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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

Wüllner D, Gesper M, Haupt A, Liang X, Zhou P, Dietze P, Narberhaus F, Bandow JE
Antimicrob Agents Chemother 2022 Jan 18;66(1):e0087821. Epub 2021 Nov 8 doi: 10.1128/AAC.00878-21. PMID: 34748386Free PMC Article
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Comstock TL, Holland EJ
Expert Opin Pharmacother 2010 Apr;11(5):843-52. doi: 10.1517/14656561003667532. PMID: 20210687

Curated

DailyMed Drug Label, tobramycin, 2022

DailyMed Drug Label, TOBRAMYCIN, 2013

Recent clinical studies

Etiology

Nichols DP, Singh PK, Baines A, Caverly LJ, Chmiel JF, GIbson RL, Lascano J, Morgan SJ, Retsch-Bogart G, Saiman L, Sadeghi H, Billings JL, Heltshe SL, Kirby S, Kong A, Nick JA, Mayer-Hamblett N; TEACH Study Group
Thorax 2022 Jun;77(6):581-588. Epub 2021 Oct 27 doi: 10.1136/thoraxjnl-2021-217782. PMID: 34706982Free PMC Article
Akkerman-Nijland AM, Akkerman OW, Grasmeijer F, Hagedoorn P, Frijlink HW, Rottier BL, Koppelman GH, Touw DJ
Expert Opin Drug Metab Toxicol 2021 Jan;17(1):53-68. Epub 2020 Dec 29 doi: 10.1080/17425255.2021.1836157. PMID: 33213220
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
Alexandrakis G, Palma LA, Miller D, Alfonso EC
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Diagnosis

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
Alexandrakis G, Palma LA, Miller D, Alfonso EC
Ophthalmology 2000 Aug;107(8):1503-6. doi: 10.1016/s0161-6420(00)00227-x. PMID: 10919898
Ristuccia AM, Cunha BA
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Therapy

Akkerman-Nijland AM, Akkerman OW, Grasmeijer F, Hagedoorn P, Frijlink HW, Rottier BL, Koppelman GH, Touw DJ
Expert Opin Drug Metab Toxicol 2021 Jan;17(1):53-68. Epub 2020 Dec 29 doi: 10.1080/17425255.2021.1836157. PMID: 33213220
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
Alexandrakis G, Palma LA, Miller D, Alfonso EC
Ophthalmology 2000 Aug;107(8):1503-6. doi: 10.1016/s0161-6420(00)00227-x. PMID: 10919898
Ristuccia AM, Cunha BA
Ther Drug Monit 1985;7(1):12-25. doi: 10.1097/00007691-198503000-00003. PMID: 3887667
Israel KS, Welles JS, Black HR
J Infect Dis 1976 Aug;134 Suppl:S97-103. doi: 10.1093/infdis/134.supplement_1.s97. PMID: 787452

Prognosis

Wu AY, Gervasio KA, Gergoudis KN, Wei C, Oestreicher JH, Harvey JT
Acta Ophthalmol 2018 Jun;96(4):e503-e509. Epub 2018 Jan 16 doi: 10.1111/aos.13675. PMID: 29338124Free PMC Article
Natale S, Bradley J, Nguyen WH, Tran T, Ny P, La K, Vivian E, Le J
Pharmacotherapy 2017 Mar;37(3):361-378. Epub 2017 Feb 27 doi: 10.1002/phar.1899. PMID: 28079262
Freitas D, Alvarenga L, Sampaio J, Mannis M, Sato E, Sousa L, Vieira L, Yu MC, Martins MC, Hoffling-Lima A, Belfort R Jr
Ophthalmology 2003 Feb;110(2):276-85. doi: 10.1016/S0161-6420(02)01643-3. PMID: 12578767
Alexandrakis G, Palma LA, Miller D, Alfonso EC
Ophthalmology 2000 Aug;107(8):1503-6. doi: 10.1016/s0161-6420(00)00227-x. PMID: 10919898
Ristuccia AM, Cunha BA
Ther Drug Monit 1985;7(1):12-25. doi: 10.1097/00007691-198503000-00003. PMID: 3887667

Clinical prediction guides

Nichols DP, Singh PK, Baines A, Caverly LJ, Chmiel JF, GIbson RL, Lascano J, Morgan SJ, Retsch-Bogart G, Saiman L, Sadeghi H, Billings JL, Heltshe SL, Kirby S, Kong A, Nick JA, Mayer-Hamblett N; TEACH Study Group
Thorax 2022 Jun;77(6):581-588. Epub 2021 Oct 27 doi: 10.1136/thoraxjnl-2021-217782. PMID: 34706982Free PMC Article
Sheikh Z, Bradbury P, Reekie TA, Pozzoli M, Robinson PD, Kassiou M, Young PM, Ong HX, Traini D
Eur J Pharmacol 2021 Jul 5;902:174098. Epub 2021 Apr 20 doi: 10.1016/j.ejphar.2021.174098. PMID: 33848541
Nichols DP, Happoldt CL, Bratcher PE, Caceres SM, Chmiel JF, Malcolm KC, Saavedra MT, Saiman L, Taylor-Cousar JL, Nick JA
J Cyst Fibros 2017 May;16(3):358-366. Epub 2016 Dec 24 doi: 10.1016/j.jcf.2016.12.003. PMID: 28025037Free PMC Article
Pak KY, Kim SI, Lee JS
Cornea 2017 Apr;36(4):415-418. doi: 10.1097/ICO.0000000000001122. PMID: 28002109
Ristuccia AM, Cunha BA
Ther Drug Monit 1985;7(1):12-25. doi: 10.1097/00007691-198503000-00003. PMID: 3887667

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

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