New developments in aminoglycoside therapy and ototoxicity

Abstract

After almost seven decades in clinical use, aminoglycoside antibiotics still remain indispensible drugs for acute infections and specific indications such as tuberculosis or the containment of pseudomonas bacteria in patients with cystic fibrosis. The review will describe the pathology and pathophysiology of aminoglycoside-induced auditory and vestibular toxicity in humans and experimental animals and explore contemporary views of the mechanisms of cell death. It will also outline the current state of protective therapy and recent advances in the development of aminoglycoside derivatives with low toxicity profiles for antimicrobial treatment and for stop-codon suppression in the attenuation of genetic disorders.

Bax, Bcl2, and p53 Differentially Regulate Neomycin- and Gentamicin-Induced Hair Cell Death in the Zebrafish Lateral Line

“…Aminoglycoside use in developed countries is widespread in cystic fibrosis patients and premature infants; worldwide, these drugs are more widely used due to their low cost and high efficacy against a variety of severe or recalcitrant bacterial infections, including drug-resistant tuberculosis (Rizzi and Hirose 2007;Durante-Mangoni et al 2009). Aminoglycoside ototoxicity, resulting in hearing loss and balance disorders, is a serious clinical issue for up to 20 % of patients who received these lifesustaining antibiotics (reviewed in Rizzi and Hirose 2007;Xie et al 2011). Despite early recognition of the ototoxic side effects of aminoglycoside treatment, the cellular pathways underlying aminoglycoside-induced sensorineural hearing loss and balance disorders are not fully understood (Cheng et al 2005;Schacht and Hawkins 2006;Warchol 2010).…”

Assessment of Nutrient Supplement to Reduce Gentamicin-Induced Ototoxicity

“…Drugs such as neomycin, tobramycin, kanamycin, streptomycin, amikacin, and gentamicin can affect hearing, balance, or both (Clark 1977;Xie et al 2011;Ahmed et al 2012). Despite potential ototoxicity and nephrotoxicity, aminoglycosides remain a drug of choice for use against gramnegative bacteria (see Xie et al 2011;Mulheran et al 2001;Hanberger et al 2013;Edson and Terrell 1999).…”

“…Development of otoprotective agents is well-grounded in work on the mechanisms of gentamicin-induced pathology. The key role of free radicals in aminoglycoside-induced hearing loss has been well documented (Xie et al 2011;Schacht et al 2012). The OHC population is a primary target, as OHC loss has been observed in human patient temporal bones, particularly in the basal turn (Kusunoki et al 2004;Backus et al 1987;Keene et al 1982;Johnsson et al 1981).…”

“…A variety of investigations into antioxidant defense against gentamicin insult and other aminoglycosides have been encouraging (for reviews, see Xie et al 2011;Rybak and Kelly 2003;Rybak and Whitworth 2005;Abi-Hachem et al 2010;Poirrier et al 2010;Campbell and Le Prell 2012). There are now a variety of drugs and other substances that have been shown to effectively attenuate cell death and hearing loss after gentamicin insult, although complete protection has been elusive (for summary, see Table 1).…”

The Effects of Hyperbaric Oxygen Therapy Against Streptomycin Ototoxicity

“…After almost eight decades in clinical use, although the ototoxic effects of aminoglycosides in animals and humans are well documented and also high occurrence risk of another serious complication such as nephrotoxicity, this class of drugs seems still likely to remain an important component of medical treatment options due to: 1) the effectiveness at the treatment of gramnegative aerobic bacterial infections, 2) being an alternative medication among the rare options of treatment in tuberculosis, 3) beneficial effects in Meniere's disease and 4) relatively low cost [1][2][3][4][5][6]. Aminoglycoside antibiotics may injure the outer hair cells at the basal turn of the cochlea and cause sensorineural hearing loss.…”