Microbiome and Otic Quinolone Levels Following Tympanoplasty Assessed by Gelatin Sponge Analysis.

OBJECTIVE: To determine if absorbable gelatin sponge (AGS) can be used to assess the posttympanoplasty microbiome and otic antibiotic exposure. STUDY DESIGN: Prospective. SETTING: Tertiary hospital. METHODS: Patients undergoing tympanoplasty were prospectively enrolled. Intraoperatively, AGS was applied to the medial ear canal/tympanic membrane (TM) for 1 minute after canal incision, then saved for analysis. Ear canals were packed with AGS at the end of surgery. Otic ofloxacin was administered until the first postoperative visit, when AGS was collected. Microbial presence was assessed by culture. Ofloxacin levels were assessed by liquid-chromatography mass-spectrometry. RESULTS: Fifty-three patients were included. AGS was collected in 92.9% of patients seen within 21 days compared to 70.8% of those seen at 22 to 35 days. At surgery, AGS yielded bacteria and fungi in 81% and 11%, respectively, including Staphylococcus species (55%) and Pseudomonas species (25%). Postoperatively, AGS yielded bacteria in 71% and fungi in 21% at the meatus, (staphylococci 57% and pseudomonas 25%). TM samples yielded bacteria in 69%, fungi in 6%, staphylococci in 53%, and pseudomonas in 19%. Ofloxacin concentration at the meatus was 248 µg/mL (95% confidence interval [CI]: 119-377) and at the TM was 126 µg/mL (95% CI: 58-194). Ofloxacin-resistant colonies were found in 75% of patients. CONCLUSION: Analysis of AGS is a viable technique for noninvasively studying healing metrics posttympanoplasty, including the microbiome and otic antibiotic exposure. Despite exposure to a high concentration of quinolones, the tympanoplasty wound is far from sterile, which may impact healing outcomes.

Potential Toxicity of Boric Acid Powder Otic Insufflation.

OBJECTIVE: Boric acid (BA) powder is commonly used to treat otologic conditions, such as mastoid bowl inflammation and chronic otitis externa. Exposure to 50 mg per day is thought to cause systemic toxicity in humans. Inflamed skin and mucosal surfaces readily absorb BA. The aim of this study was to measure the doses of BA commonly used in clinical otology and alert the otolaryngology community to BA's underappreciated potential source of systemic toxicity. STUDY DESIGN: Prospective, controlled. SETTING: Laboratory. METHODS: BA dose administration was measured by weighing the BA generated by common insufflators: accordion bellows, House-Sheehy insufflator, DeVilbiss insufflator, and pneumatic powder blower. Manual insufflation was performed with 3 compressions of the bulb. The pneumatic blower was sprayed for 1 second. Measurements were repeated 10 times. RESULTS: The DeVilbiss insufflator delivered the lowest mean BA dose, 6.1 mg (SD 3.4, range 2.1-13.7), followed by the House-Sheehy 8.9 mg (SD 8.4, range 1.6-27.8), the pneumatic blower 192.8 mg (SD 38.3, range 150.0-261.7), and the accordion, 284.1 mg (SD 215.0, range 37.8-730.8). CONCLUSION: BA dose delivery is highly variable by insufflator type, and doses thought to cause systemic toxicity are commonly generated. Awareness of and further investigation into the potential toxicity of otic administration of BA seems warranted.

American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Foundation Guide to Enhance Otologic and Neurotologic Care During the COVID-19 Pandemic.

