Pharmacist-administered audiology screening for pediatric cystic fibrosis patients exposed to high-dose aminoglycosides: A pilot study.

This pilot study successfully implemented a standardized protocol for tablet-based ototoxicity screening in pediatric cystic fibrosis (CF) patients exposed to aminoglycosides. Further studies are needed to assess the impact of implementation in a larger number of patients, as well as to determine barriers that may exist at centers with variation in available resources. This method of ototoxicity screening represents an accessible alternative to traditional audiology testing, and given the continued improvements in expected life span for people with CF, it is imperative that patients have regular access to this type of screening to allow for early identification of medication-related toxicities.

A longitudinal community-based ototoxicity monitoring programme and treatment effects for drug-resistant tuberculosis treatment, Western Cape.

BACKGROUND:  South Africa has a high burden of drug-resistant tuberculosis (DRTB) and until recently, ototoxic aminoglycosides were predominant in treatment regimens. Community-based ototoxicity monitoring programmes (OMPs) have been implemented for early detection of hearing loss and increased patient access. OBJECTIVES:  A longitudinal study was conducted to describe the service delivery characteristics of a community-based OMP for DRTB patients facilitated by CHWs as well as observed ototoxic hearing loss in this population. METHOD:  A descriptive retrospective record review of longitudinal ototoxicity monitoring of 194 DRTB patients undergoing treatment at community-based clinics in the city of Cape Town between 2013 and 2017. RESULTS:  Follow-up rates between consecutive monitoring assessments reached as high as 80.6% for patients assessed by CHWs. Few patients (14.2% - 32.6%) were assessed with the regularity (≥ 6 assessments) and frequency required for effective ototoxicity monitoring, with assessments conducted, on average, every 53.4-64.3 days. Following DRTB treatment, 51.5% of patients presented with a significant ototoxic shift meeting one or more of the American Speech-Language-Hearing Association (ASHA) criteria. Deterioration in hearing thresholds was bilateral and most pronounced at high frequencies (4 kHz - 8 kHz). The presence of pre-existing hearing loss, human immunodeficiency virus co-infection and a history of noise exposure were significant predictors of ototoxicity in patients. CONCLUSION:  DRTB treatment with kanamycin resulted in significant deterioration of hearing longitudinally, predominantly at high frequencies. With ongoing training and supportive supervision, CHWs can facilitate community-based ototoxicity monitoring of DRTB patients. Current protocols and guidelines may require reassessment for appropriate community-based ototoxicity monitoring.

Community-Based Ototoxicity Monitoring for Drug-Resistant Tuberculosis in South Africa: An Evaluation Study.

In response to the drug-resistant tuberculosis (DRTB) ototoxicity burden in South Africa, ototoxicity monitoring has been decentralised, with community health workers (CHWs) acting as facilitators. This study describes a community-based ototoxicity monitoring programme (OMP) for patients with DRTB. Findings are compared to the recommended guidelines for ototoxicity monitoring, the OMP protocol and published studies. This was a retrospective study of longitudinal ototoxicity monitoring of 831 patients with DRTB, using data collected at community-based clinics in the City of Cape Town between 2013 and 2017. Approximately half (46.8%) of the patients had an initial assessment conducted in accordance with the OMP protocol recommendations, and follow-up rates (79.5%) were higher than those of a similar DRTB programme. However, patients in this study were not monitored within the timeframes or with the regularity recommended by the guidelines or the OMP protocol. Extended high-frequency pure-tone audiometry (27.5%) was underutilised by testers and data recording was inconsistent (e.g., 37.7% of patient gender was not recorded by testers). Community-based OMP using CHWs to facilitate monitoring showed improvement over previous hospital-based reports, with more accessible services and higher follow-up rates. However, to improve OMP outcomes, OMP managers should reassess current protocols and data recording practices.

SARS-CoV-2 (COVID-19) and audio-vestibular disorders.

