthesized from D-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]

Use in research

Kanamycin is used in molecular biology as a selective agent most commonly to isolate bacteria (e.g., E. coli ) which have taken up genes (e.g., of plasmids) coupled to a gene coding for kanamycin resistance (primarily Neomycin phosphotransferase II [NPT II/Neo]). Bacteria that have been transformed with a plasmid containing the kanamycin resistance gene are plated on kanamycin (50-100 μg/mL) containing agar 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 of horizontal gene transfer from the plant to bacteria; it may be incapable of giving resistance to bacteria even if gene transfer occurs.[ citation needed ]

KanMX marker

The selection marker kanMX is a hybrid gene consisting of a bacterial aminoglycoside phosphotransferase (kanr from transposon Tn903) under control of the strong TEF promoter from Ashbya gossypii . [21] [22]

Mammalian cells, yeast, and other eukaryotes acquire resistance to geneticin (= G418, an aminoglycoside antibiotic similar to kanamycin) when transformed with a kanMX marker. In yeast, the kanMX marker avoids the requirement of auxotrophic markers. In addition, the kanMX marker renders E. coli resistant to kanamycin. In shuttle vectors the KanMX cassette 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 open reading frame. [21] [23]

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 nanoparticles 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]

Related Research Articles

<span class="mw-page-title-main">Antibiotic</span> Antimicrobial substance active against bacteria

An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the ones which cause the common cold or influenza. Drugs which inhibit growth of viruses are termed antiviral drugs or antivirals. Antibiotics are also not effective against fungi. Drugs which inhibit growth of fungi are called antifungal drugs.

<span class="mw-page-title-main">Ampicillin</span> Antibiotic

Ampicillin is an antibiotic belonging to the aminopenicillin class of the penicillin family. The drug is used to prevent and treat several bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B streptococcal infection in newborns. It is used by mouth, by injection into a muscle, or intravenously.

<span class="mw-page-title-main">Antimicrobial resistance</span> Resistance of microbes to drugs directed against them

Antimicrobial resistance occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria, viruses, protozoa, and fungi. Together, these adaptations fall under the AMR umbrella, posing significant challenges to healthcare worldwide. Misuse and improper management of antimicrobials are primary drivers of this resistance, though it can also occur naturally through genetic mutations and the spread of resistant genes.

<span class="mw-page-title-main">Vancomycin</span> Antibiotic medication

Vancomycin is a glycopeptide antibiotic medication used to treat certain bacterial infections. It is administered intravenously to treat complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant Staphylococcus aureus. Blood levels may be measured to determine the correct dose. Vancomycin is also taken orally to treat Clostridioides difficile infections. When taken orally, it is poorly absorbed.

<span class="mw-page-title-main">Drug resistance</span> Pathogen resistance to medications

Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is, resistance has evolved. Antimicrobial resistance and antineoplastic resistance challenge clinical care and drive research. When an organism is resistant to more than one drug, it is said to be multidrug-resistant.

<span class="mw-page-title-main">Streptomycin</span> Aminoglycoside antibiotic

Streptomycin is an antibiotic medication used to treat a number of bacterial infections, including tuberculosis, Mycobacterium avium complex, endocarditis, brucellosis, Burkholderia infection, plague, tularemia, and rat bite fever. For active tuberculosis it is often given together with isoniazid, rifampicin, and pyrazinamide. It is administered by injection into a vein or muscle.

<span class="mw-page-title-main">Neomycin</span> Type of antibiotic

Neomycin is an aminoglycoside antibiotic that displays bactericidal activity against Gram-negative aerobic bacilli and some anaerobic bacilli where resistance has not yet arisen. It is generally not effective against Gram-positive bacilli and anaerobic Gram-negative bacilli. Neomycin comes in oral and topical formulations, including creams, ointments, and eyedrops. Neomycin belongs to the aminoglycoside class of antibiotics that contain two or more amino sugars connected by glycosidic bonds.

<span class="mw-page-title-main">Gentamicin</span> Antibiotic medication

Gentamicin is an aminoglycoside antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among others. It is not effective for gonorrhea or chlamydia infections. It can be given intravenously, by intramuscular injection, or topically. Topical formulations may be used in burns or for infections of the outside of the eye. It is often only used for two days until bacterial cultures determine what specific antibiotics the infection is sensitive to. The dose required should be monitored by blood testing.

<span class="mw-page-title-main">Aminoglycoside</span> Antibacterial drug

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer more generally to any organic molecule that contains amino sugar substructures. Aminoglycoside antibiotics display bactericidal activity against Gram-negative aerobes and some anaerobic bacilli where resistance has not yet arisen but generally not against Gram-positive and anaerobic Gram-negative bacteria.

