Janus mesoporous organosilica/platinum nanomotors for active treatment of suppurative otitis media.

We report a Janus mesoporous organosilica/platinum (MOS/Pt) nanomotor for active targeted treatment of suppurative otitis media, as a new type of multi-functional ear drop. The efficient propulsion of MOS/Pt nanomotors in hydrogen peroxide ear-cleaning drops significantly improves their binding efficiency with Staphylococcus aureus and enhances their antibacterial efficacy.

Tympanomastoidectomy versus parenteral antibiotic therapy for pediatric otorrhea.

OBJECTIVE: To evaluate the efficacy of tympanomastoidectomy versus parenteral antibiotic therapy for otorrhea as a result of chronic suppurative otitis media (CSOM) without cholesteatoma in the pediatric population. METHODS: A retrospective review of 221 patients treated for otorrhea at a tertiary academic pediatric hospital was performed to evaluate the impact of tympanomastoidectomy versus parenteral antibiotic therapy on resolution of otorrhea. Inclusion criteria were age 0-18 years, prior treatment with otic and/or oral antibiotic, prior history of tympanostomy tube placement for recurrent otitis media, history of otorrhea, treatment with tympanomastoidectomy or parenteral antibiotic therapy, and follow-up of at least 1 month after intervention. Time to resolution was compared between the two modalities adjusting for age, bilateral ear disease status, and comorbidities using a Cox proportional hazard model. RESULTS: Eighty-three ears from 58 children met the inclusion criteria. Ears that initially underwent tympanomastoidectomy had a significantly shorter time to resolution of symptoms (median time to resolution) 9 months (95 % confidence interval CI: 6.2-14.8) vs. 48.5 months (95 % lower CI 9.4, p = 0.006). On multivariate analysis, however, only bilateral ear disease status was independently associated with time to resolution of symptoms (hazard ratio 0.4, 95 % CI 0.2-0.9, p = 0.03). There was no statistically significant difference in the rate of treatment-related complications when comparing tympanomastoidectomy to parenteral antibiotic therapy (p = 0.37). CONCLUSION: When adjusting for age, bilateral ear disease status, and comorbidities, there does not appear to be a significant difference in time to resolution of symptoms when comparing parenteral antibiotic therapy to tympanomastoidectomy. An informed discussion regarding risks and benefits of each approach should be employed when deciding on the next step in management for patients with CSOM who have failed more conservative therapies.

Bacteriological Profile and Drug Susceptibility in Mucosal type Chronic Suppurative Otitis Media.

BACKGROUND: In Chronic Suppurative Otitis Media, mucosal type, most common organisms are Pseudomonas aeruginosa and Proteus species (P. mirabilis and P. vulgaris). It is important to prescribe culture-directed antibiotics to prevent resistance. This study was conducted to determine the bacteriological profile and drug susceptibility in patient with chronic suppurative otitis media. METHODS: This is a hospital-based descriptive study done at Gandaki Medical College, Pokhara, Nepal from July 2019 to June 2020. Under aseptic condition, the swab specimens were obtained from patients with history of ear discharge of >12 weeks duration and findings central perforation of the tympanic membrane. The sample was labeled and immediately transferred to the microbiology lab for culture/sensitivity test according to the guidelines of the Clinical and Laboratory Standards Institute. RESULTS: Out of total 127 patients, 48 (37.8%) were male and 79 (62.2%) were female. One hundred and seven samples (84.3%) had positive culture while 20 samples (15.7%) had no growth. Staphylococcus aureus (43%), was the most common isolate followed by Pseudomonas aeruginosa (23.4%), Proteus mirabilis (9.3%), and Escherichia coli (8.4%). All the organisms isolated were 100% sensitive to imipenem followed by 96.2% sensitive to gentamicin and 95.3% to amikacin. CONCLUSIONS: Staphylococcus aureus (43%) was the most predominant isolate followed by Pseudomonas aeruginosa (23.4%), Proteus mirabilis (9.3%), and Escherichia coli (8.4%). Imipenem was the most sensitive antibiotic (100%) followed by gentamicin (96.2%), amikacin (95.3%), and ofloxacin (88.78%).

Positive pressure therapy for Ménière's disease.