: This combined American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Surgery Foundation document aims to provide guidance during the coronavirus disease of 2019 (COVID-19) on 1) "priority" of care for otologic and neurotologic patients in the office and operating room, and 2) optimal utilization of personal protective equipment. Given the paucity of evidence to inform otologic and neurotologic best practices during COVID-19, the recommendations herein are based on relevant peer-reviewed articles, the Centers for Disease Control and Prevention COVID-19 guidelines, United States and international hospital policies, and expert opinion. The suggestions presented here are not meant to be definitive, and best practices will undoubtedly change with increasing knowledge and high-quality data related to COVID-19. Interpretation of this guidance document is dependent on local factors including prevalence of COVID-19 in the surgeons' local community. This is not intended to set a standard of care, and should not supersede the clinician's best judgement when managing specific clinical concerns and/or regional conditions.Access to otologic and neurotologic care during and after the COVID-19 pandemic is dependent upon adequate protection of physicians, audiologists, and ancillary support staff. Otolaryngologists and associated staff are at high risk for COVID-19 disease transmission based on close contact with mucosal surfaces of the upper aerodigestive tract during diagnostic evaluation and therapeutic procedures. While many otologic and neurotologic conditions are not imminently life threatening, they have a major impact on communication, daily functioning, and quality of life. In addition, progression of disease and delay in treatment can result in cranial nerve deficits, intracranial and life-threatening complications, and/or irreversible consequences. In this regard, many otologic and neurotologic conditions should rightfully be considered "urgent," and almost all require timely attention to permit optimal outcomes. It is reasonable to proceed with otologic and neurotologic clinic visits and operative cases based on input from expert opinion of otologic care providers, clinic/hospital administration, infection prevention and control specialists, and local and state public health leaders. Significant regional variations in COVID-19 prevalence exist; therefore, physicians working with local municipalities are best suited to make determinations on the appropriateness and timing of otologic and neurotologic care.

Prevalence of occult cochlear basal turn patency.

BACKGROUND: Perilymph gusher (PLG) is a rare complication of otologic surgery attributed to a communication between the cochlea and the internal auditory canal (IAC). Subtle patency between the cochlear basal turn and IAC has recently been identified on computed tomography (CT) as a risk factor, specifically when the defect is > 0.75 mm. OBJECTIVES: Investigate the prevalence of radiographic cochlear basal turn patency. MATERIALS AND METHODS: Patients with CT of the temporal bones and inner ears interpreted as "normal" were included. An otologist and a radiologist independently reviewed CTs to measure radiographic dehiscence in an oblique plane along the interface of the cochlea and IAC. Known PLGs were excluded. RESULTS: Two hundred and ten ears were included (88 conductive or mixed hearing loss, 62 sensorineural hearing loss, 41 audiometrically normal ears). 71 ears (33.8%) were radiographically patent. Mean defect width was 0.41 mm (0.15-0.7 mm). Defect width was not associated with type of hearing loss, age, or gender. No defects were wider than 0.75 mm. CONCLUSIONS: Radiographic patency of the cochlear basal turn may be present in patients with hearing loss and normal hearing, but patency > 0.75 mm (i.e. risk for PLG) is rare.

Rat Model of External Auditory Canal Stenosis.

HYPOTHESIS: Circumferential electrocautery injury of the rat external auditory canal (EAC) can induce a reproducible animal model of acquired stenosis. BACKGROUND: Acquired EAC stenosis may occur as a result of chronic inflammation or trauma to the EAC skin and is characterized by narrowing of the EAC, retention of debris, and hearing loss. Treatment is surgery but it is often complicated by restenosis. A reliable and inexpensive animal model of EAC stenosis has not been described. There have been no studies correlating the extent of EAC injury with the extent of stenosis. METHODS: Rats received a 25, 50, or 75% circumferential EAC injury with electrocautery. The extent of resulting stenosis was quantified 21 days following injury. The nature of the injury and healing response was assessed with histology. RESULTS: A 25% circumferential injury led to 4 to 34% stenosis (mean, 13%), 50% injury resulted in 43 to 100% stenosis (mean, 73%), and 75% injury resulted in 94 to 100% stenosis (mean=99%, p < 0.0001). The 50% circumferential injury produced 30 to 75% stenosis in five of eight ears, the remainder had >75% stenosis. Wounded ears showed evidence of intact cartilage and epithelium, with increased thickness of the subepithelial layer and localized fibrosis. CONCLUSIONS: Electrocautery injury in the ventral aspect of the rat EAC resulted in reproducible EAC stenosis. This rat model may be useful in studying therapy to prevent acquired EAC stenosis due to acute injury. The correlation of the extent of injury (circumference) with resulting stenosis may inform clinical management of EAC injuries.

