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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]
Tobramycin
 
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

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Antibiotic efficacy varies based on the infection model and treatment regimen for Pseudomonas aeruginosa.
Cigana C, Ranucci S, Rossi A, De Fino I, Melessike M, Bragonzi A
Eur Respir J 2020 Mar;55(3) Epub 2020 Mar 5 doi: 10.1183/13993003.02456-2018. PMID: 31624114Free PMC Article
Loteprednol and tobramycin in combination: a review of their impact on current treatment regimens.
Comstock TL, Holland EJ
Expert Opin Pharmacother 2010 Apr;11(5):843-52. doi: 10.1517/14656561003667532. PMID: 20210687
The treatment of respiratory pseudomonas infection in cystic fibrosis: what drug and which way?
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Curated

DailyMed Drug Label, tobramycin, 2022

DailyMed Drug Label, TOBRAMYCIN, 2013

Recent clinical studies

Etiology

The pharmacokinetics of antibiotics in cystic fibrosis.
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
Dual antibiotics for bronchiectasis.
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
The rationale for aerosolized antibiotics.
Flume P, Klepser ME
Pharmacotherapy 2002 Mar;22(3 Pt 2):71S-79S. doi: 10.1592/phco.22.6.71s.33909. PMID: 11898884
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Ophthalmology 2000 Aug;107(8):1503-6. doi: 10.1016/s0161-6420(00)00227-x. PMID: 10919898
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McCracken GH Jr
Am J Med 1986 Jun 30;80(6B):172-8. doi: 10.1016/0002-9343(86)90497-3. PMID: 3524215

Diagnosis

Dual antibiotics for bronchiectasis.
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
Capnocytophaga keratitis.
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
An overview of amikacin.
Ristuccia AM, Cunha BA
Ther Drug Monit 1985;7(1):12-25. doi: 10.1097/00007691-198503000-00003. PMID: 3887667
Tobramycin-neomycin cross-sensitivity.
Schorr WF, Ridgway HB
Contact Dermatitis 1977 Jun;3(3):133-7. doi: 10.1111/j.1600-0536.1977.tb03627.x. PMID: 891176
Aminoglycoside-resistant enterococci.
Basker MJ, Slocombe B, Sutherland R
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Therapy

The pharmacokinetics of antibiotics in cystic fibrosis.
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
Dual antibiotics for bronchiectasis.
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
Capnocytophaga keratitis.
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
Pharmacokinetic characteristics of piperacillin/tazobactam.
Sörgel F, Kinzig M
Intensive Care Med 1994 Jul;20 Suppl 3:S14-20. doi: 10.1007/BF01745246. PMID: 7962984
Aspects of the pharmacology and toxicology of tobramycin in animals and humans.
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

Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing.
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
An outbreak of Mycobacterium chelonae infection after LASIK.
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
The rationale for aerosolized antibiotics.
Flume P, Klepser ME
Pharmacotherapy 2002 Mar;22(3 Pt 2):71S-79S. doi: 10.1592/phco.22.6.71s.33909. PMID: 11898884
Capnocytophaga keratitis.
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
An overview of amikacin.
Ristuccia AM, Cunha BA
Ther Drug Monit 1985;7(1):12-25. doi: 10.1097/00007691-198503000-00003. PMID: 3887667

Clinical prediction guides

Tobramycin and Colistin display anti-inflammatory properties in CuFi-1 cystic fibrosis cell line.
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
Neonatal Bacterial Conjunctivitis in Korea in the 21st Century.
Pak KY, Kim SI, Lee JS
Cornea 2017 Apr;36(4):415-418. doi: 10.1097/ICO.0000000000001122. PMID: 28002109
The rationale for aerosolized antibiotics.
Flume P, Klepser ME
Pharmacotherapy 2002 Mar;22(3 Pt 2):71S-79S. doi: 10.1592/phco.22.6.71s.33909. PMID: 11898884
An overview of amikacin.
Ristuccia AM, Cunha BA
Ther Drug Monit 1985;7(1):12-25. doi: 10.1097/00007691-198503000-00003. PMID: 3887667
Comparative clinical study of tobramycin and gentamicin.
Klastersky J, Hensgens C, Henri A, Daneau D
Antimicrob Agents Chemother 1974 Feb;5(2):133-8. doi: 10.1128/AAC.5.2.133. PMID: 4599859Free PMC Article

Recent systematic reviews

Comparable Efficacy and Better Safety of Double β-Lactam Combination Therapy versus β‑Lactam plus Aminoglycoside in Gram-Negative Bacteria in Randomized, Controlled Trials.
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
Dual antibiotics for bronchiectasis.
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
Systematic review of the dry powder inhalers colistimethate sodium and tobramycin in cystic fibrosis.
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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