BACKGROUND: Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. It is often treated with medication, but different interventions are sometimes used. Positive pressure therapy is a treatment that creates small pressure pulses, generated by a pump that is attached to tubing placed in the ear canal. It is typically used for a few minutes, several times per day. The underlying cause of Ménière's disease is unknown, as is the way in which this treatment may work. The efficacy of this intervention at preventing vertigo attacks, and their associated symptoms, is currently unclear. OBJECTIVES: To evaluate the benefits and harms of positive pressure therapy versus placebo or no treatment in people with Ménière's disease. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 September 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in adults with a diagnosis of Ménière's disease comparing positive pressure therapy with either placebo or no treatment. We excluded studies with follow-up of less than three months.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) change in hearing, 6) change in tinnitus and 7) other adverse effects. We considered outcomes reported at three time points: 3 to < 6 months, 6 to ≤ 12 months and > 12 months. We used GRADE to assess the certainty of evidence for each outcome.  MAIN RESULTS: We included three studies with a total of 238 participants, all of which compared positive pressure using the Meniett device to sham treatment. The duration of follow-up was a maximum of four months.  Improvement in vertigo A single study assessed whether participants had an improvement in the frequency of their vertigo whilst using positive pressure therapy, therefore we are unable to draw meaningful conclusions from the results.  Change in vertigo Only one study reported on the change in vertigo symptoms using a global score (at 3 to < 6 months), so we are again unable to draw meaningful conclusions from the numerical results. All three studies reported on the change in the frequency of vertigo. The summary effect showed that people receiving positive pressure therapy had, on average, 0.84 fewer days per month affected by vertigo (95% confidence interval from 2.12 days fewer to 0.45 days more; 3 studies; 202 participants). However, the evidence on the change in vertigo frequency was of very low certainty, therefore there is great uncertainty in this estimate.   Serious adverse events None of the included studies provided information on the number of people who experienced serious adverse events. It is unclear whether this is because no adverse events occurred, or whether they were not assessed and reported.  AUTHORS' CONCLUSIONS: The evidence for positive pressure therapy for Ménière's disease is very uncertain. There are few RCTs that compare this intervention to placebo or no treatment, and the evidence that is currently available from these studies is of low or very low certainty. This means that we have very low confidence that the effects reported are accurate estimates of the true effect of these interventions. Consensus on the appropriate outcomes to measure in studies of Ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area and enable meta-analyses of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits.

Mapping of audiometric analysis with microbiological findings in patients with chronic suppurative otitis media (CSOM): a neglected clinical manifestation.

Otitis media (OM) is an umbrella term for a number of conditions associated with middle ear inflammation. Chronic suppurative otitis media (CSOM), a type of OM, is characterized by long-term middle ear infection with perforated ear drum and otorrhea. The most common outcome associated with it is acquired hearing impairment in infected individuals which ultimately affects their cognitive and scholastic developments. Clinically, CSOM is thought to be a sequel of re-occurring episodes of Acute otitis media (AOM). Pseudomonas aeruginosa and Staphylococcus aureus are found to be the predominant pathogenic isolates in these patients. However, with the emergence of antibiotic resistance amongst these pathogens, the adequate evaluation and treatment of this condition has become more problematic. The disease has also been recognized as one of the neglected tropical clinical manifestations with high prevalence in school-age children, especially in poor or underprivileged countries. Moreover, untreated cases have further worsened the situation by contributing to various life-threatening complications. Thus, effective treatment and surgical strategies, as well as strengthening of hearing care algorithms along with the discovery of novel animal models for advanced clinical research, can jointly help to fight this disease. In this regard, mapping of the audiological analysis with microbiological findings in CSOM patients may help elucidate the frequency that favors growth of specific pathogens. Knowledge about this potential correlation can then support timely detection of the infection, which is perceived as one of the emerging approaches for its management. In addition to these strategies, creating a true sense of awareness among people can also help mitigate this pathological condition by facilitating early identification, prevention, and treatment. This review discusses the incidence, pathogenesis, investigations, complications, and available treatment modalities associated with CSOM.

Efficacy and safety of 1.5% levofloxacin otic solution for the treatment of otitis media in a multicenter, randomized, double-blind, parallel-group, placebo-controlled, phase III study.

