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Gentamicin, sold under the brandname Garamycin among other, is an antibiotic used to treat many 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 injection into a muscle, or topically. Topical formulations may be used in burns or for infections of the outside of the eye. In the developed world it is often only used for two days until bacterial cultures determine what antibiotics the infection is sensitive to. The dose required should be monitored by blood testing.

Gentamicin can cause inner ear problems and kidney problems. The inner ear problems can include problems with balance and problems with hearing. These problems may be permanent. If used during pregnancy it can cause harm to the baby. It appears to be safe for use during breastfeeding. Gentamicin is a type of aminoglycoside. It works by stopping the bacteria from making protein which typically kills the bacteria.

Gentamicin was discovered in 1963. It is made from the bacteria Micromonospora purpurea. Gentamicin is on the World Health Organization's List of Essential Medicines, the most important medication needed in a basic health system. It is available as a generic medication. It wholesale cost is between 0.05 and 0.58 USD per day.

Medical uses
Active against a wide range of bacterial infections, mostly Gram-negative bacteria including Pseudomonas, Proteus, Serratia, and the Gram-positive Staphylococcus.

Gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila bacterial infections (because of the risk of the person going into shock from lipid A endotoxin found in certain Gram-negative organisms). Gentamicin is also useful against Yersinia pestis, its relatives, and Francisella tularensis (the organism responsible for tularemia seen often in hunters and/or trappers).

Some Enterobacteriaceae, Pseudomonas spp., enterococci, Staphylococcus aureus and other staphylococci are resistant to gentamicin sulfate, to varying degrees.

Side effects
Side effects of gentamicin toxicity vary between people. Side effects may become apparent shortly after or up to months after gentamicin is administered. Symptoms of gentamicin toxicity include: Gentamicin is nephrotoxic. Risk factors for aminoglycoside nephrotoxicity include patient factors such as: Treatment factors can also affect toxicity. Important factors such as dose, frequency, levels and duration of therapy can affect level of toxicity.
 * Balance difficulty
 * Bouncing, unsteady vision
 * Ringing in the ears (tinnitus)
 * Difficulty multi-tasking, particularly when standing
 * increased age
 * reduced renal function
 * pregnancy
 * hypothyroidism
 * hepatic dysfunction
 * volume depletion
 * metabolic acidosis
 * concurrent use of other drugs: vancomycin, NSAIDs, cisplatin, cyclosporin, cephalosporin, diuretics
 * Concurrent use of iodinated contrast agents

Psychiatric symptoms related to gentamicin can occur. These include anorexia, confusion, depression, disorientation and visual hallucinations.

A number of factors and determinants should be taken into account when using gentamicin, including differentiation between empirical and directed therapy which will affect dosage and treatment period. Many medical practitioners freely administer gentamicin as an antibiotic without advising people of the severe and permanent potential ramifications of its use. Gentamicin is a low-cost medicine when compared with alternatives, and is typically US$3–6 per dosage less than alternatives.

Inner ear
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 DNA encoding the 12S ribosomal RNA (m.1555 A>G), that allows the gentamicin to affect their cells. The cells of the ear are particularly sensitive to this, sometimes causing complete hearing loss. However, gentamicin is sometimes used intentionally for this purpose in severe Ménière's disease, to disable the vestibular apparatus. These side effects are most common when the drug is administered via drops directly to the ear.

Kidneys
Prevention of nephrotoxicity includes judicious use of IV fluids to correct and avoid volume depletion, correction of hypokalemia and hypomagnesemia. Once daily dosing has been shown to be less toxic than multiple daily doses. Gentamicin is usually dosed by ideal body weight. Various formulae exist for calculating gentamicin dosage. Trough and peak serum levels of gentamicin are monitored during treatment to individualize therapy and prevent excess exposure.

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.

Mechanism of action
Gentamicin is a bactericidal antibiotic that works by irreversibly binding the 30S subunit of the bacterial ribosome, interrupting protein synthesis. This mechanism of action is similar to other aminoglycosides. Gentamicin is a bactericidal antibiotic.

Components
Gentamicin is composed of a number of related gentamicin components and fractions which have varying degrees of antimicrobial potency. The main components of gentamicin include members of the gentamicin C complex: gentamicin C1, gentamicin C1a, and gentamicin C2 which compose approximately 80% of gentamicin and have been found to have the highest antibacterial activity. Gentamicin A, B, X, and a few others make up the remaining 20% of gentamicin and have lower antibiotic activity than the gentamicin C complex. The exact composition of a given sample or lot of gentamicin is not well defined, and the level of gentamicin C components or other components in gentamicin may differ from lot-to-lot depending on the gentamicin manufacturer or manufacturing process. Because of this lot-to-lot variability, it can be difficult to study various properties of gentamicin including pharmacokinetics and microorganism susceptibility if there is an unknown combination of chemically related but different compounds.

History


Gentamicin is produced by the fermentation of Micromonospora purpurea. It was discovered in 1963 by Weinstein, Wagman et al. at Schering Corporation in Bloomfield, N.J. working with source material (soil samples) provided by Rico Woyciesjes. Subsequently it was purified and the structures of its three components determined by Cooper, et al., also at the Schering Corporation. It was initially used as a topical treatment for burns at the Atlanta and San Antonio burn units and was introduced into IV usage in 1971. It remains a mainstay for use in sepsis.

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) generally have their spellings ending in ~micin and not in ~mycin.

Research
Gentamicin is also used in molecular biology research as an antibacterial agent in tissue and cell culture, to prevent contamination of sterile cultures. Gentamicin is one of the few heat-stable antibiotics that remain active even after autoclaving, which makes it particularly useful in the preparation of some microbiological growth media.