Gentamicin
Encyclopedia
Gentamicin is an aminoglycoside
antibiotic
, used to treat many types of bacteria
l infections, particularly those caused by Gram-negative
organisms. However, gentamicin is not used for Neisseria gonorrhoeae
, Neisseria meningitidis
or Legionella pneumophila
. Gentamicin is also ototoxic and nephrotoxic, with this toxicity remaining a major problem in clinical use.
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. 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 is administered intravenously
, intramuscularly
or topical
ly to treat infections. 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.
E. coli
has shown some resistance to gentamicin, despite being Gram-negative. Reluctance to use gentamicin for empirical therapy has led to increased use of alternative broad-spectrum antibiotics, which some experts suggest has led to the prevalence of antibiotic-resistant bacterial infections by Golden Staph
and other so-called "superbugs".
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. It is used during orthopaedic surgery when high temperatures are required for the setting of cements (e.g. hip replacements).
, 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 patient going into shock from lipid A endotoxin
found in certain Gram-negative organisms). Gentamicin is also useful against Yersinia pestis
and its relatives.
, 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 (m1555 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.
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
.
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 include:
Psychiatric symptoms related to gentamicin can occur. These include anorexia, confusion, depression, disorientation and visual hallucinations.
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.
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 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 less than modern alternatives.
Many people recover from gentamicin toxicity naturally over time if the drug is discontinued, but they recover slowly and usually incompletely. Sometimes the toxicity of gentamicin can still increase over months after the last dose. Upon cessation of gentamicin therapy symptoms such as tinnitus and imbalance may become less pronounced. Sensori-neural hearing loss caused by gentamicin toxicity is permanent however.
Aminoglycoside
An aminoglycoside is a molecule or a portion of a molecule composed of amino-modifiedsugars.Several aminoglycosides function as antibiotics that are effective against certain types of bacteria...
antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
, used to treat many types of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l infections, particularly those caused by Gram-negative
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
organisms. However, gentamicin is not used for Neisseria gonorrhoeae
Neisseria gonorrhoeae
Neisseria gonorrhoeae, also known as gonococci , or gonococcus , is a species of Gram-negative coffee bean-shaped diplococci bacteria responsible for the sexually transmitted infection gonorrhea.N...
, Neisseria meningitidis
Neisseria meningitidis
Neisseria meningitidis, often referred to as meningococcus, is a bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life threatening sepsis. N. meningitidis is a major cause of morbidity and mortality during childhood in industrialized countries...
or Legionella pneumophila
Legionella pneumophila
Legionella pneumophila is a thin, ærobic, pleomorphic, flagellated, non-spore forming, Gram-negative bacterium of the genus Legionella. L. pneumophila is the primary human pathogenic bacterium in this group and is the causative agent of legionellosis or Legionnaires' disease.-Characterization:L...
. Gentamicin is also ototoxic and nephrotoxic, with this toxicity remaining a major problem in clinical use.
It is synthesized by Micromonospora
Micromonospora
Micromonospora is a genus of bacteria of the family Micromonosporaceae. They are gram-positive, spore-forming, generally aerobic, and form a branched mycelium; they occur as saprotrophic forms in soil and water...
, 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
Verdamicin
Verdamicin is an aminoglycoside antibiotic produced by Micromonospora grisea....
, mutamicin, sisomicin
Sisomicin
Sisomicin is an aminoglycoside antibiotic....
, netilmicin
Netilmicin
Netilmicin is a member of the aminoglycoside family of antibiotics. These antibiotics have the ability to kill a wide variety of bacteria. Netilmicin is not absorbed from the gut and is therefore only given by injection or infusion...
, retymicin) generally have their spellings ending in ~micin and not in ~mycin. Gentamicin is a bactericidal antibiotic that works by binding the 30S
30S
30S is the smaller subunit of the 70S ribosome of prokaryotes. It is a complex of ribosomal RNA and ribonucleoproteins that functions in mRNA translation...
subunit of the bacterial ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
, 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
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
. It is administered intravenously
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
, intramuscularly
Intramuscular injection
Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...
or topical
Topical
In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, anus, throat, eyes and ears.Many topical medications are epicutaneous, meaning that they are applied directly to the skin...
ly to treat infections. 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.
E. coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
has shown some resistance to gentamicin, despite being Gram-negative. Reluctance to use gentamicin for empirical therapy has led to increased use of alternative broad-spectrum antibiotics, which some experts suggest has led to the prevalence of antibiotic-resistant bacterial infections by Golden Staph
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
and other so-called "superbugs".
Gentamicin is one of the few heat-stable antibiotics that remain active even after autoclaving
Autoclave
An autoclave is an instrument used to sterilize equipment and supplies by subjecting them to high pressure saturated steam at 121 °C for around 15–20 minutes depending on the size of the load and the contents. It was invented by Charles Chamberland in 1879, although a precursor known as the...
, which makes it particularly useful in the preparation of some microbiological growth media. It is used during orthopaedic surgery when high temperatures are required for the setting of cements (e.g. hip replacements).
Spectrum of activity
Active against a wide range of human bacterial infections, mostly Gram-negative bacteria including PseudomonasPseudomonas
Pseudomonas is a genus of gammaproteobacteria, belonging to the family Pseudomonadaceae containing 191 validly described species.Recently, 16S rRNA sequence analysis has redefined the taxonomy of many bacterial species. As a result, the genus Pseudomonas includes strains formerly classified in the...
