Key Points: • The use of drills in endoscopic rhinosurgery allows for precise, safe and rapid removal of solid bone in standard procedures such as dacryo-cysto-rhinostomia and has become indispensable in complicated surgical interventions such as median maxillectomy • Conventional otologic drills are often used as they are readily available, economical and very robust in use • Injuries caused by the rotating shaft of the burr are rare yet it can represent a serious complication following drilling procedures in extended endonasal surgery • The use of low-cost, reusable otology speculum eliminated this complication of nasal entrance lacerations throughout our institution to this date • As a simple safety measurement, we can recommend the application of ear speculum as a reliable protection against drill related nasal entrance laceration

Purpose: Injuries of the nasal vestibular skin caused by the rotating burr shafts can represent a tedious complication following endonasal drilling and is experienced sooner or later by every rhino-surgeon. Material and methods: To protect the nasal entrance from laceration by the free rotating drill shaft we position an otology speculum in the nasal entrance. The speculum is held in place by the scrub nurse during the critical phase of bone drilling. Results: Following the introduction of the ear speculum protection, we successfully treated our dacryocystostamia procedures (n = 27) and median maxillectomia procedures (n = 6) without any further soft tissue erosions. Discussion: Preventive measures for injuries by endonasal drilling procedures are not reported extensively in literature. This stands in contrast to the fact that these injuries are prone to cause significant suffering as amply described in the case of nostril laceration due to nasogastric intubation or nasogastric feeding tubes. Conclusion: The use of a readily available, reusable ear speculum in endonasal drill application eliminated the complication of nasal entrance lacerations throughout our institution, hitherto.

In individuals with severe hearing loss, mobile phone communication is limited despite treatment with a cochlear implant (CI). The goal of this study is to identify the best communication practice for CI users by comparing speech comprehension of conventional mobile phone (GSM) calls, Voice over Internet Protocol (VoIP) calls, and the application of a wireless phone clip (WPC) accessory. This study included 13 individuals (mean age 47.1 ± 17.3 years) with at least one CI. Frequency response and objective voice quality were tested for each device, transmission mode and the WPC. We measured speech comprehension using a smartphone for a GSM call with and without WPC as well as VoIP-calls with and without WPC at different levels of white background noise. Frequency responses of the WPC were limited (< 4 kHz); however, speech comprehension in a noisy environment was significantly improved compared to GSM. Speech comprehension was improved by 9–27 Speech comprehension was best with VoIP alone; however, accessories such as a WPC provide additional improvement in the presence of background noise. Mobile phone calls utilizing VoIP technology, with or without a WPC accessory, result in superior speech comprehension compared to GSM.

CELL BIOLOGY Correction for “Dissociating antibacterial from ototoxic effects of gentamicin C-subtypes,” by Mary E. O’Sullivan, Yohan Song, Robert Greenhouse, Randy Lin, Adela Perez, Patrick J. Atkinson, Jacob P. MacDonald, Zehra Siddiqui, Dennis Lagasca, Kate Comstock, Markus E. Huth, Alan G. Cheng, and Anthony J. Ricci, which was first published December 7, 2020; 10.1073/ pnas.2013065117 (Proc. Natl. Acad. Sci. U.S.A. 117, 32423–32432). The authors note that reference 14 is retracted and therefore should be removed from the references list. In addition, the authors note that there is an error in the “labeling of the chemical structures of gentamicin C-subtypes.” On page 32424, right column, second full paragraph, line 1, “The C-subtypes of gentamicin differ in the C5′ and C6′ positions on ring I (Fig. 1 A and B).” should instead appear as “The C-subtypes of gentamicin differ in the C6′ position on ring I (Fig. 1 A and B).” Due to the same error, Figs. 1 and 3 appeared incorrectly. The corrected figures and their legends appear below. Lastly, the authors note that Fig. S2 in the SI Appendix appeared incorrectly because the “labeling of rings I and III was reversed.” The online version has been updated to include the updated reference list, the corrected text described above, the corrected Figs. 1 and 3, and the corrected SI Appendix.