Clinical Practice Guideline: Ménière's Disease.

OBJECTIVE: Ménière's disease (MD) is a clinical condition defined by spontaneous vertigo attacks (each lasting 20 minutes to 12 hours) with documented low- to midfrequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. It also presents with fluctuating aural symptoms (hearing loss, tinnitus, or ear fullness) in the affected ear. The underlying etiology of MD is not completely clear, yet it has been associated with inner ear fluid (endolymph) volume increases, culminating in episodic ear symptoms (vertigo, fluctuating hearing loss, tinnitus, and aural fullness). Physical examination findings are often unremarkable, and audiometric testing may or may not show low- to midfrequency sensorineural hearing loss. Conventional imaging, if performed, is also typically normal. The goals of MD treatment are to prevent or reduce vertigo severity and frequency; relieve or prevent hearing loss, tinnitus, and aural fullness; and improve quality of life. Treatment approaches to MD are many and typically include modifications of lifestyle factors (eg, diet) and medical, surgical, or a combination of therapies. PURPOSE: The primary purpose of this clinical practice guideline is to improve the quality of the diagnostic workup and treatment outcomes of MD. To achieve this purpose, the goals of this guideline are to use the best available published scientific and/or clinical evidence to enhance diagnostic accuracy and appropriate therapeutic interventions (medical and surgical) while reducing unindicated diagnostic testing and/or imaging.

Clinical Practice Guideline: Ménière's Disease Executive Summary.

OBJECTIVE: Ménière's disease (MD) is a clinical condition defined by spontaneous vertigo attacks (each lasting 20 minutes to 12 hours) with documented low- to midfrequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. It also presents with fluctuating aural symptoms (hearing loss, tinnitus, or ear fullness) in the affected ear. The underlying etiology of MD is not completely clear, yet it has been associated with inner ear fluid volume increases, culminating in episodic ear symptoms (vertigo, fluctuating hearing loss, tinnitus, and aural fullness). Physical examination findings are often unremarkable, and audiometric testing may or may not show low- to midfrequency sensorineural hearing loss. Imaging, if performed, is also typically normal. The goals of MD treatment are to prevent or reduce vertigo severity and frequency; relieve or prevent hearing loss, tinnitus, and aural fullness; and improve quality of life. Treatment approaches to MD are many, and approaches typically include modifications of lifestyle factors (eg, diet) and medical, surgical, or a combination of therapies. PURPOSE: The primary purpose of this clinical practice guideline is to improve the quality of the diagnostic workup and treatment outcomes of MD. To achieve this purpose, the goals of this guideline are to use the best available published scientific and/or clinical evidence to enhance diagnostic accuracy and appropriate therapeutic interventions (medical and surgical) while reducing unindicated diagnostic testing and/or imaging.

The Effects of Steroids on Survival of Mouse and Human Tympanic Membrane Fibroblasts.

