U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Tobramycin response

MedGen UID:
776648
Concept ID:
CN184545
Sign or Symptom
Drug:
Tobramycin
MedGen UID:
21572
Concept ID:
C0040341
Antibiotic
An aminoglycoside antibiotic derived from Streptomyces tenebrarius with bacteriostatic activity. Following active transport into the cell, tobramycin binds irreversibly to a specific aminoglycoside receptor on the bacterial 30S ribosomal subunit and interferes with the initiation complex between messenger RNA and the 30S subunit, thereby inhibiting initiation of protein synthesis, consequently leading to bacterial cell death. In addition, tobramycin induces misreading of the mRNA template causing incorrect amino acids to be incorporated into the growing polypeptide chain, consequently interfering with protein elongation. [from NCI]
 
Genes (locations): MT-RNR1; MT-TS1; RNR1 (13p12); TRMU (22q13.31)

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

Comstock TL, Holland EJ
Expert Opin Pharmacother 2010 Apr;11(5):843-52. doi: 10.1517/14656561003667532. PMID: 20210687
Rimola A, Navasa M, Arroyo V
Diagn Microbiol Infect Dis 1995 May-Jun;22(1-2):141-5. doi: 10.1016/0732-8893(95)00089-s. PMID: 7587029
Bodey GP, Ketchel S, Rodriguez V
J Infect Dis 1978 May;137 Suppl:S139-S143. doi: 10.1093/infdis/137.supplement.s139. PMID: 649998

Curated

DailyMed Drug Label, tobramycin, 2022

DailyMed Drug Label, TOBRAMYCIN, 2013

Recent clinical studies

Etiology

Ahuja V, Krishnappa M
Int J Risk Saf Med 2022;33(1):49-64. doi: 10.3233/JRS-210021. PMID: 34924402
Schwartz FA, Christophersen L, Laulund AS, Lundquist R, Lerche C, Rude Nielsen P, Bundgaard H, Høiby N, Moser C
APMIS 2021 Nov;129(11):653-662. Epub 2021 Oct 18 doi: 10.1111/apm.13182. PMID: 34580927
Sindeldecker D, Moore K, Li A, Wozniak DJ, Anderson M, Dusane DH, Stoodley P
Antimicrob Agents Chemother 2020 Aug 20;64(9) doi: 10.1128/AAC.00623-20. PMID: 32540981Free PMC Article
Pak KY, Kim SI, Lee JS
Cornea 2017 Apr;36(4):415-418. doi: 10.1097/ICO.0000000000001122. PMID: 28002109
Comstock TL, Holland EJ
Expert Opin Pharmacother 2010 Apr;11(5):843-52. doi: 10.1517/14656561003667532. PMID: 20210687

Diagnosis

Pak KY, Kim SI, Lee JS
Cornea 2017 Apr;36(4):415-418. doi: 10.1097/ICO.0000000000001122. PMID: 28002109
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
James A, Larson T
Ren Fail 2015 Jul;37(6):1061-6. Epub 2015 Jun 9 doi: 10.3109/0886022X.2015.1052949. PMID: 26056733
Hannah BA, Kimmel PL, Dosa S, Turner ML
South Med J 1990 Jun;83(6):720-2. doi: 10.1097/00007611-199006000-00035. PMID: 2356503
Bannatyne RM, Cheung R
Antimicrob Agents Chemother 1981 Oct;20(4):493-5. doi: 10.1128/AAC.20.4.493. PMID: 6979305Free PMC Article

Therapy

de Velde F, Mouton JW, de Winter BCM, van Gelder T, Koch BCP
Pharmacol Res 2018 Aug;134:280-288. Epub 2018 Jul 6 doi: 10.1016/j.phrs.2018.07.005. PMID: 30033398
Pak KY, Kim SI, Lee JS
Cornea 2017 Apr;36(4):415-418. doi: 10.1097/ICO.0000000000001122. PMID: 28002109
Comstock TL, Holland EJ
Expert Opin Pharmacother 2010 Apr;11(5):843-52. doi: 10.1517/14656561003667532. PMID: 20210687
Sörgel F, Kinzig M
Intensive Care Med 1994 Jul;20 Suppl 3:S14-20. doi: 10.1007/BF01745246. PMID: 7962984
Nicolau D, Quintiliani R, Nightingale CH
Conn Med 1992 Oct;56(10):561-3. PMID: 1458882

Prognosis

Tang W, Liu D, Traynelis SF, Yuan H
Neuropharmacology 2020 Oct 15;177:108247. Epub 2020 Jul 24 doi: 10.1016/j.neuropharm.2020.108247. PMID: 32712275Free PMC Article
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
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
James A, Larson T
Ren Fail 2015 Jul;37(6):1061-6. Epub 2015 Jun 9 doi: 10.3109/0886022X.2015.1052949. PMID: 26056733
Comstock TL, Holland EJ
Expert Opin Pharmacother 2010 Apr;11(5):843-52. doi: 10.1517/14656561003667532. PMID: 20210687

Clinical prediction guides

Almatrood W, Nakouti I, Hobbs G
Arch Microbiol 2022 May 4;204(6):297. doi: 10.1007/s00203-022-02877-y. PMID: 35508818Free PMC Article
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
Pak KY, Kim SI, Lee JS
Cornea 2017 Apr;36(4):415-418. doi: 10.1097/ICO.0000000000001122. PMID: 28002109
Elborn JS, Flume PA, Cohen F, Loutit J, VanDevanter DR
J Cyst Fibros 2016 Sep;15(5):634-40. Epub 2016 Feb 28 doi: 10.1016/j.jcf.2016.01.005. PMID: 26935334
Comstock TL, Holland EJ
Expert Opin Pharmacother 2010 Apr;11(5):843-52. doi: 10.1517/14656561003667532. PMID: 20210687

Recent systematic reviews

Jiao Y, Moya B, Chen MJ, Zavascki AP, Tsai H, Tao X, Sutaria DS, Louie A, Boyce JD, Deveson Lucas D, Kim TH, Tsuji BT, Bonomo RA, Drusano GL, Bulitta JB
Antimicrob Agents Chemother 2019 Jul;63(7) Epub 2019 Jun 24 doi: 10.1128/AAC.00425-19. PMID: 30988147Free PMC Article
Felix LM, Grundy S, Milan SJ, Armstrong R, Harrison H, Lynes D, Spencer S
Cochrane Database Syst Rev 2018 Jun 11;6(6):CD012514. doi: 10.1002/14651858.CD012514.pub2. PMID: 29889304Free PMC Article
Uttley L, Harnan S, Cantrell A, Taylor C, Walshaw M, Brownlee K, Tappenden P
Eur Respir Rev 2013 Dec;22(130):476-86. doi: 10.1183/09059180.00001513. PMID: 24293463Free PMC Article

Supplemental Content

Table of contents

    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...