Amikacin is an antibiotic medication used for a number of bacterial infections.[ It is also used for the treatment of multidrug-resistant tuberculosis.][
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Amikacin, like other aminoglycoside, 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.][
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Amikacin was patented in 1971, and came into commercial use in 1976.[
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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.
It is often used in the following situations:
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Bronchiectasis
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Bone and joint infections
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Granulocytopenia, when combined with ticarcillin, in people with cancer
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Intra-abdominal infections (such as peritonitis) as an adjunct to other medicines, like clindamycin, metronidazole, piperacillin/tazobactam, or ampicillin/sulbactam
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Meningitis:
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for meningitis by E. coli, as an adjunct to imipenem
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for meningitis caused by Pseudomonas, as an adjunct to meropenem
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for meningitis caused by Acinetobacter, as an adjunct to imipenem or colistin
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for neonatal meningitis caused by Streptococcus agalactiae or Listeria monocytogenes, as an adjunct to ampicillin
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for neonatal meningitis caused by Gram negative bacteria such as E. coli, as adjunct to a 3rd-generation cephalosporin
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Mycobacterial infections, including as a second-line agent for active tuberculosis.
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Rhodococcus equi, which causes an infection resembling tuberculosis
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Respiratory tract infections, including as an adjunct to or carbapenem for hospital-acquired pneumonia
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Sepsis, including that in neonates,
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Skin and suture-site infections
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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.
Available forms
A liposome inhalation suspension is also available and approved to treat Mycobacterium avium complex (MAC) in the United States,[ ]
Amikacin liposome inhalation suspension is the first drug approved under the US limited population pathway for antibacterial and antifungal drugs (LPAD pathway).
The safety and efficacy of amikacin liposome inhalation suspension, an inhaled treatment taken through a nebulizer, was demonstrated in a randomized, controlled clinical trial where patients were assigned to one of two treatment groups.
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 3.7 hours in the fetus.][
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In general, amikacin should be avoided in infants.
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.[
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Adverse effects
Side-effects of amikacin are similar to those of other aminoglycosides. Nephrotoxicity and ototoxicity (which can lead to hearing loss) are the most important effects, occurring in 1–10% of users.
Amikacin can cause neurotoxicity if used at a higher dose or for longer than recommended. The resulting effects of neurotoxicity include vertigo, numbness, Paresthesia of the skin (paresthesia), muscle Convulsion, and seizures.
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;
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, drug fever, , 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.
The amikacin liposome inhalation suspension prescribing information includes a boxed warning regarding the increased risk of respiratory conditions including hypersensitivity pneumonitis (inflamed lungs), bronchospasm (tightening of the airway), exacerbation of underlying lung disease and hemoptysis (spitting up blood) that have led to hospitalizations in some cases.
Contraindications
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),
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.
Interactions
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 effect 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,
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.
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.
Pharmacology
Mechanism of action
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 correctly.
At normal doses, amikacin-sensitive bacteria respond within 24–48 hours.
Resistance
Amikacin evades attacks by all antibiotic-inactivating enzymes that are responsible for antibiotic resistance in bacteria, except for aminoacetyltransferase and nucleotidyltransferase.
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 tuberculosis, 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.
Pharmacokinetics
Amikacin is not absorbed orally and thus must be administered parenterally. It reaches peak serum concentrations in 0.5–2 hours when administered intramuscularly. Less than 11% of the amikacin actually binds to plasma proteins. It is distributed into the heart, gallbladder, lungs, and , 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.
While the half-life of amikacin is normally two hours, it is 50 hours in those with end-stage renal disease.
The majority (95%) of amikacin from an intramuscular or intravenous dose is secreted unchanged via glomerular filtration and into the urine within 24 hours.
Chemistry
Amikacin is derived from kanamycin A:
Veterinary uses
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,
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.
In horses, amikacin is FDA-approved for uterine infections (such as endometriosis and pyometra) when caused by susceptible bacteria.
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 Hemodialysis or peritoneal dialysis, which reduce serum concentrations of amikacin, and/or penicillins, some of which can form complexes with amikacin that deactivate it.
