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Kanamycin response

MedGen UID:
776650
•Concept ID:
CN184547
•
Sign or Symptom
Drug:
Kanamycin
MedGen UID:
7193
•Concept ID:
C0022487
•
Antibiotic
An aminoglycoside antibiotic with antimicrobial property. Amikacin irreversibly binds to the bacterial 30S ribosomal subunit, specifically in contact with 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 for treatment of E. coli, Proteus species (both indole-positive and indole-negative), E. aerogenes, K. pneumoniae, S. marcescens, and Acinetobacter species. [from NCI]
Kanamycin
 
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

Treatment of Mycobacterium abscessus Pulmonary Disease.
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
Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis.
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
Mycobacterium abscessus: challenges in diagnosis and treatment.
Benwill JL, Wallace RJ Jr
Curr Opin Infect Dis 2014 Dec;27(6):506-10. doi: 10.1097/QCO.0000000000000104. PMID: 25268925

Curated

DailyMed Drug Label, KANAMYCIN, 2012

Recent clinical studies

Etiology

Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis.
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
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
Antibiotics for treating septic abortion.
Udoh A, Effa EE, Oduwole O, Okusanya BO, Okafo O
Cochrane Database Syst Rev 2016 Jul 1;7(7):CD011528. doi: 10.1002/14651858.CD011528.pub2. PMID: 27364644Free 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
Aminoglycoside toxicity in infants and children.
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
Aptasensors for quantitative detection of kanamycin.
Robati RY, Arab A, Ramezani M, Langroodi FA, Abnous K, Taghdisi SM
Biosens Bioelectron 2016 Aug 15;82:162-72. Epub 2016 Apr 5 doi: 10.1016/j.bios.2016.04.011. PMID: 27085947
Endophthalmitis.
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
Ototoxicity in developing mammals.
Henley CM, Rybak LP
Brain Res Brain Res Rev 1995 Jan;20(1):68-90. doi: 10.1016/0165-0173(94)00006-b. PMID: 7711768
An overview of amikacin.
Ristuccia AM, Cunha BA
Ther Drug Monit 1985;7(1):12-25. doi: 10.1097/00007691-198503000-00003. PMID: 3887667

Therapy

Treatment of Mycobacterium abscessus Pulmonary Disease.
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
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
Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events? A systematic review.
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
Endophthalmitis.
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
Ototoxicity in developing mammals.
Henley CM, Rybak LP
Brain Res Brain Res Rev 1995 Jan;20(1):68-90. doi: 10.1016/0165-0173(94)00006-b. PMID: 7711768

Prognosis

Treatment of Mycobacterium abscessus Pulmonary Disease.
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
Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis.
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
Mycobacterium abscessus: challenges in diagnosis and treatment.
Benwill JL, Wallace RJ Jr
Curr Opin Infect Dis 2014 Dec;27(6):506-10. doi: 10.1097/QCO.0000000000000104. PMID: 25268925
The madura foot: looking deep.
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
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

Treatment of Mycobacterium abscessus Pulmonary Disease.
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
The amikacin research program: a stepwise approach to validate dosing regimens in neonates.
Smits A, Kulo A, van den Anker J, Allegaert K
Expert Opin Drug Metab Toxicol 2017 Feb;13(2):157-166. Epub 2016 Sep 21 doi: 10.1080/17425255.2017.1234606. PMID: 27623706
Mycobacterium abscessus: challenges in diagnosis and treatment.
Benwill JL, Wallace RJ Jr
Curr Opin Infect Dis 2014 Dec;27(6):506-10. doi: 10.1097/QCO.0000000000000104. PMID: 25268925
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

Recent systematic reviews

Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis.
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
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
Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events? A systematic review.
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
Antibiotics for treating septic abortion.
Udoh A, Effa EE, Oduwole O, Okusanya BO, Okafo O
Cochrane Database Syst Rev 2016 Jul 1;7(7):CD011528. doi: 10.1002/14651858.CD011528.pub2. PMID: 27364644Free PMC Article

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