To describe the audio-vestibular disorders related to the newly SARS-CoV-2 infection, including the possible ototoxicity side-effects related to the use of drugs included in the SARS-CoV-2 treatment protocols. A systematic review was performed according to the PRISMA protocol. The Medline and Embase databases were searched from March 1, 2020 to April 9, 2021. Initially the search yielded 400 manuscripts, which were reduced to 15, upon the application of inclusion criteria. Sensorineural hearing loss (SNHL) is the most frequent audio-vestibular symptom described, occurring alone or in association with tinnitus and vertigo. The etiopathogenesis of the inner ear disorders related to COVID-19 infection is still poorly understood. The number of reports of COVID-19 infections associated to audio-vestibular disorders is increasing; even if the quality of the studies available is often insufficient, audio-vestibular disorders should be considered as possible manifestations to be included among the symptoms of this infection.

A Narrative Review of Pharmacologic Treatments for COVID-19: Safety Considerations and Ototoxicity.

OBJECTIVE/HYPOTHESIS: The purpose of this review is to summarize evidence-based data regarding the ototoxic effects of potential COVID-19 therapeutics to treat patients suffering from SARS-CoV-2. METHODS: Medications under investigation as novel therapeutics to treat COVID-19 were identified using the search term coronavirus therapeutics, COVID therapeutics, and SARS-CoV-2 therapeutics on ClinicalTrials.gov and the PubMed Database. A literature review was performed using the PubMed Database for each proposed COVID-19 therapeutic to identify relevant articles. Search criteria included Medical Subject Headings (MeSH) and key word search terms for ototoxicity, vestibulotoxicity, hearing disorders, and vertigo. RESULTS: Six proposed COVID-19 therapeutics were identified as possessing ototoxic side effects including chloroquine and hydroxychloroquine, azithromycin, lopinavir-ritonavir, interferon, ribavirin, and ivermectin. CONCLUSIONS: Available evidence suggests that ototoxic effects may be improved or mitigated by stopping the offending agent. Recognition of hearing loss, tinnitus, or imbalance/vertigo is therefore crucial to facilitate early intervention and prevent long-term damage. Hospitals should consider the inclusion of audiologic monitoring protocols for patients receiving COVID-19 therapeutics with known ototoxicity, especially in high-risk patient groups such as the elderly and hearing impaired. Laryngoscope, 131:1626-1632, 2021.

Ototoxicity prevention during the SARS-CoV-2 (COVID-19) emergency.

Aim of this paper is to remind the risk of ototoxicity when using chloroquine and hydroxychloroquine, in particular as prophylactic agents against SARS-CoV-2, during the pandemic. Healthy subjects taking chloroquine and hydroxychloroquine as prophylactic agents against SARS-CoV-2, during the pandemic, should be screened periodically, at least by Otoacoustic Emissions (OAEs) in order to detect early manifestations of possible cochlear ototoxic damages.

Don't forget ototoxicity during the SARS-CoV-2 (Covid-19) pandemic!

Aim of this communication is to remind clinical professionals to be aware of ototoxic side effects of several specific drugs proposed for the treatment of the new virus SARS-CoV-2 (Covid-19). In particular, chloroquine and hydroxychloroquine, azithromycin, as well as antiviral drugs such as remdesivir, favipiravir and lopinavir can all present potential ototoxic side effects. The data in the literature do not offer specific information on their potential synergetic effects nor on their interactions.

Chloroquine kills hair cells in zebrafish lateral line and murine cochlear cultures: Implications for ototoxicity.

Hearing and balance deficits have been reported during and following treatment with the antimalarial drug chloroquine. However, experimental work examining the direct actions of chloroquine on mechanoreceptive hair cells in common experimental models is lacking. This study examines the effects of chloroquine on hair cells using two common experimental models: the zebrafish lateral line and neonatal mouse cochlear cultures. Zebrafish larvae were exposed to varying concentrations of chloroquine phosphate or hydroxychloroquine for 1 h or 24 h, and hair cells assessed by antibody staining. A significant, dose-dependent reduction in the number of surviving hair cells was seen across conditions for both exposure periods. Hydroxychloroquine showed similar toxicity. In mouse cochlear cultures, chloroquine damage was specific to outer hair cells in tissue from the cochlear basal turn, consistent with susceptibility to other ototoxic agents. These findings suggest a need for future studies employing hearing and balance monitoring during exposure to chloroquine and related compounds, particularly with interest in these compounds as therapeutics against viral infections including coronavirus.

