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Comparing amikacin and kanamycin-induced hearing loss in multidrug-resistant tuberculosis treatment under programmatic conditions in a Namibian retrospective cohort

BACKGROUND: Amikacin and kanamycin are mainly used for treating multidrug-resistant tuberculosis (MDR-TB), especially in developing countries where the burden of MDR-TB is highest. Their protracted use in MDR-TB treatment is known to cause dose-dependent irreversible hearing loss, requiring hearing...

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Autores principales: Sagwa, Evans L., Ruswa, Nunurai, Mavhunga, Farai, Rennie, Timothy, Leufkens, Hubert G. M., Mantel-Teeuwisse, Aukje K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675035/
https://www.ncbi.nlm.nih.gov/pubmed/26654443
http://dx.doi.org/10.1186/s40360-015-0036-7
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author Sagwa, Evans L.
Ruswa, Nunurai
Mavhunga, Farai
Rennie, Timothy
Leufkens, Hubert G. M.
Mantel-Teeuwisse, Aukje K.
author_facet Sagwa, Evans L.
Ruswa, Nunurai
Mavhunga, Farai
Rennie, Timothy
Leufkens, Hubert G. M.
Mantel-Teeuwisse, Aukje K.
author_sort Sagwa, Evans L.
collection PubMed
description BACKGROUND: Amikacin and kanamycin are mainly used for treating multidrug-resistant tuberculosis (MDR-TB), especially in developing countries where the burden of MDR-TB is highest. Their protracted use in MDR-TB treatment is known to cause dose-dependent irreversible hearing loss, requiring hearing aids, cochlear implants or rehabilitation. Therapeutic drug monitoring and regular audiological assessments may help to prevent or detect the onset of hearing loss, but these services are not always available or affordable in many developing countries. We aimed to compare the cumulative incidence of hearing loss among patients treated for MDR-TB with amikacin or kanamycin-based regimens, and to identify the most-at-risk patients, based on the real-life clinical practice experiences in Namibia. METHODS: We conducted a retrospective cohort study of patients treated with amikacin or kanamycin-based regimens in four public sector MDR-TB treatment sites in Namibia between June 2004 and March 2014. Patients were audiologically assessed as part of clinical care. The study outcome was the occurrence of any hearing loss. Data were manually extracted from patients’ treatment records. We compared proportions using the Chi-square test; applied stratified analysis and logistic regression to study the risk of hearing loss and to identify the most-at-risk patients through effect-modification analysis. A P-value < 0.05 was statistically significant. RESULTS: All 353 patients had normal baseline hearing, 46 % were HIV co-infected. Cumulative incidence of any hearing loss was 58 %, which was mostly bilateral (83 %), and mild (32 %), moderate (23 %), moderate-severe (16 %), severe (10 %), or profound (15 %). Patients using amikacin had a greater risk of developing the more severe forms of hearing loss than those using kanamycin (adjusted odds ratio (OR) = 4.0, 95 % CI: 1.5–10.8). Patients co-infected with HIV (OR = 3.4, 95 % CI: 1.1–10.6), males (OR = 4.5, 95 %1.5–13.4) and those with lower baseline body weight (40–59 kg, OR = 2.8, 95 % CI: 1.1–6.8), were most-at-risk of developing hearing loss. CONCLUSION: Amikacin use in the long-term MDR-TB treatment led to a higher risk of occurrence of the more severe forms of hearing loss compared to kanamycin use. Males, patients with low baseline body weight and those co-infected with HIV were most-at-risk. MDR-TB treatment programmes should consider replacing amikacin with kanamycin and strengthen the routine renal, serum therapeutic drug levels and audiometric monitoring in the most-at-risk patients treated with aminoglycosides. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40360-015-0036-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-46750352015-12-11 Comparing amikacin and kanamycin-induced hearing loss in multidrug-resistant tuberculosis treatment under programmatic conditions in a Namibian retrospective cohort Sagwa, Evans L. Ruswa, Nunurai Mavhunga, Farai Rennie, Timothy Leufkens, Hubert G. M. Mantel-Teeuwisse, Aukje K. BMC Pharmacol Toxicol Research Article BACKGROUND: Amikacin and kanamycin are mainly used for treating multidrug-resistant tuberculosis (MDR-TB), especially in developing countries where the burden of MDR-TB is highest. Their protracted use in MDR-TB treatment is known to cause dose-dependent irreversible hearing loss, requiring hearing aids, cochlear implants or rehabilitation. Therapeutic drug monitoring and regular audiological assessments may help to prevent or detect the onset of hearing loss, but these services are not always available or affordable in many developing countries. We aimed to compare the cumulative incidence of hearing loss among patients treated for MDR-TB with amikacin or kanamycin-based regimens, and to identify the most-at-risk patients, based on the real-life clinical practice experiences in Namibia. METHODS: We conducted a retrospective cohort study of patients treated with amikacin or kanamycin-based regimens in four public sector MDR-TB treatment sites in Namibia between June 2004 and March 2014. Patients were audiologically assessed as part of clinical care. The study outcome was the occurrence of any hearing loss. Data were manually extracted from patients’ treatment records. We compared proportions using the Chi-square test; applied stratified analysis and logistic regression to study the risk of hearing loss and to identify the most-at-risk patients through effect-modification analysis. A P-value < 0.05 was statistically significant. RESULTS: All 353 patients had normal baseline hearing, 46 % were HIV co-infected. Cumulative incidence of any hearing loss was 58 %, which was mostly bilateral (83 %), and mild (32 %), moderate (23 %), moderate-severe (16 %), severe (10 %), or profound (15 %). Patients using amikacin had a greater risk of developing the more severe forms of hearing loss than those using kanamycin (adjusted odds ratio (OR) = 4.0, 95 % CI: 1.5–10.8). Patients co-infected with HIV (OR = 3.4, 95 % CI: 1.1–10.6), males (OR = 4.5, 95 %1.5–13.4) and those with lower baseline body weight (40–59 kg, OR = 2.8, 95 % CI: 1.1–6.8), were most-at-risk of developing hearing loss. CONCLUSION: Amikacin use in the long-term MDR-TB treatment led to a higher risk of occurrence of the more severe forms of hearing loss compared to kanamycin use. Males, patients with low baseline body weight and those co-infected with HIV were most-at-risk. MDR-TB treatment programmes should consider replacing amikacin with kanamycin and strengthen the routine renal, serum therapeutic drug levels and audiometric monitoring in the most-at-risk patients treated with aminoglycosides. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40360-015-0036-7) contains supplementary material, which is available to authorized users. BioMed Central 2015-12-10 /pmc/articles/PMC4675035/ /pubmed/26654443 http://dx.doi.org/10.1186/s40360-015-0036-7 Text en © Sagwa et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Sagwa, Evans L.
Ruswa, Nunurai
Mavhunga, Farai
Rennie, Timothy
Leufkens, Hubert G. M.
Mantel-Teeuwisse, Aukje K.
Comparing amikacin and kanamycin-induced hearing loss in multidrug-resistant tuberculosis treatment under programmatic conditions in a Namibian retrospective cohort
title Comparing amikacin and kanamycin-induced hearing loss in multidrug-resistant tuberculosis treatment under programmatic conditions in a Namibian retrospective cohort
title_full Comparing amikacin and kanamycin-induced hearing loss in multidrug-resistant tuberculosis treatment under programmatic conditions in a Namibian retrospective cohort
title_fullStr Comparing amikacin and kanamycin-induced hearing loss in multidrug-resistant tuberculosis treatment under programmatic conditions in a Namibian retrospective cohort
title_full_unstemmed Comparing amikacin and kanamycin-induced hearing loss in multidrug-resistant tuberculosis treatment under programmatic conditions in a Namibian retrospective cohort
title_short Comparing amikacin and kanamycin-induced hearing loss in multidrug-resistant tuberculosis treatment under programmatic conditions in a Namibian retrospective cohort
title_sort comparing amikacin and kanamycin-induced hearing loss in multidrug-resistant tuberculosis treatment under programmatic conditions in a namibian retrospective cohort
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675035/
https://www.ncbi.nlm.nih.gov/pubmed/26654443
http://dx.doi.org/10.1186/s40360-015-0036-7
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