Vestibular Hypofunction Secondary to Topical Use of Aminoglycosides in Ears with Perforated Tympanic Membrane.

INTRODUCTION: The objective of this study was to identify and clinically characterize patients treated in an Otoneurology Unit who experienced vestibular ototoxicity as a result of using aminoglycoside ear drops during outbreaks of superinfection in chronic otitis media. MATERIAL AND METHODS: An observational retrospective study was conducted, including patients with perforated eardrums who developed vestibular ototoxicity within the past 10 years following the application of topical ear aminoglycosides in a tertiary referral center. The study encompassed the assessment of the clinical presentation, treatment, quality of life, and evolution after treatment of the identified individuals. RESULTS: During the study period, 6 patients, aged between 33 and 71 years, developed vestibular ototoxicity following the use of topical aminoglycoside drops due to infection flares in chronic otitis media. All cases involved the use of gentamicin. Two cases were unilateral, and 4 were unilateral. The onset of symptoms occurred within one to four weeks of using the drops, resulting in all patients experiencing instability without vertigo attacks. After discontinuing the drops and undergoing vestibular rehabilitation, 4 patients experienced sequelae, with 2 patients (both with bilateral vestibular hypofunction) suffering significant impairment in their quality of life. CONCLUSIONS: Vestibular ototoxicity due to the topical application of aminoglycosides during acute exacerbations of chronic otitis media is a rare occurrence. However, given its potential for severe consequences and the fact that we are still encountering patients with this condition, healthcare professionals should explore alternative antibacterial agents that offer similar efficacy.

