Aminoglycosides-Related Ototoxicity: Mechanisms, Risk Factors, and Prevention in Pediatric Patients

Rivetti, Serena; Romano, Alberto; Mastrangelo, Stefano; Attinà, Giorgio; Maurizi, Palma; Ruggiero, Antonio

doi:10.3390/ph16101353

Cited by 7 publications

(3 citation statements)

References 166 publications

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“…Streptomycin and gentamicin are mainly vestibulotoxic, while amikacin, neomycin and kanamycin are preferentially cochleotoxic. Tobramicin is equally vestibulotoxic and cochleotoxic [ 26 , 27 ].…”

Section: Antibiotics For Which the Role Of Genetics In Conditioning D...mentioning

confidence: 99%

“…When cell respiration is perturbed, the overproduction of superoxide occurs, together with cell apoptosis and the development of ear damage. Moreover, some AGs act on the composition of the otolithic membrane, thus changing its characteristics and causing vestibular damage [ 27 ]. Though the development of deafness represents a significant limitation regardless of the patient’s age, this clinical problem is considered a tragic event when it occurs in younger children as it can have a negative impact on language development, literacy, self-esteem and social skills [ 28 ].…”

Section: Antibiotics For Which the Role Of Genetics In Conditioning D...mentioning

confidence: 99%

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Genetic Variations and Antibiotic-Related Adverse Events

Principi,

Petropulacos,

Esposito

2024

Pharmaceuticals

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Antibiotic-related adverse events are common in both adults and children, and knowledge of the factors that favor the development of antibiotic-related adverse events is essential to limit their occurrence and severity. Genetics can condition the development of antibiotic-related adverse events, and the screening of patients with supposed or demonstrated specific genetic mutations may reduce drug-related adverse events. This narrative review discusses which genetic variations may influence the risk of antibiotic-related adverse events and which conclusions can be applied to clinical practice. An analysis of the literature showed that defined associations between genetic variations and specific adverse events are very few and that, at the moment, none of them have led to the implementation of a systematic screening process for patients that must be treated with a given antibiotic in order to select those at risk of specific adverse events. On the other hand, in most of the cases, more than one variation is implicated in the determination of adverse events, and this can be a limitation in planning a systematic screening. Moreover, presently, the methods used to establish whether a patient carries a “dangerous” genetic mutation require too much time and waiting for the result of the test can be deleterious for those patients urgently requiring therapy. Further studies are needed to definitively confirm which genetic variations are responsible for an increased risk of a well-defined adverse event.

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Section: Antibiotics For Which the Role Of Genetics In Conditioning D...mentioning

confidence: 99%

Section: Antibiotics For Which the Role Of Genetics In Conditioning D...mentioning

confidence: 99%

Genetic Variations and Antibiotic-Related Adverse Events

Principi,

Petropulacos,

Esposito

2024

Pharmaceuticals

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“…However, fluoroquinolones and aminoglycosides are antibiotics associated with toxicity in humans, − thus hindering their development as antivirals. To understand the requirements for −1PRF inhibitors devoid of toxicity, new compounds targeting this mechanism must be identified.…”

Section: Introductionmentioning

confidence: 99%

Novel Inhibitors of SARS-CoV-2 RNA Identified through Virtual Screening

Mathez,

Brancale,

Cagno

2024

J. Chem. Inf. Model.

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We currently lack antivirals for most human viruses. In a quest for new molecules, focusing on viral RNA, instead of viral proteins, can represent a promising strategy. In this study, new inhibitors were identified starting from a published crystal structure of the tertiary SARS-CoV-2 RNA involved in the −1 programmed ribosomal frameshift. The pseudoknot structure was refined, and a virtual screening was performed using the repository of binders to the nucleic acid library, taking into consideration RNA flexibility. Hit compounds were validated against the wild-type virus and with a dualluciferase assay measuring the frameshift efficiency. Several active molecules were identified. Our study reveals new inhibitors of SARS-CoV-2 but also highlights the feasibility of targeting RNA starting from virtual screening, a strategy that could be broadly applied to drug development.

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Evaluation of otorhinolaryngologic, audiologic, and genetic findings in children with cystic fibrosis: A tertiary care experience

Nayır Büyükşahin,

Yalcın,

Gökırmak

et al. 2024

Pediatric Pulmonology

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ObjectivesTo evaluate otorhinolaryngologic findings and the relationship between aminoglycoside (AG) exposure and hearing loss in paediatric patients with cystic fibrosis (cwCF). We also aimed to investigate the genetic predisposition to AG ototoxicity by screening for m.1555A>G mutations.MethodsCwCF who underwent otorhinolaryngologic and audiologic examinations were retrospectively included. Clinical characteristics, ear‐nose‐throat related symptoms, and a history of ototoxic drug exposure were recorded. m.1555A>G mutations were retrospectively screened among patients with audiologic evaluations.ResultsTwo hundred thirty‐four cwCF were included in this study with a median age of 10.7 (range, 6.8–14.2) years. Nasal obstruction (14.1%) was the most common symptom. Fifty‐two (22.2%) patients had chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). There was a positive correlation between CRSwNP and the symptom of nasal obstruction (r:.234, p < .001), snoring (r:.179, p = .006), and sleeping with mouth open (r:.138, p = .034). One hundred forty‐nine (63.6%) patients had audiologic evaluations; 14 (9.4%) had hearing impairment. No statistical significance existed between ototoxicity and IV AG exposure (p = .90). Six (42.8%) of 14 patients did not receive ototoxic drugs. One hundred nineteen (50.8%) patients were screened for m.1555A>G mutations, and none were detected.ConclusionsAlmost a quarter of the study population had CRSwNP. Neither the relationship between AGs exposure and hearing loss nor the genetic predisposition to AG ototoxicity could be shown in cwCF.

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Aminoglycosides-Related Ototoxicity: Mechanisms, Risk Factors, and Prevention in Pediatric Patients

Cited by 7 publications

References 166 publications

Genetic Variations and Antibiotic-Related Adverse Events

Genetic Variations and Antibiotic-Related Adverse Events

Novel Inhibitors of SARS-CoV-2 RNA Identified through Virtual Screening

Evaluation of otorhinolaryngologic, audiologic, and genetic findings in children with cystic fibrosis: A tertiary care experience

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