Dataset Information

Aminoglycoside- and glycopeptide-induced ototoxicity in children: a systematic review.

ABSTRACT:

Background

Ototoxicity has been reported after administration of aminoglycosides and glycopeptides.

Objectives

To identify available evidence for the occurrence and determinants of aminoglycoside- and glycopeptide-related ototoxicity in children.

Materials and methods

Systematic electronic literature searches that combined ototoxicity (hearing loss, tinnitus and/or vertigo) with intravenous aminoglycoside and/or glycopeptide administration in children were performed in PubMed, EMBASE and Cochrane Library databases. Studies with sample sizes of ≥50 children were included. The QUIPS tool and Cochrane criteria were used to assess the quality and risk of bias of included studies.

Results

Twenty-nine aminoglycoside-ototoxicity studies met the selection criteria (including 7 randomized controlled trials). Overall study quality was medium/low. The frequency of hearing loss within these studies ranged from 0%-57%, whereas the frequency of tinnitus and vertigo ranged between 0%-53% and 0%-79%, respectively. Two studies met the criteria on glycopeptide-induced ototoxicity and reported hearing loss frequencies of 54% and 55%. Hearing loss frequencies were higher in gentamicin-treated children compared to those treated with other aminoglycosides. In available studies aminoglycosides had most often been administered concomitantly with platinum agents, diuretics and other co-medication.

Conclusions

In children the reported occurrence of aminoglycoside/glycopeptide ototoxicity highly varies and seems to depend on the diagnosis, aminoglycoside subtype and use of co-administered medication. More research is needed to investigate the prevalence and determinants of aminoglycoside/glycopeptide ototoxicity. Our results indicate that age-dependent audiological examination may be considered for children frequently treated with aminoglycosides/glycopeptides especially if combined with other ototoxic medication.

SUBMITTER: Diepstraten FA

PROVIDER: S-EPMC8669239 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Aminoglycoside- and glycopeptide-induced ototoxicity in children: a systematic review.

Diepstraten F A FA Hoetink A E AE van Grotel M M Huitema A D R ADR Stokroos R J RJ van den Heuvel-Eibrink M M MM Meijer A J M AJM

JAC-antimicrobial resistance 20211214 4

<h4>Background</h4>Ototoxicity has been reported after administration of aminoglycosides and glycopeptides.<h4>Objectives</h4>To identify available evidence for the occurrence and determinants of aminoglycoside- and glycopeptide-related ototoxicity in children.<h4>Materials and methods</h4>Systematic electronic literature searches that combined ototoxicity (hearing loss, tinnitus and/or vertigo) with intravenous aminoglycoside and/or glycopeptide administration in children were performed in PubM ...[more]

PMID: 34917943

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Project description:BackgroundIrreversible hearing loss is a well-known adverse effect of aminoglycosides, however, inability to accurately predict ototoxicity is a major limitation in clinical care. We addressed this limitation by developing a prediction model for aminoglycoside ototoxicity applicable to the general population.MethodsWe employed a prospective non-drug-resistant tuberculosis (TB), non-HIV/AIDS cohort of 153 adults on Streptomycin based anti-TB therapy. High frequency pure-tone audiometry was done at regular intervals throughout the study. Clinical and audiological predictors of ototoxicity were collated and ototoxic threshold shift from the baseline audiogram computed. The prediction model was developed with logistic regression method by examining multiple predictors of ototoxicity. Series of models were fitted sequentially; the best model was identified using Akaike Information Criterion and likelihood ratio test. Key variables in the final model were used to develop a logit model for ototoxicity prediction.ResultsOtotoxicity occurred in 35% of participants. Age, gender, weight, cumulative Streptomycin dosage, social class, baseline pure tone average (PTA) and prior hearing symptoms were explored as predictors. Multiple logistic regression showed that models with age, cumulative dosage and baseline PTA were best for predicting ototoxicity. Regression parameters for ototoxicity prediction showed that yearly age increment raised ototoxicity risk by 5% (AOR = 1.05; CI, 1.01-1.09), and a gram increase in cumulative dosage increased ototoxicity risk by 7% (AOR = 1.05; CI, 1.05-1.12) while a unit change in baseline log (PTA) was associated 254% higher risk of ototoxicity (AOR = 3.54, CI: 1.25, 10.01). Training and validation models had area under the receiver operating characteristic curve as 0.84 (CI, 0.76-0.92) and 0.79 (CI, 0.62-0.96) respectively, showing the model has discriminatory ability.ConclusionThis model can predict aminoglycoside ototoxicity in the general population.

Project description:ImportanceAminoglycosides are commonly prescribed antibiotics used for the treatment of neonatal sepsis. The MT-RNR1 m.1555A>G variant predisposes to profound aminoglycoside-induced ototoxicity (AIO). Current genotyping approaches take several days, which is unfeasible in acute settings.ObjectiveTo develop a rapid point-of-care test (POCT) for the m.1555A>G variant before implementation of this technology in the acute neonatal setting to guide antibiotic prescribing and avoid AIO.Design, setting, and participantsThis pragmatic prospective implementation trial recruited neonates admitted to 2 large neonatal intensive care units between January 6, 2020, and November 30, 2020, in the UK.InterventionsNeonates were tested for the m.1555A>G variant via the rapid POCT on admission to the neonatal intensive care unit.Main outcomes and measuresThe primary outcome assessed the proportion of neonates successfully tested for the variant of all infants prescribed antibiotics. Secondary outcomes measured whether implementation was negatively associated with routine clinical practice and the performance of the system. The study was statistically powered to detect a significant difference between time to antibiotic administration before and after implementation of the MT-RNR1 POCT.ResultsA total of 751 neonates were recruited and had a median (range) age of 2.5 (0-198) days. The MT-RNR1 POCT was able to genotype the m.1555A>G variant in 26 minutes. Preclinical validation demonstrated a 100% sensitivity (95% CI, 93.9%-100.0%) and specificity (95% CI, 98.5%-100.0%). Three participants with the m.1555A>G variant were identified, all of whom avoided aminoglycoside antibiotics. Overall, 424 infants (80.6%) receiving antibiotics were successfully tested for the variant, and the mean time to antibiotics was equivalent to previous practice.Conclusions and relevanceThe MT-RNR1 POCT was integrated without disrupting normal clinical practice, and genotype was used to guide antibiotic prescription and avoid AIO. This approach identified the m.1555A>G variant in a practice-changing time frame, and wide adoption could significantly reduce the burden of AIO.

Dataset Information

Aminoglycoside- and glycopeptide-induced ototoxicity in children: a systematic review.

Background

Objectives

Materials and methods

Results

Conclusions

Publications

Aminoglycoside- and glycopeptide-induced ototoxicity in children: a systematic review.

Similar Datasets

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