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amikacin antibiotic, amikacin
Amikacin is an antibiotic used for a number of bacterial infections This includes joint infections, intraabdominal infections, meningitis, pneumonia, sepsis, and urinary tract infections It is also used for the treatment of multidrug-resistant tuberculosis It is used either by injection into a vein or muscle

Amikacin, like other aminoglycoside antibiotics, can cause hearing loss, balance problems, and kidney problems Other side effects include paralysis, resulting in the inability to breathe If used during pregnancy it may cause permanent deafness in the baby Amikacin works by blocking the function of the bacteria's 30S ribosomal subunit, making it unable to produce proteins

Amikacin was patented in 1971 and came into commercial use in 1976 It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system The wholesale cost in the developing world is 1380 to 13050 USD for a month In the United States a typical course of treatment costs 25 to 50 USD It is made from kanamycin


  • 1 Medical uses
    • 11 Available forms
    • 12 Special populations
  • 2 Adverse effects
  • 3 Contraindications
  • 4 Interactions
  • 5 Pharmacology
    • 51 Mechanism of action
      • 511 Resistance
    • 52 Pharmacokinetics
  • 6 Chemistry
  • 7 Veterinary use
  • 8 References

Medical uses

Amikacin is most often used for treating severe infections with multidrug-resistant, aerobic Gram-negative bacteria, especially Pseudomonas, Acinetobacter, Enterobacter, E coli, Proteus, Klebsiella, and Serratia The only Gram-positive bacteria that amikacin strongly affects are Staphylococcus and Nocardia Amikacin can also be used to treat non-tubercular mycobacterial infections and tuberculosis if caused by sensitive strains when first-line drugs fail to control the infection It is rarely used alone

It is often used in the following situations:

  • Bronchiectasis
  • Bone and joint infections
  • Granulocytopenia, when combined with ticarcillin, in people with cancer
  • Intra-abdominal infections such as peritonitis as an adjunct to other medicines, like clindamycin, metronidazole, piperacillin/tazobactam, or ampicillin/sulbactam
  • Meningitis:
    • for meningitis by E coli, as an adjunct to imipenem
    • for meningitis caused by Pseudomonas, as an adjunct to meropenem
    • for meningitis caused by Acetobacter, as an adjunct to imipenem or colistin
    • for neonatal meningitis caused by Streptococcus agalactiae or Listeria monocytogenes, as an adjunct to ampicillin
    • for neonatal meningitis caused by Gram negative bacteria such as E coli, as adjunct to a 3rd-generation cephalosporin
  • Mycobacterial infections, including as a second-line agent for active tuberculosis It is also used for infections by Mycobacterium avium, M abcessus, M chelonae, and M fortuitum
  • Rhodococcus equi, which causes an infection resembling tuberculosis
  • Respiratory tract infections, including as an adjunct to beta-lactams or carbapenem for hospital-acquired pneumonia
  • Septicemia, including that in neonates, as an adjunct to beta-lactams or carbapenem
  • Skin and suture-site infections
  • Urinary tract infections that are caused by bacteria resistant to less toxic drugs often by Enterobacteriaceae or P aeruginosa

Amikacin may be combined with a beta-lactam antibiotic for empiric therapy for people with neutropenia and fever

Liposomal amikacin for inhalation is currently in late stage clinical trials for the treatment of respiratory diseases, such as cystic fibrosis, Pseudomonas aeruginosa, non-tubercular mycobacterial infections and bronchiectasis

Available forms

Amikacin may be administered once or twice a day and is usually given by the intravenous or intramuscular route, though it can be given via nebulization There is no oral form available, as amikacin is not absorbed orally In people with kidney failure, dosage must be adjusted according to the creatinine clearance, usually by reducing the dosing frequency In people with a CNS infection such as meningitis, amikacin can be given intrathecally by direct injection into the spine or intraventricularly by injection into the ventricles of brain

Special populations

Amikacin should be used in smaller doses in the elderly, who often have age-related decreases in kidney function, and children, whose kidneys are not fully developed yet It is considered pregnancy category D in both the United States and Australia, meaning they have a probability of harming the fetus Around 16% of amikacin crosses the placenta; while the half-life of amikacin in the mother is 2 hours, it is 37 hours in the fetus A pregnant woman taking amikacin with another aminoglycoside has a possibility of causing congenital deafness in her child While it is known to cross the placenta, amikacin is only partially secreted in breast milk

In general, amikacin should be avoided in infants Infants also tend to have a larger volume of distribution due to their higher concentration of extracellular fluid, where aminoglycosides reside

The elderly tend to have amikacin stay longer in their system; while the average clearance of amikacin in a 20-year-old is 6 L/hr, it is 3 L/hr in an 80-year-old

Clearance is even higher in people with cystic fibrosis

In people with muscular disorders such as myasthenia gravis or Parkinson's disease, amikacin's paralytic effect on neuromuscular junctions can worsen muscle weakness