<span class="mw-page-title-main">Clindamycin</span> Antibiotic

Clindamycin is a lincosamide antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media, and endocarditis. It can also be used to treat acne, and some cases of methicillin-resistant Staphylococcus aureus (MRSA). In combination with quinine, it can be used to treat malaria. It is available by mouth, by injection into a vein, and as a cream or a gel to be applied to the skin or in the vagina.

<span class="mw-page-title-main">Aztreonam</span> Chemical compound

Aztreonam, sold under the brand name Azactam among others, is an antibiotic used primarily to treat infections caused by gram-negative bacteria such as Pseudomonas aeruginosa. This may include bone infections, endometritis, intra abdominal infections, pneumonia, urinary tract infections, and sepsis. It is given by intravenous or intramuscular injection or by inhalation.

<span class="mw-page-title-main">Amoxicillin/clavulanic acid</span> Combination antibiotic medication

Amoxicillin/clavulanic acid, also known as co-amoxiclav or amox-clav, sold under the brand name Augmentin, among others, is an antibiotic medication used for the treatment of a number of bacterial infections. It is a combination consisting of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor. It is specifically used for otitis media, streptococcal pharyngitis, pneumonia, cellulitis, urinary tract infections, and animal bites. It is taken by mouth or by injection into a vein.

<span class="mw-page-title-main">Meropenem</span> Broad-spectrum antibiotic

Meropenem, sold under the brand name Merrem among others, is an intravenous carbapenem antibiotic used to treat a variety of bacterial infections. Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax.

<span class="mw-page-title-main">Ceftazidime</span> Antibiotic medication

Ceftazidime, sold under the brand name Fortaz among others, is a third-generation cephalosporin antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for joint infections, meningitis, pneumonia, sepsis, urinary tract infections, malignant otitis externa, Pseudomonas aeruginosa infection, and vibrio infection. It is given by injection into a vein, muscle, or eye.

<span class="mw-page-title-main">Tigecycline</span> Chemical compound

Tigecycline, sold under the brand name Tygacil, is a tetracycline antibiotic medication for a number of bacterial infections. It is a glycylcycline class drug that is administered intravenously. It was developed in response to the growing rate of antibiotic resistant bacteria such as Staphylococcus aureus, Acinetobacter baumannii, and E. coli. As a tetracycline derivative antibiotic, its structural modifications has expanded its therapeutic activity to include Gram-positive and Gram-negative organisms, including those of multi-drug resistance.

<span class="mw-page-title-main">Amikacin</span> Antibiotic medication

Amikacin is an antibiotic medication used for a number of bacterial infections. This includes joint infections, intra-abdominal infections, meningitis, pneumonia, sepsis, and urinary tract infections. It is also used for the treatment of multidrug-resistant tuberculosis. It is used by injection into a vein using an IV or into a muscle.

<span class="mw-page-title-main">Fosfomycin</span> Chemical compound

Fosfomycin, sold under the brand name Monurol among others, is an antibiotic primarily used to treat lower urinary tract infections. It is not indicated for kidney infections. Occasionally it is used for prostate infections. It is generally taken by mouth.

<span class="mw-page-title-main">Arbekacin</span> Antibiotic

Arbekacin (INN) is a semisynthetic aminoglycoside antibiotic which was derived from kanamycin. It is primarily used for the treatment of infections caused by multi-resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Arbekacin was originally synthesized from dibekacin in 1973 by Hamao Umezawa and collaborators. It has been registered and marketed in Japan since 1990 under the trade name Habekacin. Arbekacin is no longer covered by patent and generic versions of the drug are also available under such trade names as Decontasin and Blubatosine.

Antibiotic synergy is one of three responses possible when two or more antibiotics are used simultaneously to treat an infection. In the synergistic response, the applied antibiotics work together to produce an effect more potent than if each antibiotic were applied singly. Compare to the additive effect, where the potency of an antibiotic combination is roughly equal to the combined potencies of each antibiotic singly, and antagonistic effect, where the potency of the combination is less than the combined potencies of each antibiotic.

<span class="mw-page-title-main">Cefiderocol</span> Antibiotic

Cefiderocol, sold under the brand name Fetroja among others, is an antibiotic used to treat complicated urinary tract infections when no other options are available. It is indicated for the treatment of multi-drug-resistant Gram-negative bacteria including Pseudomonas aeruginosa. It is given by injection into a vein.

