Vancomycin-induced ototoxicity in very-low-birthweight infants.


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:
01 08 2020
Historique:
received: 03 12 2019
revised: 15 03 2020
accepted: 17 03 2020
pubmed: 29 5 2020
medline: 25 6 2021
entrez: 29 5 2020
Statut: ppublish

Résumé

Vancomycin is an extensively used anti-infective drug in neonatal ICUs. However, exposure-toxicity relationships have not been clearly defined. To evaluate the risk profile for hearing deficits in vancomycin-exposed very-low-birthweight infants (VLBWI). In a large cohort study of the German Neonatal Network (GNN; n = 16 967 VLBWI) we assessed the association of vancomycin treatment and pathological hearing tests at discharge and at 5 year follow-up. We performed audits on vancomycin exposure, drug levels, dose adjustments and exposure to other ototoxic drugs in a subgroup of 1042 vancomycin-treated VLBWI. In the GNN cohort, 28% (n = 4739) were exposed to IV vancomycin therapy. In multivariable logistic regression analysis, vancomycin exposure proved to be independently associated with pathological hearing test at discharge (OR 1.18, 95% CI 1.03-1.34, P = 0.016). Among vancomycin-treated infants, a cumulative vancomycin dose above the upper quartile (>314 mg/kg bodyweight) was associated with pathological hearing test at discharge (OR 2.1, 95% CI 1.21-3.64, P = 0.009), whereas a vancomycin cumulative dose below the upper quartile was associated with a reduced risk of pathological tone audiometry results at 5 years of age (OR 0.29, 95% CI 0.1-0.8, P = 0.02, n = 147). Vancomycin exposure in VLBWI is associated with an increased, dose-dependent risk of pathological hearing test results at discharge and at 5 years of age. Prospective studies on long-term hearing impairment are needed.

Sections du résumé

BACKGROUND
Vancomycin is an extensively used anti-infective drug in neonatal ICUs. However, exposure-toxicity relationships have not been clearly defined.
OBJECTIVES
To evaluate the risk profile for hearing deficits in vancomycin-exposed very-low-birthweight infants (VLBWI).
METHODS
In a large cohort study of the German Neonatal Network (GNN; n = 16 967 VLBWI) we assessed the association of vancomycin treatment and pathological hearing tests at discharge and at 5 year follow-up. We performed audits on vancomycin exposure, drug levels, dose adjustments and exposure to other ototoxic drugs in a subgroup of 1042 vancomycin-treated VLBWI.
RESULTS
In the GNN cohort, 28% (n = 4739) were exposed to IV vancomycin therapy. In multivariable logistic regression analysis, vancomycin exposure proved to be independently associated with pathological hearing test at discharge (OR 1.18, 95% CI 1.03-1.34, P = 0.016). Among vancomycin-treated infants, a cumulative vancomycin dose above the upper quartile (>314 mg/kg bodyweight) was associated with pathological hearing test at discharge (OR 2.1, 95% CI 1.21-3.64, P = 0.009), whereas a vancomycin cumulative dose below the upper quartile was associated with a reduced risk of pathological tone audiometry results at 5 years of age (OR 0.29, 95% CI 0.1-0.8, P = 0.02, n = 147).
CONCLUSIONS
Vancomycin exposure in VLBWI is associated with an increased, dose-dependent risk of pathological hearing test results at discharge and at 5 years of age. Prospective studies on long-term hearing impairment are needed.

Identifiants

pubmed: 32464660
pii: 5848383
doi: 10.1093/jac/dkaa156
doi:

Substances chimiques

Vancomycin 6Q205EH1VU

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2291-2298

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

Janina Marissen (J)

Department of Paediatrics, University of Luebeck, University Hospital of Schleswig-Holstein, Luebeck, Germany.

Ingmar Fortmann (I)

Department of Paediatrics, University of Luebeck, University Hospital of Schleswig-Holstein, Luebeck, Germany.

Alexander Humberg (A)

Department of Paediatrics, University of Luebeck, University Hospital of Schleswig-Holstein, Luebeck, Germany.

Tanja K Rausch (TK)

Department of Paediatrics, University of Luebeck, University Hospital of Schleswig-Holstein, Luebeck, Germany.
Institute of Medical Biometry and Statistics, University of Luebeck, Luebeck, Germany.

Arne Simon (A)

Department of Paediatric Oncology, Saar University Homburg, Homburg, Germany.

Anja Stein (A)

Department of Paediatrics, University of Essen, Essen, Germany.

Thomas Schaible (T)

Department of Paediatrics, University of Mannheim, Mannheim, Germany.

Joachim Eichhorn (J)

Children's Hospital Leverkusen, Leverkusen, Germany.

Jürgen Wintgens (J)

Children's Hospital Mönchengladbach, Mönchengladbach, Germany.

Claudia Roll (C)

Vestische Children's Hospital Datteln, Datteln, Germany.

Friedhelm Heitmann (F)

Children's Hospital Dortmund, Dortmund, Germany.

Egbert Herting (E)

Department of Paediatrics, University of Luebeck, University Hospital of Schleswig-Holstein, Luebeck, Germany.

Wolfgang Göpel (W)

Department of Paediatrics, University of Luebeck, University Hospital of Schleswig-Holstein, Luebeck, Germany.

Christoph Härtel (C)

Department of Paediatrics, University of Luebeck, University Hospital of Schleswig-Holstein, Luebeck, Germany.
Department of Paediatrics, University of Wuerzburg, Wuerzburg, Germany.

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