Arbekacin

Last updated
Arbekacin
Arbekacin structure.svg
Clinical data
Trade names Habekacin
AHFS/Drugs.com International Drug Names
Routes of
administration
Intramuscular, intravenous
Drug class Aminoglycoside antibiotic
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Metabolism minimal
Excretion Renal
Identifiers
  • (2S)-4-Amino-N-[(1R,2S,3S,4R,5S)-5-amino-4-[(2R,3R,6S)-3-amino-6-(aminomethyl)oxan-2-yl]oxy-2-[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
Formula C22H44N6O10
Molar mass 552.626 g·mol−1
3D model (JSmol)
  • C1C[C@H]([C@H](O[C@@H]1CN)O[C@@H]2[C@H](C[C@H]([C@@H]([C@H]2O)O[C@@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CO)O)N)O)NC(=O)[C@H](CCN)O)N)N
  • InChI=InChI=1S/C22H44N6O10/c23-4-3-12(30)20(34)28-11-5-10(26)18(37-21-9(25)2-1-8(6-24)35-21)17(33)19(11)38-22-16(32)14(27)15(31)13(7-29)36-22/h8-19,21-22,29-33H,1-7,23-27H2,(H,28,34)/t8-,9+,10-,11+,12-,13+,14-,15+,16+,17-,18+,19-,21+,22+/m0/s1 Yes check.svgY
  • Key:MKKYBZZTJQGVCD-XTCKQBCOSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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). [1] [2] Arbekacin was originally synthesized from dibekacin in 1973 by Hamao Umezawa and collaborators. [3] It has been registered and marketed in Japan since 1990 under the trade name Habekacin. [4] Arbekacin is no longer covered by patent and generic versions of the drug are also available under such trade names as Decontasin and Blubatosine.

Contents

Pharmacology

Arbekacin is approved for the treatment of pneumonia and sepsis caused by methicillin-resistant Staphylococcus aureus (MRSA). Because of its synergistic effect with beta-lactams, arbekacin also holds promise as a treatment for multidrug-resistant Gram-negative bacterial infections such as multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii . [5]

Pharmacodynamics

Aminoglycosides such as arbekacin work by binding to the bacterial 30S ribosomal subunit, causing misreading of tRNA which consequently, leaves the bacterium unable to synthesize proteins vital to its growth. Energy is needed for aminoglycoside uptake into the bacterial cell. Anaerobes have less energy available for this uptake, so aminoglycosides are less active against anaerobes.[ citation needed ]

Mechanism of action

Aminoglycosides such as arbekacin inhibit protein synthesis in susceptible bacteria by irreversibly binding to the bacterial 30S ribosomal subunit. Specifically, arbekacin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with the decoding site in the vicinity of nucleotide 1400 in the 16S rRNA component of the 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to misreading of mRNA, so incorrect amino acids are inserted into the polypeptide, leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.[ citation needed ]

Absorption

Aminoglycosides are not well absorbed from the gastrointestinal tract, so they are typically administered parenterally.[ citation needed ]

Toxicity

Ototoxicity and nephrotoxicity are the most serious adverse effects of aminoglycoside therapy and are more likely to occur in patients with a history of renal impairment or who are receiving other ototoxic and/or nephrotoxic drugs. Normal duration of intramuscular or intravenous aminoglycoside therapy is 7–10 days, though longer treatment is sometimes necessary. Toxicity is more likely to occur when aminoglycoside treatment is continued for longer than 10 days.[ citation needed ]

Related Research Articles

<i>Staphylococcus aureus</i> Species of gram-positive bacterium

Staphylococcus aureus is a gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe, meaning that it can grow without oxygen. Although S. aureus usually acts as a commensal of the human microbiota, it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. S. aureus is one of the leading pathogens for deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA). The bacterium is a worldwide problem in clinical medicine. Despite much research and development, no vaccine for S. aureus has been approved.

<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.

Methicillin-resistant <i>Staphylococcus aureus</i> Bacterium responsible for difficult-to-treat infections in humans

Methicillin-resistant Staphylococcus aureus (MRSA) is a group of gram-positive bacteria that are genetically distinct from other strains of Staphylococcus aureus. MRSA is responsible for several difficult-to-treat infections in humans. It caused more than 100,000 deaths worldwide attributable to antimicrobial resistance in 2019.

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

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

Methicillin (USAN), also known as meticillin (INN), is a narrow-spectrum β-lactam antibiotic of the penicillin class.

<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.

