Amikacin (formerly Apothecon's Amikin) is an aminoglycoside antibiotic used to treat different types of bacterial infections. Amikacin works by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth.
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
Medical uses
Amikacin is most often used for treating severe, hospital-acquired infections with multidrug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter, and Enterobacter. Serratia marcescens and Providencia stuartii are also included in the spectrum. 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.
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.
Bacterial susceptibility data
Amikacin is usually used as a last-resort medication against multidrug-resistant bacteria. The following represents susceptibility data on a few medically significant microorganisms.
- Pseudomonas aeruginosa - 0.5 μg/mL - 32 μg/mL
- Pseudomonas aeruginosa (aminoglycoside-resistant) - 32 μg/mL - 64 μg/mL
- Serratia marcescens - ≤0.25 μg/mL - 8 μg/mL
- Serratia marcescens (multidrug-resistant) - 32 μg/mL
Adverse effects
Side-effects of amikacin are similar to those of other aminoglycosides. Kidney damage and hearing loss are the most important effects. Because of this potential, blood levels of the drug and markers of kidney function (creatinine) may be monitored. Moreover, doses are adjusted specifically based upon serum Creatinine clearance in clinical settings.
Administration
Amikacin may be administered once or twice a day but must be given by the intravenous or intramuscular route or 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.
Resistance
Amikacin has high resistance against bacterial inactivation. It resists attacks by most bacterial inactivating enzymes. This is accomplished by the L-hydroxyaminobuteroyl amide (L-HABA) moiety attached to N-1 (compare to kanamycin), which inhibits acetylation, phosphorylation, and adenylation in the distant amino sugar ring (C-2,C-3,C-4). To prevent the development of bacterial resistance to this antibiotic, its use is tightly regulated.
Synthesis
Amikacin, is a semisynthetic antibiotic that is synthesized from kanamycin. The primary amino group in this molecule is previously protected by acylating it with N-(carboxybenzyl)oxysuccinimide in DMF, after which the resulting product is treated with an ester synthesized from N-hydroxysuccinimide and (S)-N-Carbobenzyloxy-4-amino-2-hydroxybutyric acid, and as a result one of the unprotected remaining amino groups in the (desoxy)streptamine region of the molecule is selectively acylated. Further removal of the two Cbz protective groups via hydrogen reduction using a palladium on carbon catalyst, forms the desired amikacin.
References
- Edson RS, Terrell CL. The aminoglycosides. Mayo Clin Proc. 1999 May;74(5):519-28. Review. PMID 10319086
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