Macrolide-associated ototoxicity: a cross-sectional and longitudinal study to assess the association of macrolide use with tinnitus and hearing loss.
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
15 09 2021
15 09 2021
Historique:
received:
02
04
2021
accepted:
03
06
2021
pubmed:
28
7
2021
medline:
29
10
2021
entrez:
27
7
2021
Statut:
ppublish
Résumé
Macrolides are widely prescribed antibiotics for many different indications. However, there are concerns about adverse effects such as ototoxicity. To investigate whether macrolide use is associated with tinnitus and hearing loss in the general population. Cross-sectional (n = 4286) and longitudinal (n = 636) analyses were performed within the population-based Rotterdam Study. We investigated with multivariable logistic regression models the association between macrolides and tinnitus, and with multivariable linear regression models the association between macrolides and two different hearing thresholds (both ears, averaged over 0.25, 0.5, 1, 2, 4 and 8 kHz and 2, 4 and 8 kHz). Both regression models were adjusted for age, sex, systolic blood pressure, alcohol, smoking, BMI, diabetes, education level, estimated glomerular filtration rate and other ototoxic or tinnitus-generating drugs. Cumulative exposure to macrolides was categorized according to the number of dispensed DDDs and duration of action. In the fully adjusted model, ever use of macrolides was associated with a 25% higher likelihood of prevalent tinnitus (OR = 1.25; 95% CI 1.07-1.46). This association was more prominent in participants with a cumulative dose of more than 14 DDDs and among users of intermediate- or long-acting macrolides. Macrolide use in between both assessments was associated with more than a 2-fold increased risk on incident tinnitus. No general association between macrolides and hearing loss was observed. A borderline significant higher hearing threshold in very recent users (≤3 weeks) was found. Macrolide use was significantly associated with both prevalent and incident tinnitus. Macrolide-associated tinnitus was likely cumulative dose-dependent.
Sections du résumé
BACKGROUND
Macrolides are widely prescribed antibiotics for many different indications. However, there are concerns about adverse effects such as ototoxicity.
OBJECTIVES
To investigate whether macrolide use is associated with tinnitus and hearing loss in the general population.
METHODS
Cross-sectional (n = 4286) and longitudinal (n = 636) analyses were performed within the population-based Rotterdam Study. We investigated with multivariable logistic regression models the association between macrolides and tinnitus, and with multivariable linear regression models the association between macrolides and two different hearing thresholds (both ears, averaged over 0.25, 0.5, 1, 2, 4 and 8 kHz and 2, 4 and 8 kHz). Both regression models were adjusted for age, sex, systolic blood pressure, alcohol, smoking, BMI, diabetes, education level, estimated glomerular filtration rate and other ototoxic or tinnitus-generating drugs. Cumulative exposure to macrolides was categorized according to the number of dispensed DDDs and duration of action.
RESULTS
In the fully adjusted model, ever use of macrolides was associated with a 25% higher likelihood of prevalent tinnitus (OR = 1.25; 95% CI 1.07-1.46). This association was more prominent in participants with a cumulative dose of more than 14 DDDs and among users of intermediate- or long-acting macrolides. Macrolide use in between both assessments was associated with more than a 2-fold increased risk on incident tinnitus. No general association between macrolides and hearing loss was observed. A borderline significant higher hearing threshold in very recent users (≤3 weeks) was found.
CONCLUSIONS
Macrolide use was significantly associated with both prevalent and incident tinnitus. Macrolide-associated tinnitus was likely cumulative dose-dependent.
Identifiants
pubmed: 34312676
pii: 6328751
doi: 10.1093/jac/dkab232
pmc: PMC8446930
doi:
Substances chimiques
Anti-Bacterial Agents
0
Macrolides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2708-2716Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
Références
Am J Med. 1992 Jan;92(1):61-8
pubmed: 1731511
Neuroscience. 2019 May 21;407:213-228
pubmed: 30690137
Otol Neurotol. 2003 Jul;24(4):701-2
pubmed: 12851569
Laryngoscope. 1960 Sep;70:1211-28
pubmed: 13715685
Hear Res. 2010 Jun 1;264(1-2):3-9
pubmed: 19853647
Eur Rev Med Pharmacol Sci. 2020 Aug;24(15):7946-7952
pubmed: 32767320
Hear Res. 2016 Jul;337:70-9
pubmed: 27246985
Am J Respir Crit Care Med. 2008 Dec 1;178(11):1139-47
pubmed: 18723437
Arch Intern Med. 1993 Apr 12;153(7):879-82
pubmed: 8466379
Eur J Epidemiol. 2020 May;35(5):483-517
pubmed: 32367290
Am J Otol. 1993 Mar;14(2):186-8
pubmed: 8503495
Lancet Infect Dis. 2014 Aug;14(8):742-750
pubmed: 25022435
Laryngoscope. 2017 Jan;127(1):229-232
pubmed: 27497265
Eur Arch Otorhinolaryngol. 2014 Jul;271(7):1879-84
pubmed: 23990061
Laryngoscope. 2018 Jan;128(1):228-236
pubmed: 28771738
Postgrad Med J. 2005 Jan;81(951):58-9
pubmed: 15640431
J Laryngol Otol. 2001 Aug;115(8):622-8
pubmed: 11535141
Rev Med Virol. 2021 Mar;31(2):e2163
pubmed: 32969125
Cochrane Database Syst Rev. 2019 Jan 18;1:CD011825
pubmed: 30656650
Eur J Epidemiol. 2017 Nov;32(11):993-1005
pubmed: 28825166
Scand Audiol. 1986;15(1):41-2
pubmed: 3704541
Lancet Diabetes Endocrinol. 2016 Jan;4(1):44-51
pubmed: 26575606
J Laryngol Otol. 2003 Dec;117(12):1006-7
pubmed: 14738620
PLoS One. 2017 Aug 15;12(8):e0183192
pubmed: 28813508
Ann Otol Rhinol Laryngol. 2000 Apr;109(4):435-7
pubmed: 10778901
Eur J Public Health. 2013 Feb;23(1):146-52
pubmed: 22197756
J Antimicrob Chemother. 2011 Dec;66 Suppl 6:vi37-45
pubmed: 22096065
Front Neurosci. 2018 Nov 27;12:866
pubmed: 30538616
Int J Pharm Pract. 2021 Feb 10;29(1):21-28
pubmed: 32871046
Clin Drug Investig. 2017 May;37(5):423-437
pubmed: 28197902
Clin Pharmacol Ther. 2017 Apr;101(4):491-500
pubmed: 28002638
Audiol Neurootol. 2016;21 Suppl 1:10-15
pubmed: 27806349
Otol Neurotol. 2018 Sep;39(8):957-963
pubmed: 29965935
Otolaryngol Head Neck Surg. 2021 Apr;164(4):859-868
pubmed: 32988263
Audiol Neurootol. 2018;23(5):290-297
pubmed: 30537711