Chloroquine and hydroxychloroquine ototoxicity; potential implications for SARS-CoV-2 treatment. A brief review of the literature.

INTRODUCTION: Current clinical evidences do not support any specific treatment against SARS-CoV-2. Chloroquine (CQ) and hydroxychloroquine (HCQ) are typically used in the treatment of rheumatoid arthritis, systemic lupus erythematosus and malaria; they have been considered for off-label and compassionate use in several countries against moderate to severe cases of COVID-19 and there's actually a massive demand of these two drugs. The aim of this paper is to briefly review the published literature, summarizing evidences about audiological implications after CQ and HCQ treatment. METHODS: We conducted a review of the literature on Medline and Pubmed platforms from 27th May 2020 to 30 May 2020. We combined MeSH terms of "chloroquine", "hydroxychloroquine", "ototoxicity", "hearing loss", "tinnitus", "deafness" and "hearing". Publications with relevant data were included. Selected data (authors, country and year; sample size; study design; audiological side effects) were extracted and summarized in a table. RESULTS: Of 45 initial studies, 14 met inclusion criteria. The authors found xix cases of HCQ ototoxicity; Tinnitus was reported in 2 cases, and it was found to be reversible or irreversible. Sensorineural hearing loss after HCQ use was reported in 7 patients; it was found to be irreversible or partially reversible after discontinuation of HCQ in 6 cases. Eight papers reporting CQ ototoxicity were; tinnitus was not reported by any authors. Sensorineural hearing loss after taking CQ was reported in 6 patients; it was found to be irreversible after discontinuation of CQ in 5 patients. One patient showed abnormal gait after a single intramuscular injection of CQ. Thirteen patients' Auditory Brainstem Response (ABR) were found to be abnormal, but they resolved after CQ discontinuation. CONCLUSIONS: CQ and HCQ related ototoxicity is widely reported in the literature although the pathophysiological mechanism is not well known. Current data are not sufficient enough to support the use of CQ and HCQ as therapy for COVID-19, but considering the growing demand for these two drugs and the number of people around the world who have taken and will take CQ and HCQ, it must necessarily consider the clinical and social impact of long term audiological side effects.

Clinical Implications of Chloroquine and Hydroxychloroquine Ototoxicity for COVID-19 Treatment: A Mini-Review.

At this time of the COVID-19 pandemic, potentially effective treatments are currently under urgent investigation. Benefits of chloroquine and hydroxychloroquine for the treatment of COVID-19 infection have been proposed and clinical trials are underway. Chloroquine and hydroxychloroquine, typically used for the treatment of malaria and autoimmune diseases, have been considered for off-label use in several countries. In the literature, there are reports of ototoxic effects of the drugs causing damage to the inner ear structures, which then result in hearing loss, tinnitus, and/or imbalance. This mini-review represents a summary of the findings from a systematic search regarding ototoxicity of chloroquine and hydroxychloroquine in the published literature. The characteristics of sensorineural hearing loss and/or tinnitus after chloroquine or hydroxychloroquine treatment can be temporary but reports of persistent auditory and vestibular dysfunction exist. These are not frequent, but the impact can be substantial. Additionally, abnormal cochleovestibular development in the newborn was also reported after chloroquine treatment in pregnant women. The suggested dose of chloroquine for COVID-19 infection is considerably higher than the usual dosage for malaria treatment; therefore, it is plausible that the ototoxic effects will be greater. There are potential implications from this review for survivors of COVID-19 treated with chloroquine or hydroxychloroquine. Patient reports of hearing loss, tinnitus, or imbalance should be noted. Those with troublesome hearing loss, tinnitus and/or imbalance are encouraged to be referred for hearing evaluation and interventions once they are stable. Clinical trials of chloroquine or hydroxychloroquine should also consider including audiological monitoring in the protocol.