Adverse effects

Side-effects of amikacin are similar to those of other aminoglycosides Kidney damage and ototoxicity which can lead to hearing loss are the most important effects, occurring in 1–10% of users The nephro- and ototoxicity are thought to be due to aminoglycosides' tendency to accumulate in the kidneys and inner ear

Diagram of the inner ear Amikacin causes damage to the cochlea and vestibules

Amikacin can cause neurotoxicity if used at a higher dose or for longer than recommended The resulting effects of neurotoxicity include vertigo, numbness, tingling of the skin paresthesia, muscle twitching, and seizures Its toxic effect on the 8th cranial nerve causes ototoxicity, resulting in loss of balance and, more commonly, hearing loss Damage to the cochlea, caused by the forced apoptosis of the hair cells, leads to the loss of high-frequency hearing and happens before any clinical hearing loss can be detected Damage to the ear vestibules, most likely by creating excessive oxidative free radicals It does so in a time-dependent rather than dose-dependent manner, meaning that risk can be minimized by reducing the duration of use

Amikacin causes nephrotoxicity damage to the kidneys, by acting on the proximal renal tubules It easily ionizes to a cation and binds to the anionic sites of the epithelial cells of the proximal tubule as part of receptor-mediated pinocytosis The concentration of amikacin in the renal cortex becomes ten times that of amikacin in the plasma; it then most likely interferes with the metabolism of phospholipids in the lysosomes, which causes lytic enzymes to leak into the cytoplasm Nephrotoxicity results in increased serum creatinine, blood urea nitrogen, red blood cells, and white blood cells, as well as albuminuria increased output of albumin in the urine, glycosuria excretion of glucose into the urine, decreased urine specific gravity, and oliguria decrease in overall urine output It can also cause urinary casts to appear The changes in renal tubular function also change the electrolyte levels and acid-base balance in the body, which can lead to hypokalemia and acidosis or alkalosis Nephrotoxicity is more common in those with pre-existing hypokalema, hypocalcemia, hypomagnesemia, acidosis, low glomerular filtration rate, diabetes mellitus, dehydration, fever, and sepsis, as well as those taking antiprostaglandins The toxicity usually reverts once the antibiotic course has been completed, and can be avoided altogether by less frequent dosing such as once every 24 hours rather than once every 8 hours

Amikacin can cause neuromuscular blockade including acute muscular paralysis and respiratory paralysis including apnea

Rare side effects occurring in fewer than 1% of users include allergic reactions, skin rash, fever, headaches, tremor, nausea and vomiting, eosinophilia, arthralgia, anemia, hypotension, and hypomagnesemia In intravitreous injections where amikacin is injected into the eye, macular infarction can cause permanent vision loss


Amikacin should be avoided in those who are sensitive to any aminoglycoside, as they are cross-allergenic that is, an allergy to one aminoglycoside also confers hypersensitivity to other aminoglycosides It should also be avoided in those sensitive to sulfite seen more among people with asthma, since most amikacin usually comes with sodium metabisulfite, which can cause an allergic reaction

In general, amikacin should not be used with or just before/after another drug that can cause neurotoxicity, ototoxicity, or nephrotoxicity Such drugs include other aminoglycosides; the antiviral acyclovir; the antifungal amphotericin B; the antibiotics bacitracin, capreomycin, colistin, polymyxin B, and vancomycin; and cisplatin, which is used in chemotherapy

Amikacin should not be used with neuromuscular blocking agents, as they can increase muscle weakness and paralysis


Though amikacin can be inactivated by other beta-lactams, though not to the extent as other aminoglycosides, and is still often used with penicillins a type of beta-lactam to create an additive effect against certain bacteria, and carbapenems, which can have a synergistic against some Gram-positive bacteria Another group of beta-lactams, the cephalosporins, can increase the nephrotoxicity of aminoglycoside as well as randomly elevating creatinine levels The antibiotics chloramphenicol, clindamycin, and tetracycline have been known to inactivate aminoglycosides in general by pharmacological antagonism

The effect of amikacin is increased when used with drugs derived from the botulinum toxin, anesthetics, neuromuscular blocking agents, or large doses of blood that contains citrate as an anticoagulant

Potent diuretics not only cause ototoxicity themselves, but they can also increase the concentration of amikacin in the serum and tissue, making the ototoxicity even more likely Quinidine also increases levels of amikacin in the body The NSAID indomethacin can increase serum aminoglycoside levels in premature infants Contrast mediums such as ioversol increases the nephrotoxicity and otoxicity caused by amikacin

Amikacin can decrease the effect certain vaccines, such as the live BCG vaccine used for tuberculosis, the cholera vaccine, and the live typhoid vaccine by acting as a pharmacological antagonist


Mechanism of action

The 30S subunit of the prokaryotic ribosome The orange represents the 16S rRNA, and the blue represents the various proteins attached