Gentamicin is a potent broad-spectrum aminoglycoside antibiotic whose use is hampered by ototoxic side-effects. Hospital gentamicin is a mixture of five gentamicin C-subtypes and several impurities of various ranges of nonexact concentrations. We developed a purification strategy enabling assaying of individual C-subtypes and impurities for ototoxicity and antimicrobial activity. We found that C-subtypes displayed broad and potent in vitro antimicrobial activities comparable to the hospital gentamicin mixture. In contrast, they showed different degrees of ototoxicity in cochlear explants, with gentamicin C2b being the least and gentamicin C2 the most ototoxic. Structure-activity relationships identified sites in the C4'-C6' region on ring I that reduced ototoxicity while preserving antimicrobial activity, thus identifying targets for future drug design and mechanisms for hair cell toxicity. Structure-activity relationship data suggested and electrophysiological data showed that the C-subtypes both bind and permeate the hair cell mechanotransducer channel, with the stronger the binding the less ototoxic the compound. Finally, both individual and reformulated mixtures of C-subtypes demonstrated decreased ototoxicity while maintaining antimicrobial activity, thereby serving as a proof-of-concept of drug reformulation to minimizing ototoxicity of gentamicin in patients.

Facial nerve damage has a detrimental effect on a patient's life, therefore safety mechanisms to ensure its preservation are essential during lateral skull base surgery. During robotic cochlear implantation a trajectory passing the facial nerve at <0.5 mm is needed. Recently a stimulation probe and nerve monitoring approach were developed and introduced clinically, however for patient safety no trajectory was drilled closer than 0.4 mm. Here we assess the performance of the nerve monitoring system at closer distances. In a sheep model eight trajectories were drilled to test the setup followed by 12 trajectories during which the ENT surgeon relied solely on the nerve monitoring system and aborted the robotic drilling process if intraoperative nerve monitoring alerted of a distance <0.1 mm. Microcomputed tomography images and histopathology showed prospective use of the technology prevented facial nerve damage. Facial nerve monitoring integrated in a robotic system supports the surgeon's ability to proactively avoid damage to the facial nerve during robotic drilling in the mastoid.

Background Electroencephalography (EEG) studies indicate possible associations between tinnitus and changes in the neural activity. However, inconsistent results require further investigation to better understand such heterogeneity and inform the interpretation of previous findings. Objective This study aims to investigate the feasibility of EEG measurements as an objective indicator for the identification of tinnitus-associated neural activities. Methods To reduce heterogeneity, participants served as their own control using residual inhibition (RI) to modulate the tinnitus perception in a within-subject EEG study design with a tinnitus group. In addition, comparison with a nontinnitus control group allowed for a between-subjects comparison. We will apply RI stimulation to generate tinnitus and nontinnitus conditions in the same subject. Furthermore, high-frequency audiometry (up to 13 kHz) and tinnitometry will be performed. Results This work was funded by the Infrastructure Grant of the University of Bern, Bern, Switzerland and Bernafon AG, Bern, Switzerland. Enrollment for the study described in this protocol commenced in February 2018. Data analysis is currently under way and the first results are expected to be submitted for publication in 2019. Conclusions This study design helps in comparing the neural activity between conditions in the same individual, thereby addressing a notable limitation of previous EEG tinnitus studies. In addition, the high-frequency assessment will help to analyze and classify tinnitus symptoms beyond the conventional clinical standard. International Registered Report Identifier (IRRID) RR1-10.2196/12270

Introduction: Robotic cochlear implantation is a new minimally invasive approach for CI surgery. The procedure is currently evaluated in a clinical trial at the Inselspital in Bern, Switzerland. The aim of this presentation is to report preliminary clinical results of the first cases of robotic cochlear implantation. Methods: The clinical study was approved by the local IRB and regulatory body. Preoperative assessments included morphological evaluation using CT, taste examination and facial nerve neurography. During surgery, four bone fiducial screws were inserted behind the ear and CT (0.2 mm resolution) was performed to plan a drill trajectory from the mastoid surface, passing through the facial recess to the center of the round window. Access to the middle ear was drilled using a previously developed task specific image-guided robotic system. Sufficient clearance of the drill trajectory from the facial nerve was confirmed using intraoperative cone beam CT imaging. Upon completion of drilling and screw removal, a tympanomeatal flap was created and the round window membrane was exposed. An implant bed was prepared and the electrode array was manually inserted using a specifically manufactured insertion tube. Correct placement and nominal function of the implant was verified by telemetry and postoperative CT imaging. Postoperative facial nerve neurography and taste examination took place two weeks postoperatively. Audiological assessment was performed as part of routine clinical care. Results: Robotic middle ear access was completed in 4 patients, with successful electrode insertion according to the preoperatively defined plan. Audiological results for all patients are currently being collected. Conclusions: We have demonstrated in 4 patients that a CI electrode can be successfully inserted into the cochlea through a 1.8 mm keyhole access created by a surgical robot. The workflow with the robotic setup requires additional setup time and extensive teamwork.

