Hearing loss and vestibular dysfunction among children with cancer after receiving aminoglycosides

Chen, Kenneth; Bach, Alicia; Shoup, Angela G.; Winick, Naomi J.

doi:10.1002/pbc.24631

Cited by 27 publications

(33 citation statements)

References 30 publications

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“…Nephrotoxicity is largely reversible, whilst hearing loss is permanent. Hearing loss occurs in a dose-dependent manner and the antibacterial efficacy, nephrotoxicity, and ototoxicity of these drugs correlate with aminoglycoside blood concentration (Lacy et al, 1998 ; Mingeot-Leclercq and Tulkens, 1999 ; Chen et al, 2013 ). Hence, aminoglycosides are typically administered in inpatient settings and therapeutic drug monitoring of aminoglycoside levels in the blood is routinely performed in most developed countries (Freeman et al, 1997 ; Smyth et al, 2005 ; Agency for Healthcare Research and Quality, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Towards the Prevention of Aminoglycoside-Related Hearing Loss

O’Sullivan

Pérez

Lin

et al. 2017

Front. Cell. Neurosci.

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Aminoglycosides are potent antibiotics deployed worldwide despite their known side-effect of sensorineural hearing loss. The main etiology of this sensory deficit is death of inner ear sensory hair cells selectively triggered by aminoglycosides. For decades, research has sought to unravel the molecular events mediating sensory cell demise, emphasizing the roles of reactive oxygen species and their potentials as therapeutic targets. Studies in recent years have revealed candidate transport pathways including the mechanotransducer channel for drug entry into sensory cells. Once inside sensory cells, intracellular targets of aminoglycosides, such as the mitochondrial ribosomes, are beginning to be elucidated. Based on these results, less ototoxic aminoglycoside analogs are being generated and may serve as alternate antimicrobial agents. In this article, we review the latest findings on mechanisms of aminoglycoside entry into hair cells, their intracellular actions and potential therapeutic targets for preventing aminoglycoside ototoxicity.

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Section: Introductionmentioning

confidence: 99%

Towards the Prevention of Aminoglycoside-Related Hearing Loss

O’Sullivan

Pérez

Lin

et al. 2017

Front. Cell. Neurosci.

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“…Ototoxic hearing loss typically first affects the high frequencies (.8 kHz), may then progress to involve lower frequencies, and is usually bilateral and irreversible. 5,6 Neonates admitted to NICUs have up to a 10fold increase in prevalence of hearing loss. 7,8 Prolonged gentamicin treatment and high trough plasma concentrations (TPCs) have been suggested to increase the risk of ototoxicity.…”

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confidence: 99%

Hearing in Schoolchildren After Neonatal Exposure to a High-Dose Gentamicin Regimen

Hemmingsen

Mikalsen²,

Hansen³

et al. 2020

Pediatrics

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OBJECTIVE:To assess the association between gentamicin exposure in the neonatal period and hearing in school age.METHODS: This study included children exposed to a high-dose (6 mg/kg) gentamicin regimen as neonates (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012), invited for follow-up at school age, and a healthy age-matched control group. We assessed hearing with pure tone audiometry including the extended high-frequency (EHF) range. Outcomes were average hearing thresholds in the midfrequencies (0.5-4 kHz) and the EHFs (9-16 kHz). The measures of gentamicin exposure were cumulative dose and highest trough plasma concentration. We used linear regression models to assess the impact of gentamicin exposure, and other peri-and postnatal morbidities, on hearing thresholds.RESULTS: A total of 219 gentamicin-exposed and 33 healthy-control children were included in the audiological analysis. In the gentamicin cohort, 39 (17%) had a birth weight ,1500 g. Median cumulative doses and trough plasma concentrations were 30 (interquartile range 24-42) mg/kg and 1.0 (interquartile range 0.7-1.2) mg/L, respectively. Median hearing thresholds for the midfrequencies and the EHFs were 2.5 (0 to 6.3) dB hearing level and 21.7 (25.0 to 5.0) dB hearing level, both of which were within the normal range. In an adjusted analysis, increasing hearing thresholds were associated with lower birth weight and postnatal middle-ear disease but not level of gentamicin exposure. After adjusting for birth weight, there was no difference in hearing threshold between the gentamicin-exposed cohort and healthy controls.CONCLUSIONS: Exposure to a high-dose gentamicin regimen in the neonatal period was not associated with an increase in hearing thresholds in schoolchildren being able to complete audiometry.WHAT'S KNOWN ON THIS SUBJECT: Evidence for ototoxic hearing loss after gentamicin exposure is mainly from studies in adults and older children. Neonatal studies report low rates of ototoxicity but have commonly used only moderately sensitive hearing tests.WHAT THIS STUDY ADDS: We performed pure tone audiometry, including the extended high-frequency range, in 219 schoolchildren (median age 9 years) exposed to a high-dose gentamicin regimen in the neonatal period. We found no association between exposure to gentamicin and hearing levels.

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“…In their study, Chen et al conclude that their data highlight the risks of prolonged aminoglycoside administration and warrant further validation in a larger patients group. We suggest completing this phrase by adding: “… especially if treated with multiple daily doses.”…”

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confidence: 92%

“…To the Editor: We read with interest the report from Chen et al describing the development of hear impairment in 23 children receiving amikacin for treatment of febrile neutropenia at a dose of 7.5 mg/kg q8h, “with doses adjusted to achieve appropriate peak and trough concentrations.”…”

mentioning

confidence: 99%