Arbekacin (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

) is a semisynthetic

aminoglycoside 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 ...

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

which was derived from

kanamycin 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. Kanamy ...

. 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 was a Japanese scientist who discovered several antimicrobial agents and enzyme inhibitors. Umezawa was born in Obama City, Fukui Prefecture, as the second son in a family of seven children. After graduating from Musashi Junior and Senior High ...

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.

Pharmacology

Arbekacin is approved for the treatment of

pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...

and

sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...

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 bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...

l infections such as multidrug-resistant ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...

'' and ''

Acinetobacter baumannii ''Acinetobacter baumannii'' is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromis ...

''.

Pharmacodynamics

Aminoglycosides such as arbekacin work by binding to the bacterial 30S

ribosomal Ribosomes () are macromolecular machines, found within all cells, that perform biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA molecules to fo ...

subunit, causing misreading of

tRNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

which consequently, leaves the bacterium unable to synthesize proteins vital to its growth. Energy is needed for aminoglycoside uptake into the bacterial cell.

Anaerobes An anaerobic organism or anaerobe is any organism that does not require molecular oxygen for growth. It may react negatively or even die if free oxygen is present. In contrast, an aerobic organism (aerobe) is an organism that requires an oxygenat ...

have less energy available for this uptake, so aminoglycosides are less active against anaerobes.

Mechanism of action

Aminoglycosides such as arbekacin inhibit protein synthesis in susceptible bacteria by irreversibly binding to the bacterial

30S ribosomal subunit 3 (three) is a number, numeral and digit. It is the natural number following 2 and preceding 4, and is the smallest odd prime number and the only prime preceding a square number. It has religious and cultural significance in many societies ...

. Specifically, arbekacin binds to four nucleotides of

16S rRNA 16S ribosomal RNA (or 16Svedberg, S rRNA) is the RNA component of the 30S subunit of a prokaryotic ribosome (SSU rRNA). It binds to the Shine-Dalgarno sequence and provides most of the SSU structure. The genes coding for it are referred to as ...

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 Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

. This leads to misreading of

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

, so incorrect amino acids are inserted into the polypeptide, leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.

Absorption

Aminoglycosides are not well absorbed from the gastrointestinal tract, so they are typically administered

parenteral In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...

ly.

Toxicity

Ototoxicity Ototoxicity is the property of being toxic to the ear (''oto-''), specifically the cochlea or auditory nerve and sometimes the vestibular system, for example, as a side effect of a drug. The effects of ototoxicity can be reversible and tempora ...

and

nephrotoxicity Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. There are various forms, and some drugs may affect kidney function in more than one way. Nephrotoxin ...

are the most serious

adverse Adverse or adverse interest, in law, is anything that functions contrary to a party's interest. This word should not be confused with averse. The most common use of the term is "an interest, claim , or right that is against another’s interest ...

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 Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles hav ...

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

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.

References

{{AminoglycosideAntiBiotics Aminoglycoside antibiotics