U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Amikacin response

MedGen UID:
776649
Concept ID:
CN184546
Sign or Symptom
Drug:
Amikacin
MedGen UID:
1863
Concept ID:
C0002499
Antibiotic
A broad-spectrum semi-synthetic aminoglycoside antibiotic, derived from kanamycin with antimicrobial property. Amikacin irreversibly binds to the bacterial 30S ribosomal subunit, specifically locking 16S rRNA and S12 protein within the 30S subunit. This leads to interference with translational initiation complex and misreading of mRNA, thereby hampering protein synthesis and resulting in bactericidal effect. This agent is usually used in short-term treatment of serious infections due to susceptible strains of Gram-negative bacteria. [from NCI]

Definition

Aminoglycosides are widely used antibiotics which inhibit protein synthesis in bacteria by binding to bacterial 16S ribosomal subunits. Aminoglycosides are associated with a number of adverse events, including nephrotoxicity and ototoxicity. The risk of aminoglycoside-induced ototoxicity is increased in patients who carry certain variants in the MT-RNR1 gene. MT-RNR1 is found in the mitochondrial genome and encodes the 12S ribosomal subunit. Some MT-RNR1 variants cause the 12S subunit to more closely resemble the bacterial 16S subunit, which can lead to aminoglycoside molecules binding to the ribosome. This ultimately results in hearing loss due to cell death in the cochlea. The Clinical Pharmacogenetics Implementation Consortium (CPIC) have published recommendations on aminoglycoside use in patients carrying MT-RNR1 variants in the journal Clinical Pharmacology and Therapeutics. These recommendations are also available on the CPIC and PharmGKB websites. [from PharmGKB]

Additional description

From GeneReviews
Mitochondrial nonsyndromic hearing loss and deafness is characterized by sensorineural hearing loss (SNHL) of variable onset and severity. Pathogenic variants in MT-RNR1 can be associated with predisposition to aminoglycoside ototoxicity and/or late-onset SNHL. Hearing loss associated with aminoglycoside ototoxicity is bilateral and severe to profound, occurring within a few days to weeks after administration of any amount (even a single dose) of an aminoglycoside antibiotic such as gentamycin, tobramycin, amikacin, kanamycin, or streptomycin. Pathogenic variants in MT-TS1 are usually associated with childhood onset of SNHL that is generally nonsyndromic – although the MT-TS1 substitution m.7445A>G has been found in some families who also have palmoplantar keratoderma (scaling, hyperkeratosis, and honeycomb appearance of the skin of the palms, soles, and heels).

Term Hierarchy

Professional guidelines

PubMed

Griffith DE, Daley CL
Chest 2022 Jan;161(1):64-75. Epub 2021 Jul 24 doi: 10.1016/j.chest.2021.07.035. PMID: 34314673
Lan Z, Ahmad N, Baghaei P, Barkane L, Benedetti A, Brode SK, Brust JCM, Campbell JR, Chang VWL, Falzon D, Guglielmetti L, Isaakidis P, Kempker RR, Kipiani M, Kuksa L, Lange C, Laniado-Laborín R, Nahid P, Rodrigues D, Singla R, Udwadia ZF, Menzies D; Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment 2017
Lancet Respir Med 2020 Apr;8(4):383-394. Epub 2020 Mar 17 doi: 10.1016/S2213-2600(20)30047-3. PMID: 32192585Free PMC Article
Perry CM, Markham A
Drugs 1999 May;57(5):805-43. doi: 10.2165/00003495-199957050-00017. PMID: 10353303

Curated

DailyMed Drug Label, AMIKACIN, 2013

Recent clinical studies

Etiology

Dumoulin M, Pottel H, Mekahli D, Laenen A, Smits A, Allegaert K
Pediatr Nephrol 2024 Aug;39(8):2525-2532. Epub 2024 Mar 25 doi: 10.1007/s00467-024-06335-3. PMID: 38526762Free PMC Article
Margalit I, Lebeaux D, Tishler O, Goldberg E, Bishara J, Yahav D, Coussement J
Clin Microbiol Infect 2021 Apr;27(4):550-558. Epub 2021 Jan 5 doi: 10.1016/j.cmi.2020.12.019. PMID: 33418019
Shirley M
Drugs 2019 Apr;79(5):555-562. doi: 10.1007/s40265-019-01095-z. PMID: 30877642Free PMC Article
Selimoglu E
Curr Pharm Des 2007;13(1):119-26. doi: 10.2174/138161207779313731. PMID: 17266591
Perry CM, Markham A
Drugs 1999 May;57(5):805-43. doi: 10.2165/00003495-199957050-00017. PMID: 10353303

Diagnosis

Dumoulin M, Pottel H, Mekahli D, Laenen A, Smits A, Allegaert K
Pediatr Nephrol 2024 Aug;39(8):2525-2532. Epub 2024 Mar 25 doi: 10.1007/s00467-024-06335-3. PMID: 38526762Free PMC Article
Kim SR, Yu JY, Kim SY, Kim DH, Jhun BW
Microbiol Spectr 2023 Aug 17;11(4):e0205123. Epub 2023 Jul 10 doi: 10.1128/spectrum.02051-23. PMID: 37428038Free PMC Article
Margalit I, Lebeaux D, Tishler O, Goldberg E, Bishara J, Yahav D, Coussement J
Clin Microbiol Infect 2021 Apr;27(4):550-558. Epub 2021 Jan 5 doi: 10.1016/j.cmi.2020.12.019. PMID: 33418019
Patel R, Sise A, Al-Mohtaseb Z, Garcia N, Aziz H, Amescua G, Pantanelli SM
Cornea 2015 Dec;34(12):1617-9. doi: 10.1097/ICO.0000000000000634. PMID: 26418432
Elder MJ, Morlet N; EPSWA. Endophthalmitis Population Study of Western Australia
Clin Exp Ophthalmol 2002 Dec;30(6):394-8. doi: 10.1046/j.1442-9071.2002.00567.x. PMID: 12427228