Untersuchungsziel Der Multi-Port Ansatz fur die robotische Cochleaimplantation bietet Vorteile bezuglich Instru-mentenmanipulation und Visualisierung und eine Beruhrung von Trommelfell und Gehorkno-chelchen kann vermieden werden. In dieser Studie wurde die Machbarkeit einer minimal-invasiven Cochleaimplantation uber einen Multi-Port Zugang untersucht. Methodik In Bilddaten (CT, 0.15 x 0.15 x 0.2 mm) eines Schlafenbeinmodels (Phacon) wurden vier Trajektorien (∅ 1.8 mm, l = 21.5 bis 31.8 mm) von der Oberflache des Felsenbeins kollisions-frei zu anatomischen Strukturen zum runden Fenster geplant: retro-facial (RF), suprameatal (SM), sub-facial (SF) und durch den Rezessus Facialis (FR) und mittels eines CI-Robotersystems (Universitat Bern) realisiert. Es wurden sechs Insertionsversuche durchge-fuhrt (Visualisierung mittels EndoGnost, 0.55 mm Durchmesser, 0° Winkel, PolyDiagnost und Manipulation mit einer geraden Nadel, Medicon). Jeder Zugang bestand aus je einer Trajek-torie fur Elektrodeninsertion (immer FR), Visualisierung und Instrumentenmanipulation (Kom-bination aus RF, SM und SF). Pro Kombination wurden die endoskopisch darstellbaren sowie fur die Instrumente erreichbaren anatomischen Strukturen, die erreichte Elektrodeninserti-onstiefe und die dafur benotigte Zeit bestimmt. Anhand eines postoperativen CT wurden die Trajektorien geometrisch vermessen. Ergebnisse Der mittlere Bohrfehler betrug 0.15 mm. (SM 0.12 mm; FR 0.2 mm; RF 0.07 mm; SF 0.2 mm). Fur eine volle Insertion des Elektrodenarrays war ein Zugang bestehend aus den Trajektorien FR, RF und SF am geeignetsten (12 von 12 Elektroden innerhalb von 4:30 Minu-ten). Visualisierung und Instrumentenmanipulation via Trajektorien RF respektive SF ermog-lichten freie Sicht auf bzw. Erreichbarkeit des runden Fensters und erlaubten die zusatzliche manuelle Unterstutzung bei der Einfuhrung des Elektrodenarrays. Ein Multi-Port Zugang be-stehend aus den Trajektorien SF fur Visualisierung und RF fur Instrumentenmanipulation er-moglichte Visualisierung vieler anatomischer Strukturen, jedoch war die Trajektorie RF we-gen dem Winkel zum runden Fenster als Hilfestellung zur Elektrodeninsertion mittels eines ri-giden Instrumentes nutzlos. Die ubrigen Zugange waren mangels Visualisierung oder Er-reichbarkeit des runden Fensters ungeeignet fur eine verlassliche Insertion. Schlussfolgerung Die Moglichkeit eines Multi-Port Zugang zum runden Fenster bestehend aus drei Trajektorien ohne Beeinflussung anatomischer Strukturen konnte initial im Phantom bestatigt werden. Verschiedene Kombinationen von Zugangen wurden miteinander verglichen. Visualisierung und Manipulation durch die RF und SF verlaufenden Trajektorien ermoglichte die Darstellung und Erreichbarkeit aller zur Cochleaimplantation notigen Strukturen.