Antibiotics for acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is one of the most common diseases in childhood for which antibiotics are commonly prescribed; a systematic review reported a pooled prevalence of 85.6% in high-income countries. This is an update of a Cochrane Review first published in the Cochrane Library in 1997 and updated in 1999, 2005, 2009, 2013 and 2015. OBJECTIVES: To assess the effects of antibiotics for children with AOM. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Current Contents, CINAHL, LILACS and two trial registers. The date of the search was 14 February 2023. SELECTION CRITERIA: We included randomised controlled trials comparing 1) antimicrobial drugs with placebo, and 2) immediate antibiotic treatment with expectant observation (including delayed antibiotic prescribing) in children with AOM. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion and extracted data using the standard methodological procedures recommended by Cochrane. Our primary outcomes were: 1) pain at various time points (24 hours, two to three days, four to seven days, 10 to 14 days), and 2) adverse effects likely to be related to the use of antibiotics. Secondary outcomes were: 1) abnormal tympanometry findings, 2) tympanic membrane perforation, 3) contralateral otitis (in unilateral cases), 4) AOM recurrences, 5) serious complications related to AOM and 6) long-term effects (including the number of parent-reported AOM symptom episodes, antibiotic prescriptions and health care utilisation as assessed at least one year after randomisation). We used the GRADE approach to rate the overall certainty of evidence for each outcome of interest. MAIN RESULTS: Antibiotics versus placebo We included 13 trials (3401 children and 3938 AOM episodes) from high-income countries, which we assessed at generally low risk of bias. Antibiotics do not reduce pain at 24 hours (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.78 to 1.01; 5 trials, 1394 children; high-certainty evidence), or at four to seven days (RR 0.76, 95% CI 0.50 to 1.14; 7 trials, 1264 children), but result in almost a third fewer children having pain at two to three days (RR 0.71, 95% CI 0.58 to 0.88; number needed to treat for an additional beneficial outcome (NNTB) 20; 7 trials, 2320 children; high-certainty evidence), and likely result in two-thirds fewer having pain at 10 to 12 days (RR 0.33, 95% CI 0.17 to 0.66; NNTB 7; 1 trial, 278 children; moderate-certainty evidence). Antibiotics increase the risk of adverse events such as vomiting, diarrhoea or rash (RR 1.38, 95% CI 1.16 to 1.63; number needed to treat for an additional harmful outcome (NNTH) 14; 8 trials, 2107 children; high-certainty evidence). Antibiotics reduce the risk of children having abnormal tympanometry findings at two to four weeks (RR 0.83, 95% CI 0.72 to 0.96; NNTB 11; 7 trials, 2138 children), slightly reduce the risk of experiencing tympanic membrane perforations (RR 0.43, 95% CI 0.21 to 0.89; NNTB 33; 5 trials, 1075 children) and halve the risk of contralateral otitis episodes (RR 0.49, 95% CI 0.25 to 0.95; NNTB 11; 4 trials, 906 children). However, antibiotics do not reduce the risk of abnormal tympanometry findings at six to eight weeks (RR 0.89, 95% CI 0.70 to 1.13; 3 trials, 953 children) and at three months (RR 0.94, 95% CI 0.66 to 1.34; 3 trials, 809 children) or late AOM recurrences (RR 0.94, 95% CI 0.79 to 1.11; 6 trials, 2200 children). Severe complications were rare, and the evidence suggests that serious complications do not differ between children treated with either antibiotics or placebo. Immediate antibiotics versus expectant observation We included six trials (1556 children) from high-income countries. The evidence suggests that immediate antibiotics may result in a reduction of pain at two to three days (RR 0.53, 95% CI 0.35 to 0.79; NNTB 8; 1 trial, 396 children; low-certainty evidence), but probably do not reduce the risk of pain at three to seven days (RR 0.75, 95% CI 0.50 to 1.12; 4 trials, 959 children; moderate-certainty evidence), and may not reduce the risk of pain at 11 to 14 days (RR 0.91, 95% CI 0.75 to 1.10; 1 trial, 247 children; low-certainty evidence). Immediate antibiotics increase the risk of vomiting, diarrhoea or rash (RR 1.87, 95% CI 1.39 to 2.51; NNTH 10; 3 trials, 946 children; high-certainty evidence). Immediate antibiotics probably do not reduce the proportion of children with abnormal tympanometry findings at four weeks and evidence suggests that immediate antibiotics may not reduce the risk of tympanic membrane perforation and AOM recurrences. No serious complications occurred in either group. AUTHORS' CONCLUSIONS: This review reveals that antibiotics probably have no effect on pain at 24 hours, a slight effect on pain in the days following and only a modest effect on the number of children with tympanic perforations, contralateral otitis episodes and abnormal tympanometry findings at two to four weeks compared with placebo in children with AOM. In high-income countries, most cases of AOM spontaneously remit without complications. The benefits of antibiotics must be weighed against the possible harms: for every 14 children treated with antibiotics, one child experienced an adverse event (such as vomiting, diarrhoea or rash) that would not have occurred if antibiotics were withheld. For most children with mild disease in high-income countries, an expectant observational approach seems justified. Therefore, clinical management should emphasise advice about adequate analgesia and the limited role for antibiotics.

Complications and prognosis associated with intra-tympanic steroid injection to treat sudden sensorineural hearing impairment.

PURPOSE: The purpose of this study was to measure the incidence of complications in sudden sensorineural hearing loss (SSNHL) patients treated with intra-tympanic steroid injection (ITSI) and compare hearing recovery rates. MATERIALS AND METHODS: 123 patients with unilateral SSNHL receiving ITSIs were included in this study. Post-ITSI complications were documented including otalgia, dysgeusia, vertigo (duration>1 h), and persistent eardrum perforation. The pain intensity was evaluated with visual analog scale (VAS). Hearing was measured before ITSI and at 1 month after the final ITSI. We compared our patients' hearing threshold between presence and absence of different complications. RESULTS: 47.2% patients experienced post-injection otalgia with the average VAS score 3.2 (range 2-6). Five (4.1%) and six (4.9%) patients exhibited vertigo and persistent eardrum perforations, respectively. The patients were divided into three groups based on the absence of complications and the presence of vertigo and eardrum perforation. The hearing threshold improvements did not differ significantly among the three groups (p = 0.366). Although the difference was not significant (p = 0.664), the proportion of patients experiencing post-ITSI vertigo who were on contemporaneous oral steroids was lower than the proportion of non-vertigo patients on such steroids. CONCLUSION: The incidences of otalgia, vertigo, and persistent eardrum perforation in SSNHL patients treated with ITSI were 47.2%, 4.1% and 4.9%, respectively. We found no association between concurrent oral steroid use and the incidence of post-ITSI eardrum perforation or vertigo. Although statistical significance was lacking, patients who did not take contemporaneous oral steroids may have a higher rate of prolonged post-ITSI vertigo.