Amikacin irreversibly binds to 16S rRNA and the RNA-binding S12 protein of the 30S subunit of prokaryotic ribosome and inhibits protein synthesis by changing the ribosome's shape so that it cannot read the mRNA codons correctly It also interferes with the region that interacts with the wobble base of the tRNA anticodon It works in a concentration-dependent manner, and has better action in an alkaline environment

At normal doses, amikacin-sensitive bacteria respond within 24–48 hours


Amikacin evades attacks by all antibiotic-inactivating enzymes that are responsible for antibiotic resistance in bacteria, except for aminoacetyltransferase and nucleotidyltransferase This is accomplished by the L-hydroxyaminobuteroyl amide L-HABA moiety attached to N-1 compare to kanamycin, which simply has a hydrogen, which blocks the access and decreases the affinity of aminoglycoside-inactivating enzymes Amikacin ends up with only one site where these enzymes can attack, while gentamicin and tobramycin have six

Bacteria that are resistant to streptomycin and capreomycin are still susceptible to amikacin; bacteria that are resistant to kanamycin have varying susceptibility to amikacin Resistance to amikacin also confers resistance to kanamycin and capreomycin

Resistance to amikacin and kanamycin in Mycobacterium, the causative agent of tuberculosis, is due to a mutation in the rrs gene, which codes for the 16S rRNA Mutations such as these reduce the binding affinity of amikacin to the bacteria's ribosome Variations of aminoglycoside acetyltransferase AAC and aminoglycoside adenylyltransferase AAD also confer resistance:resistance in Pseudomonas aeruginosa is caused by AAC6'-IV, which also confers resistance to kanamycin, gentamicin, and tobramycin, and resistance in Staphylococcus aureus and S epidermidis is caused by AAD4',4, which also confers resistance to kanamycin, tobramycin, and apramycin Some strains of S aureus can also inactivate amikacin by phosphorylating it


Amikacin is not absorbed orally and thus must be administered parenterally It reaches peak serum concentrations in 05–2 hours when administered intramuscularly Less than 11% of the amikacin actually binds to plasma proteins It is distributed into the heart, gallbladder, lungs, and bones, as well as in bile, sputum, interstitial fluid, pleural fluid, and synovial fluids It is usually found at low concentrations in the cerebrospinal fluid, except when administered intraventricularly In infants, amikacin is normally found at 10–20% of plasma levels in the spinal fluid, but the amount reaches 50% in cases of meningitis It does not easily cross the blood-brain barrier or enter ocular tissue

While the half-life of amikacin is normally two hours, it is 50 hours in those with end-stage renal disease

The vast majority 95% of amikacin from an IM or IV dose is secreted unchanged via glomerular filtration and into the urine within 24 hours Factors that cause amikacin to be excreted via urine include its relatively low molecular weight, high water solubility, and unmetabolized state


Amikacin is derived from kanamycin A:

Veterinary use

While amikacin is only FDA-approved for use in dogs and for intrauterine infection in horses, it is one of the most common aminoglycosides used in veterinary medicine, and has been used in dogs, cats, guinea pigs, chinchillas, hamsters, rats, mice, prairie dogs, cattle, birds, snakes, turtles and tortoises, crocodilians, bullfrogs, and fish It is often used for respiratory infections in snakes, bacterial shell disease in turtles, and sinusitis in macaws It is generally contraindicated in rabbits and hares though it has still been used because it harms the balance of intestinal microflora

In dogs and cats, amikacin is commonly used as a topical antibiotic for ear infections and for corneal ulcers, especially those that are caused by Pseudomonas aeruginosa The ears are often cleaned before administering the medication, since pus and cellular debris lessen the activity of amikacin Amikacin is administered to the eye when prepared as an ophthalmic ointment or solution, or when injected subconjunctivally Amikacin in the eye can be accompanied by cephazolin Despite its use there amikacin and all aminoglycosides are toxic to intraocular structures

In horses, amikacin is FDA-approved for uterine infections such as endometriosis and pyometra when caused by susceptible bacteria It is also used in topical medication for the eyes and arthroscopic lavage; when combined with a cephalosporin, is used to treat subcutaneous infections that are caused by Staphylococcus For infections in the limbs or joints, it is often administered with a cephalosporin via limb perfusion directly into the limb or injected into the joint Amikacin is also injected into the joints with the anti-arthritic medication Adequan in order to prevent infection

Side effects in animals include nephrotoxicity, ototoxicity, and allergic reactions at IM injection sites Cats tend to be more sensitive to the vestibular damage caused by ototoxicity Less frequent side effects include neuromuscular blockade, facial edema, and peripheral neuropathy

The half-life in most animals is one to two hours

Treating overdoses of amikacin requires kidney dialysis or peritoneal dialysis, which reduce serum concentrations of amikacin, and/or penicillins, some of which can form complexes with amikacin that deactivate it


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