CONCLUSION:A system for robotic cochlear implantation (rCI) has been developed and a corresponding surgical workflow has been described. The clinical feasibility was demonstrated through the conduction of a safe and effective rCI procedure. OBJECTIVES:To define a clinical workflow for rCI and demonstrate its feasibility, safety, and effectiveness within a clinical setting. METHOD:A clinical workflow for use of a previously described image guided surgical robot system for rCI was developed. Based on pre-operative images, a safe drilling tunnel targeting the round window was planned and drilled by the robotic system. Intra-operatively the drill path was assessed using imaging and sensor-based data to confirm the proximity of the facial nerve. Electrode array insertion was manually achieved under microscope visualization. Electrode array placement, structure preservation, and the accuracy of the drilling and of the safety mechanisms were assessed on post-operative CT images. RESULTS:Robotic drilling was conducted with an accuracy of 0.2 mm and safety mechanisms predicted proximity of the nerves to within 0.1 mm. The approach resulted in a minimal mastoidectomy and minimal incisions. Manual electrode array insertion was successfully performed through the robotically drilled tunnel. The procedure was performed without complications, and all surrounding structures were preserved.

OBJECTIVE:The preservation of residual hearing in cochlear implantation opens the door for optimal functional results. This atraumatic surgical technique requires training; however, the traditional human cadaveric temporal bones have become less available or unattainable in some institutions. This study investigates the suitability of an alternative model, using cadaveric lamb temporal bone, for surgical training of atraumatic round window electrode insertion. INTERVENTION:A total of 14 lamb temporal bones were dissected for cochlear implantation by four surgeons. After mastoidectomy, visualization, and drilling of the round window niche, an atraumatic round window insertion of a Medel Flex24 electrode was performed. Electrode insertion depth and position were verified by computed tomography scans. MAIN OUTCOME MEASURE:All cochleas were successfully implanted using the atraumatic round window approach; however, surgical access through the mastoid was substantially different when compared human anatomy. The mean number of intracochlear electrode contacts was 6.5 (range, 4-11) and the mean insertion depth 10.4 mm (range, 4-20 mm), which corresponds to a mean angular perimodiolar insertion depth of 229 degrees (range 67-540°). Full insertion of the electrode was not possible because of the smaller size of the lamb cochlea in comparison to that of the human. CONCLUSION:The lamb temporal bone model is well suited as a training model for atraumatic cochlear implantation at the level of the round window. The minimally pneumatized mastoid as well as the smaller cochlea can help prepare a surgeon for difficult cochlear implantations. Because of substantial differences to human anatomy, it is not an adequate training model for other surgical techniques such as mastoidectomy and posterior tympanotomy as well as full electrode insertion.

Bacterial infections represent a rapidly growing challenge to human health. Aminoglycosides are widely used broad-spectrum antibiotics, but they inflict permanent hearing loss in up to ~50% of patients by causing selective sensory hair cell loss. Here, we hypothesized that reducing aminoglycoside entry into hair cells via mechanotransducer channels would reduce ototoxicity, and therefore we synthesized 9 aminoglycosides with modifications based on biophysical properties of the hair cell mechanotransducer channel and interactions between aminoglycosides and the bacterial ribosome. Compared with the parent aminoglycoside sisomicin, all 9 derivatives displayed no or reduced ototoxicity, with the lead compound N1MS 17 times less ototoxic and with reduced penetration of hair cell mechanotransducer channels in rat cochlear cultures. Both N1MS and sisomicin suppressed growth of E. coli and K. pneumoniae, with N1MS exhibiting superior activity against extended spectrum β lactamase producers, despite diminished activity against P. aeruginosa and S. aureus. Moreover, systemic sisomicin treatment of mice resulted in 75% to 85% hair cell loss and profound hearing loss, whereas N1MS treatment preserved both hair cells and hearing. Finally, in mice with E. coli-infected bladders, systemic N1MS treatment eliminated bacteria from urinary tract tissues and serially collected urine samples, without compromising auditory and kidney functions. Together, our findings establish N1MS as a nonototoxic aminoglycoside and support targeted modification as a promising approach to generating nonototoxic antibiotics.