OBJECTIVE: The present study aimed to evaluate the efficacy and safety of 1.5% levofloxacin (LVFX) otic solution for the treatment of patients with otitis media. METHODS: This multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 trial was conducted at 34 institutions in Japan. A total of 202 patients with chronic suppurative otitis media (CSOM) or acute otitis media (AOM) were randomized into either the LVFX group or placebo group. A total of 6-10 drops of 1.5% otic solution of LVFX or its matching placebo were administered in the diseased ear twice daily, in the morning and evening for up to 10 days. Images corresponding to three clinical findings-purulent otorrhea, hyperemia (redness), and granulation tissue formation in the middle ear and tympanic membrane-for each diseased ear were evaluated using digital endoscopy by a blinded central independent review committee (BICRC) at each visit after treatment administration. RESULTS: In total, the data of 201 participants (LVFX group, 99; placebo group, 102) were analyzed. The proportion of patients with disappearance (improvement rate) of all three clinical findings at the end of treatment or discontinuation by the BICRC was 46.5% (46/99) in the LVFX group and 23.5% (24/102) in the placebo group, and the difference (95% confidence interval) between the groups was 22.0% (8.7, 34.2), with a significantly higher improvement rate in the LVFX group than in the placebo group (p = 0.001; Cochran-Mantel-Haenszel test), demonstrating the efficacy of LVFX. The bacterial eradication rates were 93.9% (77/82) and 12.5% (11/88) in the LVFX and placebo groups, respectively, and the rate was significantly higher in the LVFX group than in the placebo group (p < 0.001). Treatment-related adverse events (AEs) occurred in 5.1% (5/99) and 7.8% (8/102) of the patients in the LVFX and placebo groups, respectively, and no significant difference was noted in incidence rate between the groups. CONCLUSION: The clinical efficacy of 1.5% LVFX otic solution for CSOM and AOM was demonstrated by the resolution of inflammation in the middle ear and tympanic membrane as well as through the high bacterial eradication rate observed. No deaths or serious treatment-related AEs were observed. The study provided confirmation that 1.5% LVFX otic solution is a safe, well-tolerated, and effective treatment for CSOM and AOM.

Antibiogram and molecular characterization of extended-spectrum ß-lactamase-producing pathogens implicated in chronic suppurative otitis media.

Introduction: beta-lactamase-producing bacteria, especially extended-spectrum beta-lactamase (ESBL) producers have strong clinical relevance and have been implicated in chronic suppurative otitis media (CSOM) treatment failures. This study aimed to determine the frequency, antibiogram, and molecular characteristics of ESBL-producing gram-negative bacterial (GNB) pathogens isolated from patients with CSOM. Methods: three hundred (300) ear swab samples collected from patients with active CSOM were analysed using standard microbiological techniques. Antibiogram of pathogens was determined by Kirby-Bauer disk diffusion technique. Phenotypic detection and molecular characterization of ESBL-producing GNB pathogens were performed by double disk synergy test (DDST) and polymerase chain reaction (PCR). Results: Escherichia coli and P. aeruginosa were more prevalent among CSOM patients with a duration of discharge >2 weeks. The frequency of ESBL producers among the GNB pathogens was 18.3%. Isolates were generally multidrug-resistant but very susceptible (100% - 70.4%) to ciprofloxacin, imipenem, and amikacin. Multiple antibiotic resistance values of the isolates ranged from 0.7-0.8. Polymerase chain reaction showed that blaSHV (47.6%) was the most predominant ESBL genotype. This was followed by blaTEM (25.2%) and blaCTX-M (10.7%) as the least predominant ESBL gene. Concomitant expression of ESBL gene was observed in 13.6% of the isolates. Conclusion: this study reported the occurrence and spread of ß-lactamase-producing bacteria in patients with CSOM infections. It is therefore very crucial to screen for antibiotic-resistant pathogens at early stages of CSOM infections, for proper antimicrobial therapy and to curb the increasing spread of antimicrobial resistance.

Povidone-Iodine Fails to Eradicate Chronic Suppurative Otitis Media and Demonstrates Ototoxic Risk in Mice.