OBJECTIVE: Tympanic membrane (TM) fibroblast cytotoxicity of quinolone ear drops is enhanced by dexamethasone and fluocinolone. Hydrocortisone has not been evaluated. We aimed to assess the effects of these 3 steroids on mouse and human TM fibroblast survival. STUDY DESIGN: In vitro. SETTING: Academic laboratory. SUBJECTS AND METHODS: Mouse and human TM fibroblasts were exposed to hydrocortisone, dexamethasone, or fluocinolone at concentrations in commercial ear drops (1%, 0.1%, or 0.025%, respectively) and at steroid potency equivalents (1%, 0.033%, or 0.0033%, respectively), or dilute ethanol (control), twice within 24 hours or 4 times within 48 hours for 2 hours each time. Cells were observed with phase-contrast microscopy until the cytotoxicity assay was performed. RESULTS: Mouse and human TM fibroblasts treated with any of the steroids had lower survival after 24 and 48 hours compared to control (all P < .0001). After 24 hours, viability of mouse fibroblasts treated with the steroids was not different (P > .05), while treatment with hydrocortisone decreased human TM fibroblast viability (P < .0001). After 48 hours, at concentrations found in ear drops and at equivalent steroid potency, dexamethasone and fluocinolone had similar survival in mouse and human fibroblasts (all P > .05), but hydrocortisone had lower survival in both mouse (P = .02 and P < .0001) and human (P < .0001) fibroblasts. Phase-contrast images mirrored the cytotoxicity findings. CONCLUSION: Steroids found in commercial ear drops reduce survival of mouse and human TM fibroblasts. Hydrocortisone appears to be more cytotoxic than the more potent steroids, dexamethasone and fluocinolone. These findings should be considered when assessing clinical outcomes of ototopical preparations.

Appropriateness of Otic Quinolone Use among Privately Insured US Patients.

OBJECTIVE: Considering emerging safety concerns involving otic quinolones, we assessed the extent of otic quinolone use for questionable indications. STUDY DESIGN: Descriptive cross-sectional study of a national sample of privately insured patients. SETTING: Outpatient encounters in the United States. SUBJECTS AND METHODS: Children and adults with outpatient pharmacy-dispensing claims for new prescriptions of otic or ophthalmic quinolones in 2017 were identified within the IBM MarketScan Commercial Claims & Encounters and the Medicare Supplemental Database. Each dispensing ≥30 days apart constituted a unique episode. Only claims with supporting ear-related diagnoses on outpatient encounters ±3 days of dispensing were considered. Ophthalmic drops were excluded if eye-related diagnoses were found ±30 days. Prescribing was classified as appropriate, questionable, or undetermined. RESULTS: We found 214,897 episodes in 200,270 patients. Adults were twice as likely as children to have otic treatment with questionable indications (6.2% vs 3.0%). Sensitivity analyses with broader time windows to ascertain diagnoses showed similar proportions of questionable use. Otalgia and cerumen impaction constituted 90% of questionable indications. Family physicians (6.8%) and internists (8.0%) had higher percentages of questionable use than other specialties. CONCLUSION: Based on the demonstrated risks of quinolone ear drops, opportunities exist to decrease otic quinolone use, especially in adults.

Cytotoxicity of Ear Drop Excipients in Human and Mouse Tympanic Membrane Fibroblasts.

OBJECTIVE: Commercial ear drops contain ingredients reported to be inactive. We sought to evaluate such excipients for possible cytotoxicity on human and mouse tympanic membrane (TM) fibroblasts. STUDY DESIGN: Prospective, in vitro. SETTING: Tertiary academic center. SUBJECTS AND METHODS: Mouse and human TM fibroblasts were treated with 1:10 dilutions of benzalkonium chloride (BKC) 0.0025%, 0.006%, or 0.01%; benzyl alcohol 0.9%; polysorbate 80 (PSB) 2.5%; glycerin 2.4%; povidone 0.2%; or water (control), twice within 24 hours or 4 times within 48 hours, for 2 hours each time. Cells were placed back in growth media after the treatments. Cells were observed with phase-contrast microscopy until the cytotoxicity assay was performed. RESULTS: Mouse fibroblasts had lower survival in only the PSB-treated cells compared to the control (P < .0001) after 24 hours. After 48 hours, PSB killed nearly all mouse fibroblasts (P < .0001). BKC decreased fibroblast survival in a dose-dependent manner (P < .001). In human TM fibroblasts, all excipients except povidone and benzyl alcohol after 24 hours and povidone after 48 hours reduced cell survival compared to control (P = .012 to P < .0001). The cytotoxicity of BKC in human TM fibroblasts was also dose dependent (<.0001). PSB was less cytotoxic to human fibroblasts. Phase-contrast images mirrored the cytotoxicity findings. CONCLUSION: Polysorbate 80 and benzalkonium chloride, at concentrations found in commercial ear drops, may be cytotoxic to human and mouse TM fibroblasts. "Inactive" ingredients may need to be considered when evaluating clinical outcomes with commercial ear drops.

