Amikacin is an antibiotic medication used for a number of bacterial infections.
Pregnancy category AU: D
Routes of administration Intramuscular, intravenous, inhalation
Drug class Aminoglycoside
Pharmacokinetic data Bioavailability >90%
Protein binding 0–11%
Metabolism Mostly unmetabolized
Elimination half-life 2–3 hours
Excretion Kidney
Bacterial infections treated includes joint infections, intra-abdominal infections, meningitis, pneumonia, sepsis, and urinary tract infections.
It is also used for the treatment of multidrug-resistant tuberculosis.
Amikacin, like other aminoglycoside antibiotics, can cause hearing loss, balance problems, and kidney problems, paralysis, resulting in the inability to breathe.
If used during pregnancy it may cause permanent deafness in the baby.
It works by blocking the function of the bacteria’s 30S ribosomal subunit, making it unable to produce proteins.
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.
Gram-positive bacteria that amikacin strongly affects are Staphylococcus and Nocardia.
Amikacin can also be used to treat non-tubercular mycobacterial infections and tuberculosis when first-line drugs fail to control the infection.
Amikacin is rarely used alone.
It is often used in the following situations:
Bronchiectasis
Bone and joint infections
Granulocytopenia
Intra-abdominal infections
Meningitis
Mycobacterial infections, including as a second-line agent for active tuberculosis.
Respiratory tract infections, including as an adjunct to beta-lactams or carbapenem for hospital-acquired pneumonia
Sepsis, 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.
A liposome inhalation suspension is also available and approved to treat Mycobacterium avium complex (MAC).
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, having 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.
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, it is only partially secreted in breast milk.
Amikacin should be avoided in infants, as 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.
The average clearance of amikacin in a 20-year-old is 6 L/hr, it is 3 L/hr in an 80-year-old.
In people with muscular disorders such as myasthenia gravis or Parkinson’s disease, amikacin’s paralytic effect on neuromuscular junctions can worsen muscle weakness.
Side-effects of amikacin: Kidney damage and ototoxicity are the most important effects, occurring in 1–10% of users: nephro- and ototoxicity are thought to be due to aminoglycosides’ tendency to accumulate in the kidneys and inner ear.
Amikacin causes damage to the cochlea and vestibules.\
Amikacin can cause neurotoxicity if used at a higher dose or for prolonged periods.
Neurotoxicity include vertigo, numbness, 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, by creating excessive oxidative free radicals is time-dependent rather than dose-dependent manner, meaning that risk can be minimized by reducing the duration of use.
Amikacin causes nephrotoxicity by acting on the proximal renal tubules, as It 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 most likely interferes with the metabolism of phospholipids in the lysosomes, which causes lytic enzymes to leak into the cytoplasm.
Nephrotoxicity increases serum creatinine, blood urea nitrogen, increases red blood cells, and white blood cells in the urine as well as causes albuminuria, glycosuria, decreased urine specific gravity, oliguria, can also cause urinary casts to appear, and 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 hypokalemia, hypocalcemia, hypomagnesemia, acidosis, low glomerular filtration rate, diabetes mellitus, dehydration, fever, and sepsis, as well as those taking antiprostaglandins.
Nephrotoxicity usually reverts once the antibiotic course has been completed.
Nephrotoxicity 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 with acute muscular paralysis and respiratory paralysis.
Rare side effects include allergic reactions, skin rash, fever, headaches, tremor, nausea and vomiting, eosinophilia, arthralgia, anemia, hypotension, and hypomagnesemia.
In intravitreous injections macular infarction can cause permanent vision loss.
The amikacin liposome inhalation suspension has increased risk of respiratory conditions including hypersensitivity pneumonitis. bronchospasm, exacerbation of underlying lung disease and hemoptysis that have led to hospitalizations in some cases.
Amikacin liposome inhalation suspension can cause dysphonia, cough, ototoxicity, upper airway irritation, musculoskeletal pain, fatigue, diarrhea and nausea.
Contraindications: amikacin should be avoided in those who are sensitive to any aminoglycoside, as they are cross-allergenic.
A Kachin should also be avoided in those sensitive to sulfite.
Amikacin should not be used with or just before/after another drug that can cause neurotoxicity, ototoxicity, or nephrotoxicity: other aminoglycosides; the antiviral acyclovir; the antifungal amphotericin B; the antibiotics bacitracin, capreomycin, colistin, polymyxin B, and vancomycin; and cisplatin.
Amikacin should not be used with neuromuscular blocking agents, as they can increase muscle weakness and paralysis.
Amikacin can be inactivated by beta-lactams: though still often used with penicillins to create an additive effect against certain bacteria, and carbapenems, which can have a synergistic effect against some Gram-positive bacteria.
Th cephalosporins, a group of bets-lactam can increase the nephrotoxicity of aminoglycoside as well as randomly elevating creatinine levels.
The antibiotics chloramphenicol, clindamycin, and tetracycline can 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, the cholera vaccine, and the live typhoid vaccine by acting as a pharmacological antagonist.
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.
At normal doses, amikacin-sensitive bacteria respond within 24–48 hours.
Amikacin evades attacks by antibiotic-inactivating enzymes that are responsible for antibiotic resistance in bacteria, except for aminoacetyltransferase and nucleotidyltransferase.
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 distributes into the heart, gallbladder, lungs, and bones, 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.[13] 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.
95% of amikacin from an intramuscular or intravenous 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.