TABLE 2.
RECOMMENDED THERAPEUTIC USE OF AMINOGLYCOSIDES IN RELATION TO MT-RNR1 PHENOTYPE IN CHILDREN AND ADULTS
| Phenotype | Implications for phenotypic measures | Therapeutic recommendations | Classification of recommendationsa | Considerations |
|---|---|---|---|---|
| MT-RNR1 increased risk of aminoglycoside-induced hearing loss | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic | Avoid aminoglycoside antibiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies. | Strong | If no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring). |
| MT-RNR1 normal risk of aminoglycoside-induced hearing loss | Normal risk of developing hearing loss if administered an aminoglycoside antibiotic. | Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. Evaluate regularly for hearing loss in line with local guidance. | Strong | Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. |
| MT-RNR1 uncertain risk of aminoglycoside-induced hearing loss | Weak or no evidence for an increased risk of MT-RNR1−associated hearing loss if administered an aminoglycoside antibiotic. | Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic drug monitoring. Evaluate regularly for hearing loss in line with local guidance. | Optional | Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses. |
a
Rating scheme described in the Supplemental Material online.