Why are ototopical aminoglycosides still first-line therapy for chronic suppurative otitis media? A systematic review and discussion of aminoglycosides versus quinolones

Harris, Andrew; Elhassan, H A; Flook, Evelyn

doi:10.1017/s0022215115002509

Cited by 16 publications

(15 citation statements)

References 42 publications

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“…The potential for such medications to reach the inner ear is dependent on various factors, such the presence of middle ear discharge, mucosal thickness, and round window membrane permeability. Nonetheless, they are frequently assumed by physicians to be safe as long as they are used in sub-damaging doses [Harris et al, 2016]. The results of this study suggest that such an assumption may not hold true if the ear were to be exposed to irradiation and gentamicin at the same time.…”

Section: Discussionmentioning

confidence: 77%

Synergistic Ototoxicity of Gentamicin and Low-Dose Irradiation: Molecular Basis and Clinical Significance

2019

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Background: Inner ear structures may be included in the radiation fields when irradiation is used to treat patients with head and neck cancers. These patients may also have concurrent infections that require gentamicin treatment. Radiation and gentamicin are both potentially ototoxic, and their combined use has been shown to result in synergistic ototoxicity in animals. Objective: We aimed to confirm the synergistic ototoxicity of combined gentamicin and low-dose irradiation treatment and identify the underlying molecular mechanisms using an in vitro model. Method: We compared the ototoxic effects of gentamicin, low-dose irradiation, and their combination in the OC-k3 mouse cochlear cell line using cell viability assay, live/dead stain, apoptosis detection assay, oxidative stress detection, and studied the molecular mechanisms involved using immunoblot analysis. Results: Combined treatment led to prolonged oxidative stress, re-duced cell viability, and synergistic apoptosis. Gentamicin induced the concurrent accumulation of LC3b-II and SQSTM1/p62, suggesting an impairment of autophagic flux. Low-dose irradiation induced transient p53 phosphorylation and persistent Akt phosphorylation in response to DNA damage. In combined treatment, gentamicin attenuated irradiation-induced Akt activation. Conclusions: Besides increased oxidative stress, synergistic apoptosis observed in combined treatment could be attributed to gentamicin-induced perturbation of autophagic flux and attenuation of Akt phosphorylation, which led to an impairment of radiation-induced DNA repair response.

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Section: Discussionmentioning

confidence: 77%

Synergistic Ototoxicity of Gentamicin and Low-Dose Irradiation: Molecular Basis and Clinical Significance

2019

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“…There are numerous papers discussing the topical use of ciprofloxacin, a closely related drug, in mice (Kavanagh et al ), guinea pigs (Brownlee et al ) and humans (Ozagar et al , Kutz et al , Samarei ). Results from these studies suggest it is a very safe drug when used topically in OM; in fact, current opinions in human otology are that fluoroquinolones are safer than aminoglycosides when used topically and should be considered as first‐line drugs for OM (Harris et al ). The results from this study would concur with that view.…”

Section: Discussionmentioning

confidence: 99%

Brainstem auditory evoked responses in 37 dogs with otitis media before and after topical therapy

Paterson¹

2017

J of Small Animal Practice

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OBJECTIVES : The objective of this study was to determine whether intra-aural administration of aqueous solutions of marbofloxacin, gentamicin, tobramycin and ticarcillin (used off-licence) was associated with changes in hearing as measured by brainstem auditory evoked responses.MATERIALS AND METHODS : Dogs diagnosed with otitis media (n=37) underwent brainstem auditory evoked response testing and then were treated for their ear disease. First, the external ear canal and middle ear were flushed with sterile saline followed by EDTA tris with 0·15% chlorhexidine. Then, a combination of aqueous antibiotic mixed with an aqueous solution of EDTA tris was instilled into the middle ear.Follow-up examinations were undertaken for each dog, and treatment was continued until there were no detected infectious organisms or inflammatory infiltrate. Brainstem auditory evoked response testing was repeated after resolution of the infection and discontinuation of therapy.RESULTS : Brainstem auditory evoked responses in dogs treated with aqueous solutions of marbofloxacin or gentamicin remained unchanged or improved after therapy of otitis media but were impaired in dogs treated with ticarcillin or tobramycin.CLINICAL SIGNIFICANCE : If off-licence use of topical antibiotics is deemed necessary in cases of otitis media, aqueous solutions of marbofloxacin and gentamicin appear to be less ototoxic than aqueous solutions of ticarcillin or tobramycin.

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“…Clinically, topical treatment of OM with aminoglycosides, such as neomycin, is effective, but also controversial and many otolaryngologists are concerned that aminoglycoside eardrops may be ototoxic if they enter the middle ear through a ruptured tympanic membrane (TM) 10 . Scientific evidence for this specific concern is scarce and clinicians often take precaution and best practice, avoiding the ototopical use of aminoglycosides.…”

Section: Introductionmentioning

confidence: 99%

Intratympanic Lipopolysaccharide Elevates Systemic Fluorescent Gentamicin Uptake in the Cochlea

Chai

Yang

et al. 2021

The Laryngoscope

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Objectives/Hypothesis Lipopolysaccharide (LPS), a key component of bacterial endotoxins, activates macrophages and triggers the release of inflammatory cytokines in mammalian tissues. Recent studies have shown that intratympanic injection of LPS simulates acute otitis media (AOM) and results in morphological and functional changes in the inner ear. Here we established an AOM mouse model with LPS to investigate the uptake of ototoxic gentamicin in the inner ear, and elucidated the underlying mechanism by focusing on cochlear inflammation as a result of AOM. Study Design Preclinical rodent animal model. Methods Fluorescently tagged gentamicin (GTTR) was systemically administered to mice with AOM. Iba1‐positive macrophage morphology and inner ear cytokine profile were evaluated by immunofluorescence technique and a mouse cytokine array kit, respectively. Results We observed characteristic symptoms of AOM in the LPS‐treated ears with elevated hearing thresholds indicating a conductive hearing loss. More importantly, the LPS‐induced AOM activated cochlear inflammatory responses, manifested by macrophage infiltration, particularly in the organ of Corti and the spiral ligament, in addition to the up‐regulation of proinflammatory cytokines. Meanwhile, GTTR uptake in the stria vascularis and sensory hair cells from all the LPS‐treated ears was significantly enhanced at 24, 48, and 72‐hour post‐treatment, as the most prominent enhancement was observed in the 48‐hour group. Conclusion In summary, this study suggests that the pathological cochlea is more susceptible to ototoxic drugs, including aminoglycosides, and justified the clinical concern of aminoglycoside ototoxicity in the AOM treatment. Laryngoscope, 131:E2573–E2582, 2021

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Why are ototopical aminoglycosides still first-line therapy for chronic suppurative otitis media? A systematic review and discussion of aminoglycosides versus quinolones

Cited by 16 publications

References 42 publications

Synergistic Ototoxicity of Gentamicin and Low-Dose Irradiation: Molecular Basis and Clinical Significance

Synergistic Ototoxicity of Gentamicin and Low-Dose Irradiation: Molecular Basis and Clinical Significance

Brainstem auditory evoked responses in 37 dogs with otitis media before and after topical therapy

Intratympanic Lipopolysaccharide Elevates Systemic Fluorescent Gentamicin Uptake in the Cochlea

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