Aminoglycoside antibiotics remain widely used for urgent clinical treatment of life-threatening
infections, despite the well-recognized risk of
permanent hearing loss, i.e., cochleotoxicity. Recent studies show that
aminoglycoside-induced cochleotoxicity is exacerbated by bacteriogenic-induced
inflammation. This implies that those with severe
bacterial infections (that induce systemic
inflammation), and are treated with bactericidal
aminoglycosides are at greater risk of
drug-induced
hearing loss than previously recognized. Incorporating this novel comorbid factor into cochleotoxicity risk prediction models will better predict which individuals are more predisposed to
drug-induced
hearing loss. Here, we review the cellular and/or signaling mechanisms by which host-mediated inflammatory responses to
infection could enhance the trafficking of systemically administered
aminoglycosides into the cochlea to enhance the degree of cochleotoxicity over that in healthy preclinical models. Once verified, these mechanisms will be potential targets for novel pharmacotherapeutics that reduce the risk of
drug-induced
hearing loss (and acute kidney damage) without compromising the life-saving bactericidal efficacy of
aminoglycosides.