Prophylactic antibiotics in head and neck free flap surgery: A novel protocol put to the test.

OBJECTIVE: Recent evidence supports the use of ampicillin-sulbactam as a favored choice for antibiotic prophylaxis following head and neck free flap reconstructive surgery. However, there is a paucity of evidence guiding the optimal duration of antibiotic prophylaxis. The aim of this study is to compare the infection rates of short courses of ampicillin-sulbactam versus extended courses of various antibiotics in head and neck free flap reconstructive surgery. METHODS: This is a retrospective cohort study conducted from 2012 to 2017 at a tertiary academic center on 266 consecutive patients undergoing head and neck surgery with free flap reconstruction. The primary outcome measure was the rate of any infection within 30 days of surgery. RESULTS: There were 149 patients who received antibiotic prophylaxis for an extended duration of at least seven days. 117 patients received a short course of antibiotics defined as 24 h for non-radiated patients and 72 h for radiated patients. Postoperative infections occurred in 45.9% of patients, of which 92.6% occurred at surgical sites. There was no significant difference in terms of postoperative infection rate between patients receiving an extended duration of antibiotics versus a short duration (p = 0.80). This held true for subgroups of surgical site infections (p = 0.38) and distant infections (p = 0.59 for pneumonia and p = 0.76 for UTI). Risk factors for infections were identified as hypothyroidism (p = 0.047) and clean contaminated wound classification (p = 0.0002). CONCLUSION: Shorter duration of ampicillin-sulbactam prophylaxis in free flap reconstruction of head and neck defects does not negatively affect postoperative infection rates. LEVEL OF EVIDENCE: Level 2b.

Microbiome Analysis of Cholesteatoma by Gene Sequencing.

OBJECTIVE: To compare the microbial flora of cholesteatoma and normal middle ears using gene-based sequencing analysis. STUDY DESIGN: Controlled ex vivo human study. SETTING: Academic, tertiary medical center. SUBJECTS AND METHODS: Brush, swab, and tissue samples were each taken from cholesteatoma matrix and uninvolved tissue in patients with previously untreated, acquired cholesteatoma (n = 19) or middle ear mucosa from patients undergoing cochlear implantation with no history of cholesteatoma or previous middle ear surgery (control; n = 12). DNA was isolated from specimens then 16S rRNA gene sequencing was performed. RESULTS: There was no difference in microbial yield between the sampling methods. Cholesteatoma specimens had lower relative abundance of 14 bacterial species compared with controls including Acidovorax sp., Bacillus sp., Masillia sp., Moraxella osloensis, Phenylobacterium conjunctum, Sphingomonas sp., and Staphylococcus epidermidis (all p < 0.05). Alternaria sp. were present on nearly all the specimens. Alternaria sp. and Cladosporium herbarum (both p ≤ 0.05) were lower in the cholesteatoma compared with control group. There was no difference in the relative abundance of any bacteria or fungi between the cholesteatoma matrix and uninvolved middle ear mucosa. CONCLUSIONS: Microbiome of cholesteatoma matrix is largely similar to adjacent mucosa. This differs from healthy ears. Further study is needed to understand if middle ear microbiome may impact cholesteatoma pathogenesis or treatment.

Cochlear basal turn patency in unrecognized perilymph gushers.

