Amikacin

Spectrum: Amikacin is active against Gram-negative and Gram-positive bacteria. Mycobacterium tuberculosis is also susceptible to Amikacin.

Microbiology Applications: Amikacin is commonly used in clinical in vitro microbiological antimicrobial susceptibility tests (panels, discs, and MIC strips) and rapid antimicrobial testing platforms.  Medical microbiologists use this information to recommend antibiotic treatment options.  Samples of microbes grown in presence of a 30 µg Amikacin discs with a zone of inhibition of <14 mm in diameter are considered resistant.  Intermediate resistance zones of inhibition are typically 15 mm-16 mm in diameter.  Representative MIC values include:

• Pseudomonas aeruginosa 0.25 µg/mL -512 µg/mL
• Serratia marcescens ≤0.25 µg/mL － >32 µg/mL
• For a representative list of Amikacin MIC values, click here.

Eukaryotic Cell Culture Applications: Amikacin demonstrates lysosomal phospholipidosis in vitro, with the compound binding to the phospholipid bilayer.

An LC–MS/MS assay was developed to quantify Amikacin in different biological matrices.  This technology can facilitate future studies on improving Amikacin-associated nephrotoxicity.  It would be useful for in vitro studies characterizing Amikacin uptake kinetics in renal cells, and in vivo pharmacokinetic studies (Chan et al, 2020).

Contamination of cell cultures for virus isolation is problematic.  Amikacin (and vancomycin) were chosen to replace the penicillin and gentamicin used conventionally.  This combination was not toxic to cell cultures remained stable in media for over six months.  Virus isolation rate was maintained and contamination was reduced from 10% to 1.5%.  This combination can be used for maintenance and transport media to control the emerging problem of viral culture contamination (Lo et el, 1996).

Form: Powder

Appearance: White or almost white powder

Source: Semi-synthetic

Water Content (Karl Fischer): ≤8.5%

pH: 9.5 - 11.5

Assay: (On Dried Basis): ≥900µg/mg

Residue On Ignition: ≤1.0%

Optical Rotation: +97° to +105°

Identification: Passes test

Solubility: Freely soluble in water (50 mg/ml)

Impurity Profile: Residue on Ignition: ≤1.0%

References:

Chan K,  Wang W , Ledesma KR, Yin T, and Tam VH (2020) A robust LC–MS/MS method for Amikacin: Application to cellular uptake and pharmacokinetic studies. Bioanalysis 12(7):445-454 PMID 32343148

Christophe T et al (2009) High content screening identifies decaprenyl-phosphoribose 2’ epimerase as a target for intracellular antimycobacterial inhibitors. PLoS Pathog. 5(10): e10000645. PMID 19876393

Davis, BD (1987) Mechanism of bactericidal action of aminoglycosides. Microbiol Rev 51 (3 ): 341-50 PMID 3312985

Dudek M, Romanowska J, Witula T, Trylska J (2014) Interactions of Amikacin with the RNA model of the ribosomal A-site: Computational, spectroscopic and calorimetric studies. Biochimie 102:188-202. PMID 24769038

Laurent G, Carlier MB, Rollman B, Van Hoof F, Tulkens P (1982) Mechanism of aminoglycoside-induced lysosomal phospholipidosis: In vitro and in vivo studies with gentamicin and Amikacin. Biochem. Pharmacol 31(23):3861-70. PMID 7159463

Lo JY, Lim WW, Tam BK, Lai MY (1996)  Vancomycin and Amikacin in cell cultures for virus isolation. Pathology. 1996;28(4):366-369  PMID 9007960

Singh R, Ray P, Das A, Sharma MJ (2009) Role of persisters and small-colony variants in antibiotic resistance of planktonic and biofilm-associated Staphylococcus aureus: An in vitro study. Med. Microbiol 58(8):1067-1073  PMID 1952816

Amikacin (TOKU-E)

Parastoo S, Ahya A-A, Soudi MR, Gamazo C and Irache JM (2016)  Amikacin loaded PLGA nanoparticles against Pseudomonas aeruginosa. E. J. Pharm. Sci 93:392-398 PMID 27575877