Vancomycin-resistant <i>Staphylococcus aureus</i> Antibiotica resistant bacteria

Vancomycin-resistant Staphylococcus aureus (VRSA) are strains of Staphylococcus aureus that have acquired resistance to the glycopeptide antibiotic vancomycin. Bacteria can acquire resistance genes either by random mutation or through the transfer of DNA from one bacterium to another. Resistance genes interfere with the normal antibiotic function and allow bacteria to grow in the presence of the antibiotic. Resistance in VRSA is conferred by the plasmid-mediated vanA gene and operon. Although VRSA infections are uncommon, VRSA is often resistant to other types of antibiotics and a potential threat to public health because treatment options are limited. VRSA is resistant to many of the standard drugs used to treat S. aureus infections. Furthermore, resistance can be transferred from one bacterium to another.

<span class="mw-page-title-main">Neomycin/polymyxin B/bacitracin</span> Antibiotic medication

Neomycin/polymyxin B/bacitracin, also known as triple antibiotic ointment, is an antibiotic medication used to reduce the risk of infections following minor skin injuries. It contains the three antibiotics neomycin, polymyxin B, and bacitracin. It is for topical use.

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Kanamycin A, often referred to simply as kanamycin, is an antibiotic used to treat severe bacterial infections and tuberculosis. It is not a first line treatment. It is used by mouth, injection into a vein, or injection into a muscle. Kanamycin is recommended for short-term use only, usually from 7 to 10 days. Since antibiotics only show activity against bacteria, it is ineffective in viral infections.

<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">Pristinamycin</span> Group of chemical compounds

Pristinamycin (INN), also spelled pristinamycine, is an antibiotic used primarily in the treatment of staphylococcal infections, and to a lesser extent streptococcal infections. It is a streptogramin group antibiotic, similar to virginiamycin, derived from the bacterium Streptomyces pristinaespiralis. It is marketed in Europe by Sanofi-Aventis under the trade name Pyostacine.

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

Dicloxacillin is a narrow-spectrum β-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible (non-resistant) Gram-positive bacteria. It is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most penicillins. Dicloxacillin is available under a variety of trade names including Diclocil (BMS).

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

Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.

<span class="mw-page-title-main">Dalbavancin</span> Antibiotic used to treat MRSA

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

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Kerry L. LaPlante is an American pharmacist, academic and researcher. She is the Dean at the University of Rhode Island College of Pharmacy. She is a Professor of Pharmacy and former department Chair of the Department of Pharmacy Practice at the University of Rhode Island, an adjunct professor of medicine at Brown University, an Infectious Diseases Pharmacotherapy Specialist, and the Director of the Rhode Island Infectious Diseases Fellowship and Research Programs at the Veterans Affairs Medical Center in Providence, Rhode Island.

References

  1. Inoue M, Nonoyama M, Okamoto R, Ida T (1994). "Antimicrobial activity of arbekacin, a new aminoglycoside antibiotic, against methicillin-resistant Staphylococcus aureus". Drugs Under Experimental and Clinical Research. 20 (6): 233–239. PMID   7758395.
  2. Cordeiro JC, Reis AO, Miranda EA, Sader HS (June 2001). "In vitro antimicrobial activity of the aminoglycoside arbekacin tested against oxacillin-resistant Staphylococcus aureus isolated in Brazilian hospitals". The Brazilian Journal of Infectious Diseases. 5 (3). The Arbekacin Study Group: 130–135. doi: 10.1590/s1413-86702001000300005 . PMID   11506776.
  3. Kondo S, Iinuma K, Yamamoto H, Maeda K, Umezawa H (July 1973). "Letter: Syntheses of 1-n-(S)-4-amino-2-hydroxybutyryl)-kanamycin B and -3', 4'-dideoxykanamycin B active against kanamycin-resistant bacteria". The Journal of Antibiotics. 26 (7): 412–415. doi: 10.7164/antibiotics.26.412 . PMID   4782059.
  4. Kobayashi Y, Uchida H, Kawakami Y (July 1995). "Arbekacin". International Journal of Antimicrobial Agents. 5 (4): 227–230. doi:10.1016/0924-8579(95)00014-Y. PMID   18611673.
  5. Matsumoto T (2014). "Arbekacin: another novel agent for treating infections due to methicillin-resistant Staphylococcus aureus and multidrug-resistant Gram-negative pathogens". Clinical Pharmacology. 6: 139–148. doi: 10.2147/CPAA.S44377 . PMC   4186621 . PMID   25298740.