The Role of A1555G in Aminoglycoside-Induced Ototoxicity: A Systematic Review

Ototoxic hearing loss refers to a decline in hearing sensitivity resulting from drug-induced damage to the inner ear . Ototoxicity often presents as a symmetric, high-frequency hearing loss, although audiogram shape and severity is highly variable across individuals. Over 100 classes of drugs have been described as ototoxic, the most common of which include loop diuretics, platinum-based chemotherapy drugs, and aminoglycosides (Mudd, 2016). Aminoglycosides are a class of antibiotics that are used in the treatment of gram-negative bacterial infections. The oto- and nephrotoxic properties of aminoglycosides have been well-documented. Consequently, these medications are typically reserved for life-threatening infections in the United States and other developed countries. Examples of clinical use include treating chronic lung infections in cases of cystic fibrosis and combating sepsis in preterm infants. Aminoglycosides are more routinely prescribed in developing countries due to their low-cost and high efficacy. In recent decades, advancements in pharmacogenetics have sparked interest in the effect of genetics on susceptibility to aminoglycoside ototoxicity . The AI555G mitochondrial gene mutation is one genetic variant that has received significant investigative attention. Previous research has suggested that individuals who carry the A1555G mutation are more susceptible to aminoglycoside-induced hearing loss relative to the general population (Jing et al., 2014). Ototoxic hearing loss is often irreversible and, like all forms of hearing impairment, can have detrimental effects on language, cognition, social development, and quality of life. Careful audiologic monitoring of patients at risk for ototoxic hearing loss is vital to reducing these negative outcomes. If associated with increased risk of ototoxic hearing loss, identification of the A1555G mutation calls for more frequent monitoring and, when possible, reduction in exposure to aminoglycosides. Understanding the risk factors of ototoxic hearing loss in combination with specific genetic makeups will aid prevention and timely intervention in this clinical population. The aim of this project was to conduct a systematic review on the role of the A1555G mitochondrial mutation in aminoglycoside ototoxicity