Triangulation of pharmacoepidemiology and laboratory science to tackle otic quinolone safety.

BACKGROUND: The scientific method requires studies with high internal and external validity. Though both are necessary, they do not go hand-in-hand: The more controlled a study is to enhance internal validity, the less applicable to real-world clinical care, and vice versa. In the many instances where evidence from clinical trials is not available, scientific inference must rely on more extreme approaches on this spectrum, such as mechanistic (limited generalizability/strong bias control) and real-world evidence (RWE) studies (higher generalizability/lesser bias control). OBJECTIVES: Illustrate how triangulating mechanistic and RWE studies can enhance scientific inference by delivering the supporting evidence for both. METHODS: We describe our research on an unexpected and highly unlikely drug safety issue: the risk of tympanic membrane (TM) perforations resulting from otic quinolone therapy. Tightly controlled laboratory studies using cell culture and rodent models were complemented with pharmacoepidemiological studies of real-world data to translate mechanistic findings and corroborate RWE. RESULTS: We present a cascade of mechanistic and RWE studies investigating fibroblast cytotoxicity, delayed healing of perforated TMs, and spontaneous TM perforations after otic quinolone exposure, all suggesting local tissue toxicity. CONCLUSION: Triangulation of mechanistic and RWE studies allowed incremental progress toward robust evidence on otic quinolone toxicity.

Commercial Quinolone Ear Drops Cause Perforations in Intact Rat Tympanic Membranes.

HYPOTHESIS: Commercial quinolone ear drops may promote the development of perforations (TMPs) in intact tympanic membrane (TMs). BACKGROUND: Quinolone ear drops have been associated with TMPs after myringotomy +/- tube placement in a drug-specific manner and potentiation by steroids. METHODS: Rats were randomized to six groups (10/group), with one ear receiving otic instillation of dexamethasone, ofloxacin, ciprofloxacin, ofloxacin + dexamethasone, ciprofloxacin + dexamethasone, or neomycin + polymyxin + hydrocortisone-all commercial formulations and at standard clinical concentrations-and the contralateral ear receiving saline, twice daily for 10 days. TMs were assessed over 42 days. RESULTS: No TMPs were seen in ears treated with saline, dexamethasone, or neomycin. At day 10, TMPs were seen in one of 10 ofloxacin- and three of 10 ciprofloxacin + dexamethasone-treated ears (p = 0.038). At day 14, the ofloxacin TMP healed. In contrast, the three ciprofloxacin + dexamethasone TMPs remained and one new TMP developed in this group. A ciprofloxacin and an ofloxacin + dexamethasone-treated ears also had TMPs (p = 0.023). By day 21, the ofloxacin + dexamethasone TMP and two of four of the ciprofloxacin + dexamethasone TMPs healed but two new TMPs were seen in ciprofloxacin + dexamethasone ears (p = 0.0006). At day 28, 1 of 10 ciprofloxacin and 4 of 10 ciprofloxacin + dexamethasone-treated ears had TMPs (p = 0.0006). By day 35, only one ciprofloxacin + dexamethasone had TMP (p = 0.42). All TMPS were healed at day 42. CONCLUSIONS: Application of commercial quinolone ear drops can cause TMPs in intact TMs. This effect appears to be drug-specific and potentiated by steroids.

Is Pool Water Disinfectant (Hydrogen Peroxide-Silver Composition) Ototoxic in Rats?

