Adverse outcome pathway for aminoglycoside ototoxicity in drug-resistant tuberculosis treatment

Hong, Henry; Dooley, Kelly E.; Starbird, Laura E.; Francis, Howard W.; Farley, Jason E.

doi:10.1007/s00204-019-02407-8

Cited by 27 publications

(13 citation statements)

References 145 publications

(213 reference statements)

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“…These alterations can be observed in the presence of pathological conditions, as in the case of AIDS, and when various medications are being taken, as, for instance, anti-retrovirals (6,26). In the auditory system, oxidative stress can make cells more vulnerable, contributing to the death of cells and alterations in the auditory pathway (11,12). The frequent manifestation of auditory abnormalities, from the middle ear to the central auditory nervous system, in individuals with HIV/AIDS has already been known for some time (27).…”

Section: ' Discussionmentioning

confidence: 99%

“…Recent studies in noise-exposed animals suggest that, in addition to the vulnerability of cochlear hair cells because of oxidative stress, there may concomitantly be a process that would damage the synapsis between the hair cells and auditory nerve fibers. This alteration in the synapses could cause an alteration in the processing of acoustic information, even in the presence of hearing thresholds within normality, contributing to the presence of abnormalities, such as speechin-noise difficulties and/or tinnitus (11)(12)(13)36).…”

Section: ' Discussionmentioning

confidence: 99%

“…Studies have shown that oxidative stress contributes to the death of hair cells, which can lead to auditory alterations (11,12). Recently, the oxidative stress resulting from noise exposure (13)(14)(15) and ototoxic medications (4,16) are being related to auditory alterations, even in the presence of hearing thresholds within normality (16)(17)(18).…”

Section: ' Introductionmentioning

confidence: 99%

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Oxidative Stress as a Risk Factor for Hearing Changes in HIV-positive Normal Listeners

Matas¹,

Padilha²,

Angrisani³

et al. 2020

Clinics

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Human immunodeficiency virus-positive (HIV+) individuals can experience a decrease in antioxidants. Such deficiency can make inner ear cells and synapses more vulnerable to oxidative stress, resulting in auditory alterations, even in the presence of normal thresholds. This study aims to compare the audiological findings of HIV+ patients (with and without exposure to anti-retroviral treatment) to those of healthy individuals. METHODS: This was a cross-sectional observational study, comprising 42 normal-hearing adults divided into the Control Group (CG), without HIV; Group I (GI), HIV+, without exposure to the highly active anti-retroviral therapy (HAART); Group II (GII), HIV+, with exposure to HAART. All participants underwent conventional audiometry (0.25-8 kHz), high-frequency audiometry (9-20 kHz), transient evoked otoacoustic emissions (TEOAEs), efferent auditory pathway's inhibitory effect assessment, brainstem auditory evoked potentials (BAEPs), and cognitive potential (P300). RESULTS: In the comparison of the hearing thresholds between the groups, there was a statistically significant difference for most of the frequencies assessed (GII presented hearing thresholds significantly poor when compared with other groups). The presence of TEOAE and the inhibitory effect was also verified in a significantly higher number of individuals in the CG than in the other groups. As for the BAEP, there was a statistically significant difference for the interpeak intervals I-V (GII showed higher values when compared with CG). For P300, there were no statistically significant differences. CONCLUSION: Normal-hearing HIV+ individuals (with and without exposure to HAART) presented with poor performance in the audiological procedures, suggesting the presence of auditory alterations even in the presence of normal-hearing thresholds.

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Section: ' Discussionmentioning

confidence: 99%

Section: ' Discussionmentioning

confidence: 99%

Section: ' Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative Stress as a Risk Factor for Hearing Changes in HIV-positive Normal Listeners

Matas¹,

Padilha²,

Angrisani³

et al. 2020

Clinics

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“…Reactive oxygen species (free radicals) acting as mediators of the aminoglycoside (AG) toxicity appear to trigger cell death. [8] In 2016 the Ugandan national guidelines for the treatment of DR-TB recommended the use of a bedaquiline-based injection-free shorter treatment regimen (the 'modified shorter regimen', mSTR), but based on the severity of the disease and the eligibility criteria for the mSTR, most groups of patients are still being put on the injectionbased regimen. There are limited data in our setting on the ototoxic effect of these injectable drugs among the DR-TB patients.…”