Objective: Cochlear implants (Cl) are standard treatment for prelingually deafened children and postlingually deafened adults. Computed tomography (CT) is the standard method for postoperative imaging of the electrode position. CT scans accurately reflect electrode depth and position, which is essential prior to use. However, routine CT examinations expose patients to radiation, which is especially problematic in children. We examined whether new CT protocols could reduce radiation doses while preserving diagnostic accuracy.Methods: To investigate whether electrode position can be assessed by low-dose CT protocols, a cadaveric lamb model was used because the inner ear morphology is similar to humans. The scans were performed at various volumetric CT dose-indexes CTDIvol)/kV combinations. For each constant CTDIvol the tube voltage was varied (i.e., 80, 100, 120 and 140 kV). This procedure was repeated at different CTDIvol values (21 mGy, 11 mGy, 5.5 mGy, 2.8 mGy and 1.8 mGy). To keep the CTDIvol constant at different tube voltages, the tube current values were adjusted. Independent evaluations of the images were performed by two experienced and blinded neuroradiologists. The criteria diagnostic usefulness, image quality and artifacts (scaled 1-4) were assessed in 14 cochlear-implanted cadaveric lamb heads with variable tube voltages.Results: Results showed that the standard CT dose could be substantially reduced without sacrificing diagnostic accuracy of electrode position. The assessment of the CI electrode position was feasible in almost all cases up to a CTDIvol of 2-3 mGy. The number of artifacts did not increase for images within this dose range as compared to higher dosages. The extent of the artifacts caused by the implanted metal-containing CI electrode does not depend on the radiation dose and is not perceptibly influenced by changes in the tube voltage. Summarizing the evaluation of the CT electrode position is possible even at a very low radiation dose.Conclusions: CT imaging of the temporal bone for postoperative electrode position control of the CI is possible with a very low and significantly radiation dose. The tube current-time product and voltage can be reduced by 50% without increasing artifacts. Low-dose postoperative CT scans are sufficient for localizing the CI electrode. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

OBJECTIVES:Creation of an atraumatic, hearing-preservation cochleostomy is integral to the future of minimally invasive inner ear surgery. The goal of this study was to develop and characterize a novel chemical approach to cochleostomy. STUDY DESIGN:Prospective animal study. SETTING:Laboratory. METHODS:Experimental animal study in which phosphoric acid gel (PAG) was used to decalcify the otic capsule in 25 Hartley guinea pigs. Five animals in each of 5 surgical groups were studied: (1) mechanically opening the auditory bulla alone, (2) PAG thinning of the basal turn otic capsule, leaving endosteum covered by a layer of bone, (3) micro-pick manual cochleostomy, (4) PAG chemical cochleostomy, exposing the endosteum, and (5) combined PAG/micro-pick cochleostomy, with initial chemical thinning and subsequent manual removal of the last osseous layer. Preoperative and postoperative auditory brainstem responses and otoacoustic emissions were obtained at 2, 6, 10, and 16 kHz. Hematoxylin and eosin-stained paraffin sections were compared. RESULTS:Surgical and histologic findings confirmed that application of PAG provided reproducible local bone removal, and cochlear access was enabled. Statistically significant auditory threshold shifts were observed at 10 kHz (P = .048) and 16 kHz (P = .0013) following cochleostomy using PAG alone (group 4) and at 16 kHz using manual cochleostomy (group 3) (P = .028). No statistically significant, postoperative auditory threshold shifts were observed in the other groups, including PAG thinning with manual completion cochleostomy (group 5). CONCLUSION:Hearing preservation cochleostomy can be performed in an animal model using a novel technique of thinning cochlear bone with PAG and manually completing cochleostomy.

A 39-year-old white man presented with a swollen left upper eyelid secondary to progressive acute bacterial rhinosinusitis (ABRS). Physical examination found a 40% reduction in vision in the left eye and right-sided erythematous temporal swelling with tenderness to palpation. Computed tomography revealed the presence of an inflammatory lesion in the left orbit. Duplex ultrasonography demonstrated a thrombotic occlusion in the right superficial temporal vein (STV). For treatment of the complicated ARBS, the patient received intravenous antibiotics and underwent surgery. The STV thrombophlebitis was treated with low-molecular-weight heparin. Postoperatively, the patient recovered completely and his vision normalized; 10 days later, duplex ultrasonography showed a patent STV. The development of contralateral STV thrombophlebitis is conceivably facilitated by venous anastomoses of the scalp in the front of the head. As a result, embolic spread would be a possible complication of infectious ABRS foci communicating with intraorbital and pericranial veins. To the best of our knowledge, this is the first reported case of such a complication of ARBS in the literature.

