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Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT‐RNR1 Genotype
Author(s) -
McDermott John Henry,
Wolf Joshua,
Hoshitsuki Keito,
Huddart Rachel,
Caudle Kelly E.,
WhirlCarrillo Michelle,
Steyger Peter S.,
Smith Richard J. H.,
Cody Neal,
RodriguezAntona Cristina,
Klein Teri E.,
Newman William G.
Publication year - 2022
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.2309
Subject(s) - aminoglycoside , genotype , genetics , hearing loss , ototoxicity , nephrotoxicity , biology , antibiotics , medicine , gene , audiology , kidney , chemotherapy , cisplatin
Aminoglycosides are widely used antibiotics with notable side effects, such as nephrotoxicity, vestibulotoxicity, and sensorineural hearing loss (cochleotoxicity). MT-RNR1 is a gene that encodes the 12s rRNA subunit and is the mitochondrial homologue of the prokaryotic 16s rRNA. Some MT-RNR1 variants (i.e., m.1095T>C; m.1494C>T; m.1555A>G) more closely resemble the bacterial 16s rRNA subunit and result in increased risk of aminoglycoside-induced hearing loss. Use of aminoglycosides should be avoided in individuals with an MT-RNR1 variant associated with an increased risk of aminoglycoside-induced hearing loss unless the high risk of permanent hearing loss is outweighed by the severity of infection and safe or effective alternative therapies are not available. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of aminoglycosides based on MT-RNR1 genotype (updates at https://cpicpgx.org/guidelines/ and www.pharmgkb.org).