Therapy

Sawka A, Burke A
Clin Chest Med 2023 Dec;44(4):815-828. Epub 2023 Aug 14 doi: 10.1016/j.ccm.2023.06.012. PMID: 37890918
Kim SR, Yu JY, Kim SY, Kim DH, Jhun BW
Microbiol Spectr 2023 Aug 17;11(4):e0205123. Epub 2023 Jul 10 doi: 10.1128/spectrum.02051-23. PMID: 37428038Free PMC Article
Griffith DE, Daley CL
Chest 2022 Jan;161(1):64-75. Epub 2021 Jul 24 doi: 10.1016/j.chest.2021.07.035. PMID: 34314673
Selimoglu E
Curr Pharm Des 2007;13(1):119-26. doi: 10.2174/138161207779313731. PMID: 17266591
Elder MJ, Morlet N; EPSWA. Endophthalmitis Population Study of Western Australia
Clin Exp Ophthalmol 2002 Dec;30(6):394-8. doi: 10.1046/j.1442-9071.2002.00567.x. PMID: 12427228

Prognosis

Griffith DE, Daley CL
Chest 2022 Jan;161(1):64-75. Epub 2021 Jul 24 doi: 10.1016/j.chest.2021.07.035. PMID: 34314673
Patel R, Sise A, Al-Mohtaseb Z, Garcia N, Aziz H, Amescua G, Pantanelli SM
Cornea 2015 Dec;34(12):1617-9. doi: 10.1097/ICO.0000000000000634. PMID: 26418432
Venkatswami S, Sankarasubramanian A, Subramanyam S
Int J Low Extrem Wounds 2012 Mar;11(1):31-42. Epub 2012 Feb 14 doi: 10.1177/1534734612438549. PMID: 22334597
Selimoglu E
Curr Pharm Des 2007;13(1):119-26. doi: 10.2174/138161207779313731. PMID: 17266591
Ghosh G, Chakraborty S, Ray J, Mukherjee SK
J Indian Med Assoc 1995 Oct;93(10):382, 384. PMID: 9053412

Clinical prediction guides

Dumoulin M, Pottel H, Mekahli D, Laenen A, Smits A, Allegaert K
Pediatr Nephrol 2024 Aug;39(8):2525-2532. Epub 2024 Mar 25 doi: 10.1007/s00467-024-06335-3. PMID: 38526762Free PMC Article
Griffith DE, Daley CL
Chest 2022 Jan;161(1):64-75. Epub 2021 Jul 24 doi: 10.1016/j.chest.2021.07.035. PMID: 34314673
Bilton D, Pressler T, Fajac I, Clancy JP, Sands D, Minic P, Cipolli M, Galeva I, Solé A, Quittner AL, Liu K, McGinnis JP 2nd, Eagle G, Gupta R, Konstan MW; CLEAR-108 Study Group
J Cyst Fibros 2020 Mar;19(2):284-291. Epub 2019 Aug 23 doi: 10.1016/j.jcf.2019.08.001. PMID: 31451351Free PMC Article
Alibi S, Ferjani A, Boukadida J, Cano ME, Fernández-Martínez M, Martínez-Martínez L, Navas J
Sci Rep 2017 Aug 28;7(1):9704. doi: 10.1038/s41598-017-10081-y. PMID: 28848236Free PMC Article
Nagai J, Takano M
Drug Metab Pharmacokinet 2004 Jun;19(3):159-70. doi: 10.2133/dmpk.19.159. PMID: 15499183

Recent systematic reviews

Qin JP, Huang HB, Zhou H, Zhu Y, Xu Y, Du B
Sci Rep 2021 Mar 26;11(1):6969. doi: 10.1038/s41598-021-86342-8. PMID: 33772055Free PMC Article
Margalit I, Lebeaux D, Tishler O, Goldberg E, Bishara J, Yahav D, Coussement J
Clin Microbiol Infect 2021 Apr;27(4):550-558. Epub 2021 Jan 5 doi: 10.1016/j.cmi.2020.12.019. PMID: 33418019
Lan Z, Ahmad N, Baghaei P, Barkane L, Benedetti A, Brode SK, Brust JCM, Campbell JR, Chang VWL, Falzon D, Guglielmetti L, Isaakidis P, Kempker RR, Kipiani M, Kuksa L, Lange C, Laniado-Laborín R, Nahid P, Rodrigues D, Singla R, Udwadia ZF, Menzies D; Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment 2017
Lancet Respir Med 2020 Apr;8(4):383-394. Epub 2020 Mar 17 doi: 10.1016/S2213-2600(20)30047-3. PMID: 32192585Free PMC Article
Shafiq N, Malhotra S, Gautam V, Kaur H, Kumar P, Dutta S, Ray P, Kshirsagar NA
Indian J Med Res 2017 Mar;145(3):299-316. doi: 10.4103/ijmr.IJMR_723_15. PMID: 28749392Free PMC Article
Jenkins A, Thomson AH, Brown NM, Semple Y, Sluman C, MacGowan A, Lovering AM, Wiffen PJ; (BSAC Working Party on Therapeutic Drug Monitoring)
J Antimicrob Chemother 2016 Oct;71(10):2754-9. Epub 2016 Jul 11 doi: 10.1093/jac/dkw250. PMID: 27494904

Supplemental Content

Table of contents

    Genetic Testing Registry

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...