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.

Figure 1.

Flow diagram of literature search based on preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations. AG, aminoglycoside; GP, glycopeptide.

Figure 2.

Boxplot with overlaid dot plot showing the hearing loss frequencies (%) per disease category. Cross-sectional aetiology studies and studies with a 100% hearing loss were not included in this figure. *Clemens et al. (2016) calculated hearing loss frequencies for gentamicin, tobramycin and vancomycin separately. The central lines represent the median frequency of hearing loss; the boxes represent the frequency of hearing loss within the 25th and 75th quartile; and the whiskers represent the frequency of hearing loss below the 25th quartile and above the 75th quartile.

Figure 3.

Boxplot with overlaid dot plot showing the hearing loss frequencies (%) per aminoglycoside/glycopeptide subtype. Cross-sectional aetiology studies and studies with a 100% hearing loss were not included in this figure. *Clemens et al. (2016) calculated hearing loss frequencies for gentamicin, tobramycin and vancomycin separately. The central lines represent the median frequency of hearing loss; the boxes represent the frequency of hearing loss within the 25th and 75th quartile; and the whiskers represent the frequency of hearing loss below the 25th quartile and above the 75th quartile. Outliers are defined as values 1.5 times the IQR above the upper quartile and below the lower quartile.

Figure 4.

Boxplot with overlaid dot plot showing the hearing loss frequencies (%) per study type. Cross-sectional aetiology studies with a 100% hearing loss were not included in this figure. *Clemens et al. (2016) calculated hearing loss frequencies for gentamicin, tobramycin and vancomycin separately. The central lines represent the median frequency of hearing loss; the boxes represent the frequency of hearing loss within the 25th and 75th quartile; and the whiskers represent the frequency of hearing loss below the 25th quartile and above the 75th quartile.

Figure 5.

Boxplots with overlaid dot plots showing tinnitus and vertigo frequencies (%) per antibiotic subtype. The central lines represent the median frequency of hearing loss; the boxes represent the frequency of hearing loss within the 25th and 75th quartile; and the whiskers represent the frequency of hearing loss below the 25th quartile and above the 75th quartile.