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 accommo ...

) is a semisynthetic aminoglycoside

antibiotic 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 ...

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 Dibekacin (3',4'-dideoxykanamycin B) is an aminoglycoside antibiotic. It is a semisynthetic derivative of kanamycin developed by Hamao Umezawa and collaborators for Meiji Seika is a Japanese snack food company. It is the trade name of a pharm ...

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.

Pharmacology

Arbekacin is approved for the treatment of

pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...

and

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

caused by methicillin-resistant ''Staphylococcus aureus'' (MRSA). Because of its synergistic effect with

beta-lactams A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is ...

, arbekacin also holds promise as a treatment for multidrug-resistant Gram-negative bacterial infections such as multidrug-resistant ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerugi ...

'' and '' Acinetobacter baumannii''.

Pharmacodynamics

Aminoglycosides such as arbekacin work by binding to the bacterial 30S ribosomal subunit, causing misreading of

tRNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...

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 oxygenate ...

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 The prokaryotic small ribosomal subunit, or 30 S subunit, is the smaller subunit of the 70S ribosome found in prokaryotes. It is a complex of the 16S ribosomal RNA (rRNA) and 19 proteins. This complex is implicated in the binding of transfer RN ...

. Specifically, arbekacin binds to four nucleotides of

16S rRNA 16S rRNA may refer to: * 16S ribosomal RNA 16 S ribosomal RNA (or 16 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 g ...

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

. 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 A polyribosome (or polysome or ergosome) is a group of ribosomes bound to an Messenger RNA, mRNA molecule like “beads” on a “thread”. It consists of a complex of an mRNA molecule and two or more ribosomes that act to translation (biology) ...

into nonfunctional monosomes.

Absorption

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

parenteral A route of administration in pharmacology and toxicology 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 and nephrotoxicity are the most serious

adverse Adverse or adverse interest, in law, is anything that functions contrary to a party (law), party's interest. This word should not be confused with wikt:averse, averse. Adverse possession In property law, adverse possession refers to an interest i ...

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 have l ...

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 nutrie ...

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