HYPOTHESIS: Commercially available povidone-iodine solution can eliminate biofilms and persister cells rapidly in in vivo achievable concentrations without inducing ototoxicity. BACKGROUND: Chronic suppurative otitis media (CSOM) is a substantial global problem. Current treatment options often induce a temporary remission without leading to a permanent cessation of symptoms secondary to the treatments' inability to eliminate persister cells. Povidone-iodine has been shown to be able to clear biofilm and planktonic cells in in vitro assays, but there are reports of ototoxic effects limiting its clinical utility. METHODS: Bacterial and biofilm growth with quantification by spectrophotomer, murine auditory brainstem response (ABR), and distortion product otoacoustic emissions, immunohistochemistry, in vivo povidone-iodine treatment of murine CSOM, persister cell assay. RESULTS: Commercially available 10% povidone-iodine solution is able to completely eradicate multiple clinical strains of Pseudomonas aeruginosa and Staphylococcus aureus in vitro with 10 minutes of exposure. Mice that have received a transtympanic injection of 1% povidone-iodine solution did not have significantly different auditory brainstem response or distortion product otoacoustic emission results compared with the control. Mice that received a povidone-iodine scrub or 10% povidone-iodine solution had significantly worsened hearing (25- and 13-dB increase in threshold, respectively; p < 0.05). In vivo CSOM infection recurred in all mice after the completion of treatment with 10% povidone-iodine solution, and there was no improvement in the bacterial load after treatment, indicating in vivo failure of therapy. CONCLUSION: Povidone-iodine solution is effective at eliminating biofilm and persister cells in vitro at in vivo achievable concentrations but fails in vivo most likely because of kinetics of distribution in vivo. Even if drug distribution could be improved, the therapeutic window is likely to be too small given that the diluted solution does not have ototoxic potential, whereas while the scrub variant, which contains detergents, and the undiluted solution are ototoxic after a single treatment.

Antibiogram guided optimized medical treatment in chronic otitis media: A useful interventional strategy before surgery?

BACKGROUND: Chronic otitis media is a middle ear cleft disease presenting with tympanic membrane perforation and discharge. Wet ear after tympanoplasty and discharging mastoid cavity are problematic in clinical practice. MATERIAL AND METHODS: 1050 patients of age 10 to 50 years presenting with active ear discharge and clinically diagnosed with unilateral chronic suppurative otitis media were included in the study. The patients were equally divided into two equal groups, Group ET, and AT. All patients were prescribed topical ciprofloxacin, oral levocetirizine 5 mg and n-acetyl cysteine 600 mg BD for one week. Swabs of ear discharge were collected in ET groups for antibiogram. Both groups were evaluated on next visit and treatment changed in AT groups and result observed in next visit. Surgical outcome was evaluated at end of 2 yrs. RESULT: A total of 1158 organisms were isolated in culture out of which, 69.94 % were aerobes, 13.47 % anaerobes and 16.58 % were fungi. On the second visit in group AT, treatment of 85.14 % patients was changed in accordance with culture sensitivity report. In patients with mucosal disease, only 46.87 % patients of group ET had a favorable outcome in comparison to 90.28 % patients of group AT while in patients with squamosal disease, 17.56 % patients of group ET and 28.99 % patients in group AT had a dry ear. Surgeries in AT group were found to have statistically significant higher success rate as compared to ET group.

Definite therapy of mixed infection alleviates refractory dilemma of adult chronic suppurative otitis media.

The characteristics, risk factors, microbial distributions and effective treatment regimens for Chronic suppurative otitis media (CSOM) patients intractable to empirical therapy were analyzed. Adult CSOM patients of China Medical University Hospital from 2018 to 2020 were included. Subjects of refractory and non-refractory groups were investigated for characteristics of age, sex, nation, comorbidities, otomycosis, and associated complications. Risk factors, microbiology distributions, and treatment regimens were analyzed. Twenty-six refractory patients (55.0 ± 17.7 years) and 66 non-refractory patients (54.1 ± 13.7 years) were studied. A significantly higher rate of otomycosis and CSOM complications was observed in refractory group than in non-refractory one (73.1% vs. 36.4%; p = 0.002; 57.7% vs. 10.6%, p < 0.001, respectively). Multivariate analysis revealed atopic diathesis (p = 0.048), otomycosis (p = 0.003) and CSOM complications (p < 0.001) were risk factors of refractory CSOM. Coagulase-negative staphylococci (CoNS) and methicillin-resistant Staphylococcus aureus (MRSA) were the prevailing pathogens. Patients of refractory group tented to have higher rates of mixed infection (42.9%% vs. 23.7%) and significantly more included fungal pathogen (19.0% vs. 2.6%; p = 0.049) than those of non-refractory cohort. Topical treatment of fungus significantly improved outcome of refractory CSOM. Atopic diathesis, otomycosis, and CSOM-associated complications were risk factors of refractory CSOM. Systemic and local treatment to possible drug-resistant pathogens, likely CoNS and fungus, possible improves recalcitrant CSOM. Correspondingly, early identification of CSOM complications, routine culture and susceptibility testing and treatment of resistant bacteria and fungus are key elements to the successful management of adult CSOM.

A contemporary overview on the enigma of managing recalcitrant or intractable post-operative otorrhoea following middle-ear surgery: perspectives, principles and practices.

