Cisplatin and Aminoglycoside Antibiotics: Hearing Loss and Its Prevention

Abstract:Currently no pharmacogenomics-based criteria exist to guide clinicians in identifying individuals who are at risk of hearing loss from cisplatin-based chemotherapy. This review summarizes findings from pharmacogenomic studies that report genetic polymorphisms associated with cisplatin-induced hearing loss and aims to (1) provide up-to-date information on new developments in the field; (2) provide recommendations for the use of pharmacogenetic testing in the prevention, assessment and management of cisplatin-induced hearing loss in children and adults; and (3) identify knowledge gaps to direct and prioritize future research. These practice recommendations for pharmacogenetic testing in the context of cisplatin-induced hearing loss reflect a review and evaluation of recent literature and are designed to assist clinicians in providing optimal clinical care for patients receiving cisplatin based chemotherapy.

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“…• Aminoglycoside antibiotics share similar toxicity profile with cisplatin, causing nephrototoxicity, neuropathy and ototoxicity 73 .…”

Section: Box 1 Clinical Risk Factors For Cisplatin-induced Ototoxicitymentioning

confidence: 99%

Clinical Practice Recommendations for the Management and Prevention of Cisplatin-Induced Hearing Loss Using Pharmacogenetic Markers

Lee

Pussegoda

Rassekh

et al. 2016

Therapeutic Drug Monitoring

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“…Aminoglycosides have been used to treat TB for more than 40 years 3 . These agents are cost-effective and widely used in lowand middle-income countries 2,3 .…”

Section: Introductionmentioning

confidence: 99%

“…Aminoglycosides have been used to treat TB for more than 40 years 3 . These agents are cost-effective and widely used in lowand middle-income countries 2,3 . Yet, aminoglycoside use for the treatment of MDR-TB is associated with ototoxicity in 5-64% in cases [3][4][5][6][7][8][9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

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The importance of audiometric monitoring in patients with multidrug-resistant tuberculosis

Vasconcelos

Frota

Ruffino-Netto

et al. 2017

Rev. Soc. Bras. Med. Trop.

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Introduction: A total of 771 cases of multidrug-resistant tuberculosis (MDR-TB) were reported in Brazil in 2014. Treatment of MDR-TB with aminoglycosides can produce serious side effects such as permanent and irreversible hearing loss, which occurs in 5-64% of cases, and severely compromise patient quality of life. The goal of this research was to evaluate auditory and vestibular side effects in patients treated for MDR-TB and to identify associations between these complaints and the type of aminoglycoside used. Methods: We performed a retrospective review of 599 medical records from patients with MDR-TB who were treated at the Hélio Fraga/Fiocruz Reference Center between 2006 and 2010. Cases without auditory or vestibular complaints and patients who were not treated with aminoglycoside drugs were excluded from the study. Results: Of 164 eligible cases, 55 (33.5%) reported an auditory or vestibular complaint and medication was subsequently suspended, although hearing damage was not confirmed in all cases. Audiometric testing confirmed hearing loss in 11 (21.7%) of 12 cases submitted for evaluation. Hearing loss related to ototoxicity was confirmed in 15 (62.5%) cases. Tinnitus was significantly associated with the use of amikacin and streptomycin. Conclusions: Evaluations of ototoxicity symptoms were not usually reported in the routine care of patients with MDR-TB. Complaints of tinnitus were associated with amikacin and streptomycin use. These results require confirmation in future studies.

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“…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).…”

Section: Introductionmentioning

confidence: 99%

Assessment of Nutrient Supplement to Reduce Gentamicin-Induced Ototoxicity

Prell

Ojano-Dirain

Rudnick

et al. 2014

JARO

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Gentamicin is an aminoglycoside antibiotic used to treat gram-negative bacterial infections. Treatment with this antibiotic carries the potential for adverse side effects, including ototoxicity and nephrotoxicity. Ototoxic effects are at least in part a consequence of oxidative stress, and various antioxidants have been used to attenuate gentamicin-induced hair cell death and hearing loss. Here, a combination of nutrients previously shown to reduce oxidative stress in the hair cells and attenuate hearing loss after other insults was evaluated for potential protection against gentamicin-induced ototoxicity. Guinea pigs were maintained on a nutritionally complete standard laboratory animal diet or a diet supplemented with β-carotene, vitamins C and E, and magnesium. Three diets with iterative increases in nutrient levels were screened; the final diet selected for study use was one that produced statistically reliable increases in plasma levels of vitamins C and E and magnesium. In two separate studies, significant decreases in gentamicin-induced hearing loss at frequencies including 12 kHz and below were observed, with less benefit at the higher frequencies. Consistent with the functional protection, robust protection of both the inner and outer hair cell populations was observed, with protection largely in the upper half of the cochlea. Protection was independently assessed in two different laboratories, using two different strains of guinea pigs. Additional in vitro tests did not reveal any decrease in antimicrobial activity with nutrient additives. Currently, there are no FDA-approved treatments for the prevention of gentamicin-induced ototoxicity. The current data provide a rationale for continued investigations regarding translation to human patients.

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Cisplatin and Aminoglycoside Antibiotics: Hearing Loss and Its Prevention

Cited by 296 publications

References 158 publications

Clinical Practice Recommendations for the Management and Prevention of Cisplatin-Induced Hearing Loss Using Pharmacogenetic Markers

Clinical Practice Recommendations for the Management and Prevention of Cisplatin-Induced Hearing Loss Using Pharmacogenetic Markers

The importance of audiometric monitoring in patients with multidrug-resistant tuberculosis

Assessment of Nutrient Supplement to Reduce Gentamicin-Induced Ototoxicity

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