OBJECTIVES: The purpose of our study was to evaluate whether hydrogen peroxide and silver composition (H202-Ag) used in pool water disinfectant is ototoxic to individuals with tympanic membrane perforation. MATERIALS AND METHODS: The tympanic membranes of both ears of 14 Wistar-type albino female rats were perforated. Since topical application was performed, the right and left ears were categorized as two subgroups (a: right ear, b: left ear). Baseline auditory brainstem response (ABR) was measured. The groups were classified according to topical applications performed as Ia (30 mg/L H202-Ag), Ib (saline), IIa (70 mg/L H202-Ag), and IIb (saline). The topical applications were performed for 30 min/day for 10 days. The ABR was measured 24 hours after the last application, and the animals were sacrificed. Bilateral temporal bones were examined using light microscopy. RESULTS: An apparent rise in the hearing thresholds of the groups Ia and Ib was not observed. However, there was an apparent rise in the hearing thresholds of the group IIa, which supports ototoxicity. According to histopathology results, there weren't any pathological findings in groups Ia and Ib and did not display special features, but a neurotoxic effect was observed in group II. CONCLUSION: Our study shows that the H202-Ag used in pool water disinfection can have ototoxic and neurotoxic effects, particularly at high concentrations.

Mixed hearing loss in iatrogenic tympanic membrane perforations over the round window niche and the immediate effect of paper patch myringoplasty.

OBJECTIVES: Report the immediate audiologic effect of paper patch myringoplasty to repair iatrogenic tympanic membrane perforations directly over the round window. METHODS: Retrospective case-control study of 15 patients treated for inner ear disease with a MicroWick and dexamethasone for 1 month, resulting in 2-mm perforations over the round window. Paper patch myringoplasties were performed to repair the perforations. Audiograms were performed before and immediately after the paper patch myringoplasty. RESULTS: After paper patch placement, there was a significant improvement in air-bone gap at 250 (p < 0.001), 500 (p = 0.003), and 1000 Hz (p = 0.004) and a significant improvement in bone conduction (BC) threshold at 250 (p = 0.002), 500 (p < 0.001), 1000 (p = 0.002), 2000 (p = 0.003), and 3000 Hz (p = 0.02). CONCLUSIONS: Paper patch myringoplasty improves both air conduction and BC hearing from small perforations over the round window. The decrease in BC hearing is a result of middle ear mechanics and is not a true sensorineural hearing loss.

Ototoxic effect of topical ciclopirox as an antimycotic preparation.

OBJECTIVE: To evaluate the ototoxicity of ciclopirox-containing solution as an otologic preparation for the treatment of otomycosis. BACKGROUND: Ciclopirox is a synthetic antimycotic agent available in a variety of formulations to treat superficial fungal infections. Ciclopirox has demonstrated both fungicidal and fungistatic activity in vitro against a broad spectrum of pathogenic fungi. It also possesses a broad-spectrum antibacterial properties, anti-inflammatory, and antiedema effect. The ototoxic effect of ciclopirox-containing solutions has not been known, so the current study was designed to observe the ototoxic effect of this solution experimentally. MATERIALS AND METHODS: Experiments were performed in 22 young male albino guinea pigs (weight, 450-550 g). The 10 animals in the experimental group received ciclopirox solution, and the control group was divided into two groups of six animals each. The first group received saline solution (negative control) and the second received gentamicin (40 mg/mL; ototoxic control). Under general anesthesia, pretreatment auditory brainstem responses (ABRs) from the right ears were obtained from the animals in all groups. The right tympanic membranes were totally perforated, and a small piece of Gelfoam was applied to the middle ear directly to the round window membrane. Ear solutions were applied through transcanal approach to the middle ear twice a day in 2 weeks. Twenty-two animals of perforated tympanic membrane were observed during a 2-week period. Posttreatment ABRs were obtained in all groups in a week after the last administration. RESULTS: Baseline ABR results were normal in right ears of all animals tested. Animals undergoing placement of Gelfoam with either ciclopirox solution or saline in the middle ear showed no changes in the ABR threshold. The gentamicin group showed a significant change in the ABR threshold. CONCLUSION: In the guinea pig, when applied topically to the middle ear, ciclopirox does not cause a reduction in the ABR threshold. Because its safety has not yet been confirmed in patients, caution should be observed when prescribing this agent.

The effect of naproxen sodium on experimental otitis media.

