Aminoglycosides are widely used antibiotics that have reported significant side effects such as nephrotoxicity, vestibulotoxicity and hearing loss. Some variants in the MT-RNR1 gene are associated with an increased risk of hearing loss induced by this family of drugs, so their use is generally discouraged in carriers.
Aminoglycoside antibiotics (Adverse effects)
Aminoglycosides are a family of antibiotics widely used for the treatment of bacterial infections. Their safety profile is well studied, they have demonstrated broad efficacy and can be used in combination with other antibiotics such as beta-lactams. Streptomycin was the first aminoglycoside antibiotic isolated in 1943 and since then the class has grown significantly to include others such as neomycin, gentamicin, tobramycin, amikacin, netilmicin, paromomycin, kanamycin, framycetin, dibekacin, sisomycin, isepamycin or plazomycin.
These antibiotics are especially effective against gram-negative bacteria, although they are also active for gram-positive bacteria. Gram-negative bacteria that are treated with aminoglycosides include: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Providencia spp, Proteus spp, Morganella spp, Serratia spp, Yersinia pestis, and Francisella tularensis. Gram-positive bacteria that are treated with aminoglycosides include: Staphylococcus aureus, Pseudomonas aeruginosa , and Acinetobacter baumannii.
At high doses or in prolonged treatment, aminoglycosides can have significant side effects, so their use is usually restricted to the treatment of severe infections such as pneumonia or septicemia. They can be administered orally, topically, ophthalmically and parenterally, the latter being the most effective.
The main side effects of these antibiotics are nephrotoxicity, ototoxicity, neurotoxicity and neuromuscular blockade, which are more frequent in the elderly or in prolonged treatment. Ototoxicity is usually reversible, although there are cases of permanent deafness associated with the presence of mutations in the MT-RNR1 gene of the mitochondrial DNA, present in 1-5% of the population. The identification of these variants is of great utility in preventing aminoglycoside-induced ototoxicity. In these individuals, the use of this family of aminoglycosides should be restricted to situations in which the benefit outweighs the risk.
Genes analyzed
12S RNA (MTRNR1)
Bibliography
Dean L, Kane M.Gentamicin Therapy and MT-RNR1 Genotype. 2015 Apr 29 [updated 2022 Sep 22]. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012–.
Gao Z, Chen Y, Guan MX. Mitochondrial DNA mutations associated with aminoglycoside induced ototoxicity. J Otol. 2017 Mar;12(1):1-8.
McDermott JH, Mahaveer A, James RA, et al. Rapid Point-of-Care Genotyping to Avoid Aminoglycoside-Induced Ototoxicity in Neonatal Intensive Care. JAMA Pediatr. 2022 May 1;176(5):486-492.
McDermott JH et al. Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype. CPIC guideline. May 2021.
Prezant TR, Agapian JV, Bohlman MC, Bu X, et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet. 1993 Jul;4(3):289-94.
Rivetti S, Romano A, Mastrangelo S, et al. Aminoglycosides-Related Ototoxicity: Mechanisms, Risk Factors, and Prevention in Pediatric Patients. Pharmaceuticals (Basel). 2023 Sep 25;16(10):1353.