OBJECTIVES: Perilymph gusher (PLG), an uncommon complication of otologic surgery, has been attributed to communication between the cochlea and the internal auditory canal (IAC). Subtle osseous defects may be missed on routine review of computed tomography (CT). This study aimed to quantify cochlear basal turn patency not seen on axial CT in patients with PLG and compare those against patients without intraoperative PLG. METHODS: Ears that underwent cochlear implantation or stapedotomy with preoperative helical CT that was interpreted as "normal" at a tertiary referral center. An otologist and a radiologist independently and in a blinded fashion measured the dimensions of cochlear basal turn patency on CT images in oblique plane and parasagittal planes along the interface of the cochlea and IAC fundus. RESULTS: Sixty-one ears were reviewed, including 3 with surgically confirmed PLGs and 12 with apparent dehiscence without a PLG. Mean defect width with PLG was 0.83 mm (range 0.75-0.9 mm) and without PLG was 0.43 mm (range 0.3-0.65 mm, p = 0.011). A greater proportion of PLGs occurred in ears with defects (3 of 15) than in ears without (0 of 46, p = 0.013). Using a cutoff of 0.75 mm, a greater proportion of PLGs occurred with defect width >0.75 mm (3 of 3) than in defects <0.75 mm (0 of 12, p = 0.022). CONCLUSIONS: CT dehiscence between the IAC and cochlear basal turn, particularly with a width > 0.75 mm, should be considered a risk for PLG with stapedotomy or cochlear implantation.

Novel Computed Tomography Findings Suggestive of Perilymph Gusher.

OBJECTIVES: Perilymphatic gusher (PLG) is an uncommon complication of stapedectomy and cochlear implant placement. Computerized tomography (CT) may reveal congenital dysplasia responsible for PLG but may also be (incorrectly) interpreted as normal. The aim of this study was to review CT findings in patients with PLG reported to have normal temporal bones. PATIENTS: Patients in which a PLG was encountered and preoperative CT imaging had been interpreted as normal. INTERVENTION: Collaborative review of temporal bone computed tomography by neurotologist and neuroradiologist. MAIN OUTCOME MEASURE: Identification of undetected inner ear anomalies that may predispose to PLG. RESULTS: Unanticipated PLG was encountered during stapes surgery in two patients and cochlear implantation in one. A focal bony dehiscence between the basal turn of the cochlea and internal auditory canal (IAC) was identified on a few oblique reformatted images in all patients. CONCLUSIONS: High resolution CT with oblique image reformatting is essential to identify focal communication between the IAC and basal turn of the cochlea in ears with PLG.

Effects of Common Ear Drops on Tympanic Membrane Healing in Rats.

Objective Ciprofloxacin + dexamethasone ear drops have been associated with higher rates of tympanic membrane perforations than ofloxacin. This was thought to be an effect of the steroid; however, ciprofloxacin (sans steroid) has been found to be more toxic to tympanic membrane fibroblasts than ofloxacin in vitro. This study aimed to compare the effect of these agents on tympanic membrane healing in vivo. Study Design Controlled animal study. Setting Academic research laboratory. Methods Perforations were created in 54 rats with a carbon dioxide laser. Rats were randomized to 6 groups (9/group), with 1 ear receiving ofloxacin, ciprofloxacin, dexamethasone, ofloxacin + dexamethasone, ciprofloxacin + dexamethasone, or neomycin, and the contralateral ear receiving saline twice daily for 10 days. Healing was assessed over 40 days. Results Ofloxacin did not delay healing relative to saline. All other treatments delayed healing relative to ofloxacin at day 10 ( P < .0001). Dexamethasone and ofloxacin + dexamethasone delayed healing up to day 14 ( P < .0001). Neomycin and ciprofloxacin + dexamethasone further delayed healing up to day 28 ( P = .009) and day 35 ( P = .043), respectively. All eardrums healed by day 10 with ofloxacin, day 20 with ciprofloxacin, day 28 for dexamethasone, and day 35 for ofloxacin + dexamethasone. At day 40, 2 of 9 ciprofloxacin + dexamethasone-treated eardrums had not healed. All saline-treated eardrums in the ofloxacin, ciprofloxacin, dexamethasone, and ofloxacin + dexamethasone groups were healed by day 14, but this was delayed to day 20 in the ciprofloxacin + dexamethasone group ( P = .007). Conclusions Ototopical quinolones delay rat tympanic membrane healing in a drug-specific manner, with ciprofloxacin having a greater impact than ofloxacin. This effect is potentiated by steroids.