OBJECTIVES:Sensorineural hearing loss from sound overexposure has a considerable prevalence. Identification of sound hazards is crucial, as prevention, due to a lack of definitive therapies, is the sole alternative to hearing aids. One subjectively loud, yet little studied, potential sound hazard is movie theaters. This study uses smart phones to evaluate their applicability as a widely available, validated sound pressure level (SPL) meter. Therefore, this study measures sound levels in movie theaters to determine whether sound levels exceed safe occupational noise exposure limits and whether sound levels in movie theaters differ as a function of movie, movie theater, presentation time, and seat location within the theater.DESIGN:Six smart phones with an SPL meter software application were calibrated with a precision SPL meter and validated as an SPL meter. Additionally, three different smart phone generations were measured in comparison to an integrating SPL meter. Two different movies, an action movie and a children's movie, were measured six times each in 10 different venues (n = 117). To maximize representativeness, movies were selected focusing on large release productions with probable high attendance. Movie theaters were selected in the San Francisco, CA, area based on whether they screened both chosen movies and to represent the largest variety of theater proprietors. Measurements were analyzed in regard to differences between theaters, location within the theater, movie, as well as presentation time and day as indirect indicator of film attendance.RESULTS:The smart phone measurements demonstrated high accuracy and reliability. Overall, sound levels in movie theaters do not exceed safe exposure limits by occupational standards. Sound levels vary significantly across theaters and demonstrated statistically significant higher sound levels and exposures in the action movie compared to the children's movie. Sound levels decrease with distance from the screen. However, no influence on time of day or day of the week as indirect indicator of film attendance could be found.CONCLUSIONS:Calibrated smart phones with an appropriate software application as used in this study can be utilized as a validated SPL meter. Because of the wide availability, smart phones in combination with the software application can provide high quantity recreational sound exposure measurements, which can facilitate the identification of potential noise hazards. Sound levels in movie theaters decrease with distance to the screen, but do not exceed safe occupational noise exposure limits. Additionally, there are significant differences in sound levels across movie theaters and movies, but not in presentation time.

Delivering cochlear implants through a minimally invasive tunnel (1.8 mm in diameter) from the mastoid surface to the inner ear is referred to as direct cochlear access (DCA). Based on cone beam as well as micro-computed tomography imaging, this in vitro study evaluates the feasibility and efficacy of manual cochlear electrode array insertions via DCA. Free-fitting electrode arrays were inserted in 8 temporal bone specimens with previously drilled DCA tunnels. The insertion depth angle, procedural time, tunnel alignment as well as the inserted scala and intracochlear trauma were assessed. Seven of the 8 insertions were full insertions, with insertion depth angles higher than 520°. Three cases of atraumatic scala tympani insertion, 3 cases of probable basilar membrane rupture and 1 case of dislocation into the scala vestibuli were observed (1 specimen was damaged during extraction). Manual electrode array insertion following a DCA procedure seems to be feasible and safe and is a further step toward clinical application of image-guided otological microsurgery.

Sound perception requires functional hair cell mechanotransduction (MET) machinery, including the MET channels and tip-link proteins. Prior work showed that uptake of ototoxic aminoglycosides (AG) into hair cells requires functional MET channels. In this study, we examined whether tip-link proteins, including Cadherin 23 (Cdh23), regulate AG entry into hair cells. Using time-lapse microscopy on cochlear explants, we found rapid uptake of gentamicin-conjugated Texas Red (GTTR) into hair cells from three-day-old Cdh23+/+ and Cdh23v2J/+ mice, but failed to detect GTTR uptake in Cdh23v2J/v2J hair cells. Pre-treatment of wildtype cochleae with the calcium chelator 1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA) to disrupt tip-links also effectively reduced GTTR uptake into hair cells. Both Cdh23v2J/v2J and BAPTA-treated hair cells were protected from degeneration caused by gentamicin. Six hours after BAPTA treatment, GTTR uptake remained reduced in comparison to controls; by 24 hours, drug uptake was comparable between untreated and BAPTA-treated hair cells, which again became susceptible to cell death induced by gentamicin. Together, these results provide genetic and pharmacologic evidence that tip-links are required for AG uptake and toxicity in hair cells. Because tip-links can spontaneously regenerate, their temporary breakage offers a limited time window when hair cells are protected from AG toxicity.

Aminoglycosides are commonly prescribed antibiotics with deleterious side effects to the inner ear. Due to their popular application as a result of their potent antimicrobial activities, many efforts have been undertaken to prevent aminoglycoside ototoxicity. Over the years, understanding of the antimicrobial as well as ototoxic mechanisms of aminoglycosides has increased. These mechanisms are reviewed in regard to established and potential future targets of hair cell protection.