OBJECTIVES: We evaluated the effect of naproxen sodium on propylene glycol-induced otitis media in guinea pig ears. MATERIALS AND METHODS: Twenty adult guinea pigs were randomized to the study and control groups equal in number. A single dose of propylene glycol (0.2 ml, 60%) was applied to the left ears of the control group and to both ears of the study group. Saline solution was applied to the right ears of the control group. After propylene glycol application, the study group received naproxen sodium (oral, 10 mg/kg daily) for 15 days, whereas the control ears were left untreated. At the end of four weeks, the animals were decapitated under anesthesia. Otoscopic examination was performed and temporal bones were removed for histologic examination under light microscopy. RESULTS: Nine animals were alive in each group at the end of four weeks. In the control group, all the right ears receiving saline solution were normal, whereas otitis media and inflammatory changes were observed in six of the left ears receiving propylene glycol. In the study animals treated with naproxen sodium, otitis media and tympanic membrane perforation were seen in 14 ears. Of these, three ears had purulent, 11 ears had serous effusion. Epithelial hyperplasia (n=10), keratinizing epithelium and cholesteatoma formation (n=4) were also observed. CONCLUSION: Our results suggest that the administered dose of systemic naproxen sodium has no inhibitory effect on the development of inflammation and otitis media.

Chronic tympanic membrane perforation: a better animal model is needed.

Developments in the treatment of chronic tympanic membrane perforation have been hindered by the lack of an ideal animal model. It is not appropriate to test such treatments on acute perforations as the majority of these heal spontaneously. An ideal animal model would be one that most closely resembles the human clinical situation. It should be inexpensive, readily available, and easy to create. There have been a number of attempts to create a chronic tympanic membrane perforation model with limited success. All published attempts at chronic tympanic membrane perforations have been reviewed and the limitations of each model are discussed. A number of areas for research exist for further developing a chronic tympanic membrane perforation model. These areas include a perforation model in the presence of bacteria and eustachian tube dysfunction. Understanding the molecular and genetic mechanisms of chronic otitis media and potential treatments will also be useful.

Tympanic membrane breakdown after intratympanic injection of steroids in irradiated ears.

OBJECTIVE: To describe a rare complication of intratympanic injection of steroids in susceptible ears. PATIENTS: We present two patients with a history of irradiation involving the injected ear. INTERVENTION: Therapeutic. MAIN OUTCOME MEASURE: Tympanic membrane condition after intratympanic injection of steroids. RESULTS: Total or near-total breakdown of the irradiated tympanic membrane. CONCLUSION: Tympanic membranes with an impaired wound-healing ability, together with exposure to intratympanic steroids, may be at risk for total or near-total breakdown.

Creating a stable tympanic membrane perforation using mitomycin C.

OBJECTIVE: To determine the ability of topically applied mitomycin C to create a stable tympanic membrane perforation. STUDY DESIGN AND SETTING: Twenty-four rats underwent subtotal removal of the tympanic membranes bilaterally. Forty ears received 0.2 mg/ml of mitomycin C. The remaining 8 received phosphate-buffered saline solution (control). Photographs taken every 3 to 5 days for 44 days were digitally scanned and computer analyzed to calculate the percentage of residual perforation. Application of solutions, photography, and data analysis were performed in a blinded fashion. RESULTS: The mitomycin C treated ears had delayed closure time and healing rate (from day 0 to 25) compared to the control group. All controls healed by day 14. By day 44, 92.5% of the mitomycin C treated ears healed. CONCLUSION: Mitomycin C prolongs the closure and healing rate of myringotomies in rat tympanic membranes. SIGNIFICANCE: Myringotomy with concurrent mitomycin C application may be useful for creating an animal model for chronic tympanic membrane perforation and should be tested in human beings as a method to maintain myringotomy patency for long-term ventilation.

Tympanic membrane rupture following general anesthesia with nitrous oxide: a case report.

Although rare, tympanic membrane rupture during general anesthesia with nitrous oxide has been reported previously in the literature. Nitrous oxide administration and the effects on closed body cavities will be reviewed. Key factors in patient assessment which can determine safe use of nitrous oxide in the clinical setting will also be discussed.