Prevention and Management of Complications in Otosclerosis Surgery.

Surgical management of otosclerosis is a relatively safe and effective procedure, with a high rate of hearing improvement and a low rate of undesirable outcomes and complications. Many of these potential complications are common to any middle ear surgery, but many are unique to surgery involving the stapes footplate. Preventing complications with stapes surgery and minimizing their impact may be achieved by preparation as well as surgical experience.

Cytotoxicity of Ciprofloxacin and Steroids in Mouse Tympanic Membrane Fibroblasts.

Objective Ciprofloxacin, commonly given as eardrops, has been shown to adversely affect tympanic membrane fibroblasts. Dexamethasone potentiates this effect. A newly available eardrop contains ciprofloxacin and fluocinolone, a more potent steroid. We evaluated the cytotoxic effects of this preparation on mouse tympanic membrane fibroblasts. Study Design Prospective, in vitro. Setting Academic laboratory. Subjects and Methods In experiment 1, fibroblasts were exposed to 1:10 dilutions of commercially available 0.3% ofloxacin, 0.3% ciprofloxacin, 0.3% ciprofloxacin + 0.1% dexamethasone, 0.3% ciprofloxacin + 0.025% fluocinolone, or dilute hydrochloric acid (control), twice within 24 hours. In experiment 2, cells were also treated with the dilutions of the pure form of dexamethasone 0.1% or fluocinolone 0.025%, alone and in combination with ofloxacin or ciprofloxacin. Cells were exposed to the solutions for 2 hours each time and were placed back in growth media after the treatments. Cells were observed with phase-contrast microscope until the cytotoxicity assay was performed. Results Survival of fibroblasts treated with ofloxacin was not different from the control. Fibroblasts treated with ciprofloxacin, ciprofloxacin + dexamethasone, or ciprofloxacin + fluocinolone had much lower survival (all P < .0001). Cells treated with ciprofloxacin + fluocinolone had lower survival than ciprofloxacin ( P < .0001) and ciprofloxacin + dexamethasone ( P = .0001). Steroids alone also decreased fibroblast survival compared to control ( P < .0001). The combination of dexamethasone or fluocinolone with ciprofloxacin, but not ofloxacin, further decreased fibroblast survival ( P < .0001). Phase-contrast images mirrored the cytotoxicity findings. Conclusion Tympanic membrane fibroblast cytotoxicity of ciprofloxacin is potentiated by corticosteroids. This effect may be deleterious when treating a healing perforation but beneficial when treating granulation tissue on the tympanic membrane.

Mitochondria-Targeted Antioxidant Mitoquinone Reduces Cisplatin-Induced Ototoxicity in Guinea Pigs.

Objective To determine if mitoquinone (MitoQ) attenuates cisplatin-induced hearing loss in guinea pigs. Study Design Prospective and controlled animal study. Setting Academic, tertiary medical center. Subjects and Methods Guinea pigs were injected subcutaneously with either 5 mg/kg MitoQ (n = 9) or normal saline (control, n = 9) for 7 days and 1 hour before receiving a single dose of 10 mg/kg cisplatin. Auditory brainstem response thresholds were measured before MitoQ or saline administration and 3 to 4 days after cisplatin administration. Results Auditory brainstem response threshold shifts after cisplatin treatment were smaller by 28 to 47 dB in guinea pigs injected with MitoQ compared with those in the control group at all tested frequencies (4, 8, 16, and 24 kHz, P = .0002 to .04). Scanning electron microscopy of cochlear hair cells showed less outer hair cell loss and damage in the MitoQ group. Conclusion MitoQ reduced cisplatin-induced hearing loss in guinea pigs. MitoQ appears worthy of further investigation as a means of preventing cisplatin ototoxicity in humans.