References

  1. ↑ "Antibiotic abbreviations list" . Retrieved 22 June 2023.
  2. ↑ Elks J, Ganellin DR (1990). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 717–. doi:10.1007/BF00171763. S2CID   122125855.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 "Kanamycin Sulfate". The American Society of Health-System Pharmacists. Archived from the original on 10 September 2017. Retrieved 6 December 2016.
  4. ↑ "Kanamycin (Kantrex) Use During Pregnancy". www.drugs.com. Archived from the original on 20 December 2016. Retrieved 7 December 2016.
  5. ↑ Lounis N, Truffot-Pernot C, Grosset J (March 1977). "Which aminoglycoside or fluoroquinolone is more active against Mycobacterium tuberculosis in mice?". Antimicrobial Agents and Chemotherapy. 41 (3): 607–610. doi:10.1128/aac.41.3.607. PMID   9056001.
  6. ↑ Sneader W (2005). Drug Discovery: A History. John Wiley & Sons. p. 302. ISBN   9780471899792.
  7. ↑ World Health Organization (2019). 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. Geneva: World Health Organization. hdl: 10665/325773 . WHO/MVP/EMP/IAU/2019.05. License: CC BY-NC-SA 3.0 IGO.
  8. ↑ World Health Organization (2019). 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). Geneva: World Health Organization. hdl: 10665/330668 . ISBN   9789241210300. ISSN   0512-3054. WHO technical report series;1021.
  9. 1 2 3 4 "Kanamycin (By injection)". Archived from the original on 10 September 2017.
  10. ↑ Briggs G (2011). Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. Lippincott Williams & Wilkins. p. 787.
  11. ↑ Consumer Drug Information: Kanamycin, 2 April 2008, archived from the original on 3 May 2008, retrieved 4 May 2008
  12. ↑ Chan ED, Chatterjee D, Iseman MD, Heifets LB (2004). "Pyrazinamide, ethambutol, ethionamide, and aminoglycosides". In Rom WN, Garay SM (ed.). Tuberculosis (2 ed.). Lippincott Williams & Wilkins.
  13. ↑ "Kanamycin". DrugBank. 17 August 2016.
  14. ↑ Das DJ, Shankar A, Johnson JB, Thomas S (2020). "Critical insights into antibiotic resistance transferability in probiotic Lactobacillus". Nutrition. 69. doi:10.1016/j.nut.2019.110567.
  15. ↑ Jugheli L, Bzekalava N, de Rijk P, Fissette K, Portaels F, Rigouts L (2009). "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". Antimicrobial Agents and Chemotherapy. 53 (12): 5064–5068. doi:10.1128/AAC.00851-09. PMID   19752274.
  16. ↑ Ley SD, Pillay S, Streicher EM, van der Heijden YF, Sirgel F, Derendinger B, et al. (July 2021). "Melting the eis: Nondetection of Kanamycin Resistance Markers by Routine Diagnostic Tests and Identification of New eis Promoter Variants". Antimicrobial Agents and Chemotherapy. 65 (7). doi:10.1128/AAC.02502-20. PMID   33903113.
  17. ↑ "Kanamycin". PubChem. U.S. National Library of Medicine.
  18. ↑ "Kanamycin Sulfate, USP". TOKU-E. Retrieved 28 June 2024.
  19. ↑ "kanamycin biosynthesis pathway". MetaCyc. Retrieved 30 September 2014.
  20. ↑ "Horizontal Gene Transfer: Plant vs. Bacterial Genes for Antibiotic Resistance Scenario's—What's the Difference?". Isb.vt.edu. Archived from the original on 6 June 2013. Retrieved 24 June 2013.
  21. 1 2 Wach A, Brachat A, Pöhlmann R, Philippsen P (December 1994). "New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae". Yeast. 10 (13): 1793–1808. doi:10.1002/yea.320101310. PMID   7747518. S2CID   25158247.
  22. ↑ Steiner S, Philippsen P (February 1994). "Sequence and promoter analysis of the highly expressed TEF gene of the filamentous fungus Ashbya gossypii". Molecular & General Genetics. 242 (3): 263–271. doi:10.1007/BF00280415. PMID   8107673. S2CID   19928246.
  23. ↑ Wach A (March 1996). "PCR-synthesis of marker cassettes with long flanking homology regions for gene disruptions in S. cerevisiae". Yeast. 12 (3): 259–265. doi:10.1002/(SICI)1097-0061(19960315)12:3<259::AID-YEA901>3.0.CO;2-C. PMID   8904338. S2CID   10450123.
  24. ↑ Payne JN, Waghwani HK, Connor MG, Hamilton W, Tockstein S, Moolani H, et al. (May 2016). "Novel Synthesis of Kanamycin Conjugated Gold Nanoparticles with Potent Antibacterial Activity". Frontiers in Microbiology. 7: 607. doi: 10.3389/fmicb.2016.00607 . PMC   4908860 . PMID   27330535.
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