gentamicin

Gentamicin
Systematic (IUPAC) name
(3R,4R,5R)-2-{[(1S,2S,3R,4S,6R)-4,6- diamino-3-{[(2R,3R,6S)- 3-amino-6-[(1R)- 1-(methylamino)ethyl]oxan-2-yl]oxy}- 2-hydroxycyclohexyl]oxy}-5-methyl- 4-(methylamino)oxane-3,5-diol
Identifiers
CAS number	1403-66-3
ATC code	D06AX07 J01GB03 S01AA11 S02AA14 S03AA06 QA07AA91 QG01AA91 QG51AA04 QJ51GB03
PubChem	3467
DrugBank	APRD00214
Chemical data
Formula	C21H43N5O7
Mol. mass	477.596 g/mol
Pharmacokinetic data
Bioavailability	limited oral bioavailability
Protein binding	0-10%
Metabolism	?
Half life	2 hrs
Excretion	renal
Therapeutic considerations
Pregnancy cat.	D
Legal status
Routes	IV, IM, topical

Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative bacteria. However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila bacterial infections (because of the risk of the patient going into shock from lipid A endotoxin found in certain gram negative organisms).

It is synthesized by Micromonospora, a genus of Gram-positive bacteria widely present in the environment (water and soil). To highlight their specific biological origins, gentamicin and other related antibiotics produced by this genus (verdamicin, mutamicin, sisomicin, netilmicin, retymicin) have generally their spellings ending in ~micin and not in ~mycin. Gentamicin is a bactericidal antibiotic that works by binding the 30S subunit of the bacterial ribosome, interrupting protein synthesis.

Like all aminoglycosides, when gentamicin is given orally, it is not systemically active. This is because it is not absorbed to any appreciable extent from the small intestine. It appears to be completely eliminated unchanged in the urine. Urine must be collected for many days to recover all of a given dose because the drug binds avidly to certain tissues. It is administered intravenously, intramuscularly or topically to treat infections.

E. coli has shown some resistance to gentamicin, despite being Gram-negative.

Gentamicin is one of the few heat-stable antibiotics that remain active even after autoclaving, which makes it particularly useful in the preparation of certain microbiological growth media.

Treatment of susceptible bacterial infections, normally Gram-negative bacteria including Pseudomonas, Proteus, Serratia, and Gram-positive Staphylococcus.^[1]

Gentamicin is the only heat-stable antibiotic, hence its use during orthopaedic surgery when high temperatures are required for the setting of cements (e.g. hip replacements).^{[citation needed]}

Side effects

It has been suggested that Gentamicin toxicity be merged into this article or section. (Discuss)

All aminoglycosides are toxic to the sensory cells of the ear, but they vary greatly in their relative effects on hearing versus balance. Gentamicin is a vestibulotoxin, and can cause permanent loss of equilibrioception, caused by damage to the vestibular apparatus of the inner ear, usually if taken at high doses or for prolonged periods of time, but there are well documented cases in which gentamicin completely destroyed the vestibular apparatus after three to five days. A small number of affected individuals have a normally harmless mutation in their mitochondrial RNA, that allows the gentamicin to affect their cells. The cells of the ear are particularly sensitive to this. Gentamicin is sometimes used intentionally for this purpose in severe Ménière's disease, to disable the vestibular apparatus.

Gentamicin can also be highly nephrotoxic, particularly if multiple doses accumulate over a course of treatment. For this reason gentamicin is usually dosed by body weight. Various formulae exist for calculating gentamicin dosage. Also trough and peak serum levels of gentamicin are monitored during treatment, generally before and after the third dose is infused.

Gentamicin, like other aminoglycosides, causes nephrotoxicity by inhibiting protein synthesis in renal cells. This mechanism specifically causes necrosis of cells in the proximal tubule, resulting in acute tubular necrosis which can lead to acute renal failure.^[2]

Side effects of gentamicin toxicity vary from patient to patient. Side effects may become apparent shortly after or up to months after gentamicin is administered. Symptoms of gentamicin toxicity are not limited to:

• Balance difficulty
• Bouncing, unsteady vision
• Ringing in the ears
• Difficulty multi-tasking, particularly standing up

Immediate professional help should be sought if any of these symptoms or others appear after administration of aminoglycosides. General medical practitioners should refer patients with such symptoms to an otolaryngologist, commonly known as an 'ear, nose, and throat doctor', for comprehensive tests.

Many medical practitioners freely administer gentamicin as an antibiotic without advising patients of the severe and permanent potential ramifications of its use. Gentamicin is well known to be a cheap, low cost yet old medicine as compared to modern alternatives, and is typically US$3-6 per dosage [avg] less than modern alternatives

Production and usage in research

Gentamicin is produced by a fermentation procedure. It was discovered by a Chinese microbiologist, Yue Wang. The majority of the world's gentamicin production takes place in China and South Korea; the last European producer is Lek, part of Sandoz group.

Gentamicin has been used since the early 1980s in microbiological research. The gentamicin protection assay enables researchers to quantify the ability of pathogenic bacteria to invade eukaryotic cells. It takes advantage of the fact that gentamicin is not able to penetrate eukaryotic cells.

References

• Complete Gentamicin Information at Drugs.com
• Wobblers.com is a well established Support Group for Gentamicin Victims