, Proteus
Proteus (bacterium)
Proteus is a genus of Gram-negative Proteobacteria.-Clinical significance:Three species—P. vulgaris, P. mirabilis, and P. penneri—are opportunistic human pathogens. Proteus includes pathogens responsible for many human urinary tract infections. P. mirabilis causes wound and urinary...
, Serratia
Serratia
Serratia is a genus of Gram-negative, facultatively anaerobic, rod-shaped bacteria of the Enterobacteriaceae family. The most common species in the genus, S. marcescens, is normally the only pathogen and usually causes nosocomial infections. However, rare strains of S. plymuthica, S. liquefaciens,...
, and the Gram-positive Staphylococcus
Staphylococcus
Staphylococcus is a genus of Gram-positive bacteria. Under the microscope they appear round , and form in grape-like clusters....
. Gentamicin is not used for Neisseria gonorrhoeae
Neisseria gonorrhoeae
Neisseria gonorrhoeae, also known as gonococci , or gonococcus , is a species of Gram-negative coffee bean-shaped diplococci bacteria responsible for the sexually transmitted infection gonorrhea.N...
, Neisseria meningitidis
Neisseria meningitidis
Neisseria meningitidis, often referred to as meningococcus, is a bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life threatening sepsis. N. meningitidis is a major cause of morbidity and mortality during childhood in industrialized countries...
or Legionella pneumophila
Legionella pneumophila
Legionella pneumophila is a thin, ærobic, pleomorphic, flagellated, non-spore forming, Gram-negative bacterium of the genus Legionella. L. pneumophila is the primary human pathogenic bacterium in this group and is the causative agent of legionellosis or Legionnaires' disease.-Characterization:L...
bacterial infections (because of the risk of the patient going into shock from lipid A endotoxin
Endotoxin
Endotoxins are toxins associated with some Gram-negative bacteria. An "endotoxin" is a toxin that is a structural molecule of the bacteria that is recognized by the immune system.-Gram negative:...
found in certain Gram-negative organisms). Gentamicin is also useful against Yersinia pestis
Yersinia pestis
Yersinia pestis is a Gram-negative rod-shaped bacterium. It is a facultative anaerobe that can infect humans and other animals....
and its relatives.
Side effects
These 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 equilibrioceptionEquilibrioception
Equilibrioception or sense of balance is one of the physiological senses. It helps prevent humans and animals from falling over when walking or standing still. Balance is the result of a number of body systems working together: the eyes , ears and the body's sense of where it is in space ideally...
, 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 (m1555 A>G), that allows the gentamicin to affect their cells. The cells of the ear
Ear
The ear is the organ that detects sound. It not only receives sound, but also aids in balance and body position. The ear is part of the auditory system....
are particularly sensitive to this, sometimes causing complete hearing loss. However, gentamicin is sometimes used intentionally for this purpose in severe Ménière's disease
Ménière's disease
Ménière's disease is a disorder of the inner ear that can affect hearing and balance to a varying degree. It is characterized by episodes of vertigo and tinnitus and progressive hearing loss, usually in one ear. It is named after the French physician Prosper Ménière, who, in an article published...
, 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
Body weight
The term body weight is used in daily English speech as well as in the contexts of biological and medical sciences to describe the mass of an organism's body. Body weight is measured in kilograms throughout the world, although in some countries it is still measured in pounds or stones and pounds...
. 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
Nephrotoxicity
Nephrotoxicity is a poisonous effect of some substances, both toxic chemicals and medication, on the kidneys. There are various forms of toxicity. Nephrotoxicity should not be confused with the fact that some medications have a predominantly renal excretion and need their dose adjusted for the...
by inhibiting protein synthesis in renal cells. This mechanism specifically causes necrosis of cells in the proximal tubule
Proximal tubule
The proximal tubule is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle.-Structure and appearance:...
, resulting in acute tubular necrosis
Acute tubular necrosis
Acute tubular necrosis or is a medical condition involving the death of tubular cells that form the tubule that transports urine to the ureters while reabsorbing 99% of the water . Tubular cells continually replace themselves and if the cause of ATN is removed then recovery is likely...
which can lead to acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
.
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 include:
- Balance difficulty
- Bouncing, unsteady vision
- Ringing in the ears (tinnitusTinnitusTinnitus |ringing]]") is the perception of sound within the human ear in the absence of corresponding external sound.Tinnitus is not a disease, but a symptom that can result from a wide range of underlying causes: abnormally loud sounds in the ear canal for even the briefest period , ear...
) - Difficulty multi-tasking, particularly when standing
Psychiatric symptoms related to gentamicin can occur. These include anorexia, confusion, depression, disorientation and visual hallucinations.
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
Otolaryngology
Otolaryngology or ENT is the branch of medicine and surgery that specializes in the diagnosis and treatment of ear, nose, throat, and head and neck disorders....
, commonly known as an 'ear, nose, and throat doctor', for comprehensive tests.
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 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 less than modern alternatives.
Many people recover from gentamicin toxicity naturally over time if the drug is discontinued, but they recover slowly and usually incompletely. Sometimes the toxicity of gentamicin can still increase over months after the last dose. Upon cessation of gentamicin therapy symptoms such as tinnitus and imbalance may become less pronounced. Sensori-neural hearing loss caused by gentamicin toxicity is permanent however.