Section: Introductionmentioning

confidence: 99%

Hearing loss among patients on treatment for drug-resistant tuberculosis in Uganda

Lodiong¹,

Amos²,

Lumori³

et al. 2021

SSMJ

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Introduction: Second-line injectable therapy using aminoglycosides (AG) like kanamycin, amikacin or capreomycin is associated with irreversible hearing loss. We aimed to determine the incidence and predictors of hearing loss among patients with drug resistant tuberculosis (DR-TB) who received AG.Method: This was a retrospective cohort study conducted at the tuberculosis treatment unit of Mbarara Regional Referral Hospital (MRRH). All adult patients with a diagnosis of DR-TB between March 2016 and December 2019 were candidates for inclusion in the study. Hearing loss was defined as a hearing threshold of >20 decibels (dB) at any test frequency in at least one ear. The incidence and predictors of hearing loss were analysed using multivariable Cox model. A p-value of ≤0.05 was considered as statistically significant. Data analysis was done using STATA version 13.Results: The estimated rate of developing hearing loss was 107 per 1000 person months. Thirty-seven (52.9%) of 70 DR-TB patients experienced some degree of hearing loss, of which 25 (67.6 %) developed mild, 5 (13.5%) moderate, and 3 (8.1%) severe hearing loss. Male sex (HR 2.05, CI 1.03-4.10, p-value 0.041), increasing age (HR.5.17, CI 1.42-18.87, p-value 0.013) and high BMI (HR 3.31, CI 1.15 - 9.53, p-value 0.026) were significant predictors of new onset of hearing loss.Conclusion: The incidence of hearing loss among DR-TB patients was high, with the majority having a mild hearing loss. Patients who were male, older, overweight and/or obese were more likely to develop AG-induced hearing loss.

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“…Some of these drugs have been identified to have teratogenic effects. For example, aminoglycosides, including streptomycin, kanamycin and amikacin, have been shown to impact fetal birth weight and hearing capacity 6 12 13. As a result, some studies have recommended termination of pregnancy,8 14 and others have suggested reducing the dose of teratogenic drugs or suspending the treatment during pregnancy 15 16.…”

Section: Introductionmentioning

confidence: 99%

Impact of multidrug-resistant tuberculosis and its medications on adverse maternal and perinatal outcomes: protocol for a systematic review and meta-analysis

2019

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IntroductionMultidrug-resistant tuberculosis (MDR-TB) is a common public health problem affecting pregnant women. However, the impact of MDR-TB and its medication on pregnancy and perinatal outcomes has been poorly understood and inconsistently reported. Therefore, using the available literature, we aim to determine whether MDR-TB and its medications during pregnancy impact maternal and perinatal outcomes.Methods and analysisThis systematic review and meta-analysis will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Systematic searches will be conducted in PubMed, Scopus and Web of Science on 10 February 2020 for studies that reported adverse maternal and perinatal outcomes due to MDR-TB and/or its medication. The search will be performed without language and time restrictions. Adverse birth outcomes include miscarriage or abortion, stillbirth, preterm birth, low birth weight, small and large for gestational age, and neonatal death. Two independent reviewers will screen search records, extract data and assess the quality of the studies. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the methodological quality of the included studies. In addition to a narrative synthesis, a random-effects meta-analysis will be conducted when sufficient data are available. I2 statistics will be used to assess the heterogeneity between studies.Ethics and disseminationAs it will be a systematic review and meta-analysis based on previously published evidence, there will be no requirement for ethical approval. Findings will be published in a peer-reviewed journal and will be presented at various conferences.

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Adverse outcome pathway for aminoglycoside ototoxicity in drug-resistant tuberculosis treatment

Cited by 27 publications

References 145 publications

Oxidative Stress as a Risk Factor for Hearing Changes in HIV-positive Normal Listeners

Oxidative Stress as a Risk Factor for Hearing Changes in HIV-positive Normal Listeners

Hearing loss among patients on treatment for drug-resistant tuberculosis in Uganda

Impact of multidrug-resistant tuberculosis and its medications on adverse maternal and perinatal outcomes: protocol for a systematic review and meta-analysis

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