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Practice Guideline
. 2022 Feb;111(2):366-372.
doi: 10.1002/cpt.2309. Epub 2021 Jun 20.

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype

John Henry McDermott  1   2 , Joshua Wolf  3 , Keito Hoshitsuki  4 , Rachel Huddart  5 , Kelly E Caudle  6 , Michelle Whirl-Carrillo  5 , Peter S Steyger  7 , Richard J H Smith  8 , Neal Cody  9   10 , Cristina Rodriguez-Antona  11 , Teri E Klein  5   12 , William G Newman  1   2
Affiliations
Practice Guideline

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype

John Henry McDermott et al. Clin Pharmacol Ther. 2022 Feb.

Abstract

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).

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Conflict of interest statement

CONFLICTS OF INTEREST

N.C. is an assistant laboratory director in the pharmacogenomics division at Mount Sinai Genomics Inc, DBA Sema4. All other authors declared no competing interests for this work.

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