Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on <i>MT‐RNR1</i> Genotype
John McDermott, Joshua Wolf, Keito Hoshitsuki, Rachel Huddart, Kelly E. Caudle, Michelle Whirl‐Carrillo, Peter S. Steyger, Richard J. Smith, Neal Cody, Cristina Rodríguez‐Antona, Teri E. Klein, William G. Newman
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).