Gentamicin response

Gentamicin is an aminoglycoside antibiotic that is commonly used to treat sepsis in premature infants. Brand names include Garamycin, Cidomycin, and Setpopal. Gentamicin is administered by injection to treat serious infections caused by Gram-negative bacteria (e.g., Pseudomonas aeruginosa, Proteus species, Escherichia coli, Klebsiella-Enterobacter-Serratia species, and Citrobacter species), and is used as an adjuvant treatment for infections caused by Gram-positive bacteria (e.g., Staphylococcus species). Gentamicin may also be used topically to treat ophthalmic and dermatological infections. In most patients, prolonged exposure to high gentamicin levels will cause ototoxicity (damage to the inner ear). However, in individuals who carry specific variants in the mitochondrial gene, MT-RNR1, a single dose of gentamicin can result in hearing loss. This toxicity occurs in genetically susceptible individuals even though the serum drug level is within therapeutic range. In most studies, 100% of individuals with the MT-RNR1 variant known as m.1555A>G (NC_012920.1:m.1555A>G) developed hearing loss after receiving aminoglycoside therapy. The onset of hearing loss varies, but once it occurs, the hearing loss is usually moderate to profound, bilateral, and irreversible. Currently, the FDA-approved drug label for gentamicin does not include a statement about MT-RNR1. However, a 2014 American College of Medical Genetics and Genomics (ACMG) guideline includes the following recommendation: “Single-gene testing may be warranted in cases in which the medical or family history, or presentation of the hearing loss, suggests a specific etiology. For example, testing for mitochondrial DNA mutations associated with aminoglycoside ototoxicity may be considered for individuals with a history of use of aminoglycoside antibiotics”.

Medical Genetics Summaries