BACKGROUND: A common problem in otological surgeries is the persistence of ear discharge in a patient who has undergone middle-ear reconstructive surgery, despite an intact graft. There is a dearth of knowledge in the literature on treatment strategies in such post-operative cases of recalcitrant otorrhoea. METHOD: This was a retrospective observational descriptive study conducted on 45 patients who fitted the criteria for recalcitrant post-operative otorrhoea. All 45 patients showed no response to conservative treatment for 14 days from onset of discharge. Therefore, these patients were then given antiseptic ear drops. RESULTS: Thirty patients out of 45 showed a good response to antiseptic ear drops and achieved a dry ear at the end of the treatment. CONCLUSION: In patients with recalcitrant otorrhoea with or without granulations after middle-ear reconstruction surgery, this study found that topical antiseptic ear drops, particularly those using boric acid powder, are more effective than topical antibiotic drops.

Effects of ciprofloxacin or co-amoxicillin with and without antidepressants on behavioral deficit in rats induced with chronic suppurative otitis media.

Chronic suppurative otitis media (CSOM) is chronic infection of middle ear which is usually managed with antibiotic therapy. This infection may cause the depression and cognitive changes in patients. The aim of present study was to evaluate the effect of antibiotic (ciprofloxacin and co-amoxicillin) with antidepressant or without antidepressants (bromazepam and imipramine) at low doses on rats with induced with CSOM. Pseudomonas aeruginosa was used to induce CSOM by in rat ear (tympanic bulla). The rats were divided into eight groups having six animals in each group. Neuropharmacological activities and gross behavior were observed in open field activity, force swimming cage, maze test, light and dark activity box and traction test. Observations were noted weekly after the administration of ciprofloxacin (15.3mg/kg), co-amoxicillin (15.3mg/kg), imipramine (1.15mg/kg) and bromazepam (0.09mg/kg) intraperitoneally. The altered behavior and depression was observed in control positive but reverted back in groups maintained on antidepressants with antibiotics with significant improved locomotor activity, memory in memory cage, muscular co-ordination and body balance and decreased anxiety. On the other hand, groups treated with only antibiotics showed significant improvement only in force swimming and traction test at day 14. Therefore, the antidepressant effects of the drugs can be employed to attenuate stress and depression in patients with CSOM.

Hepatotoxicity induced by chronic suppurative otitis media in rats and effects of ceftazidime and amikacin on it.

Chronic suppurative otitis media (CSOM) is the chronic inflammation with perforation of middle ear. If CSOM is not treated, it may cause secondary inflammation of liver with elevated liver enzymes and histological changes. Present study is aimed to observe the hepatotoxic effects due chronic suppurative otitis media (CSOM) in CSOM induced rats and alsoto observe the effects of ceftazidime and amikacin to attenuate hepatotoxicity due to CSOM. Liver enzyme tests and histological examinations were performed on rats divided into different groups as G1 (negative control), G2 (positive control), G3 ceftizidime (15mg/kgintraperitonelly) and G4 amikacin (15mg/kg). One-way ANOVA showed that liver enzymes were significantly increased (p=0.000 and F value 6.899) except gamma glutamic transferase in G2 (rats with CSOM without treatment) from G1 (negative control without CSOM) with histological damage of liver. These hepatotoxic effects were attenuated or recover with proper treatment with potent antibiotics (ceftazidime and amikacin). Therefore, study showed that chronic suppurative otitis media can induce hepatic toxicity including elevated liver enzymes level and inflammation, aggregation or infiltration in liver cells in rat model with reversible hepatic damage. If CSOM is treated with adult dose of ceftazidime or amikacin, it may attenuate the damage and prevent risk of liver damage.

Accuracy and patient perceived difficulty of utilizing ototopical antibiotic therapy.

PURPOSE: To examine how patients self-administer ear drops, ascertain their perceived difficulty in performing the task and determine if they are able to deliver the correct dosage. MATERIALS AND METHODS: This is a prospective cohort study performed in an otology outpatient clinic with twenty-one subjects with a condition requiring ototopical antibiotics. The number of ear drops applied as well as skills performed during ear drop application was measured. Patient reported difficulty and confidence in application of ear drops data was also obtained. RESULTS: The mean number of drops applied was 2.91 ± 2.1 (target = 3 drops) with a large variance in drop application, range of 0.6 to 9.2 drops. If "correct dosage" is considered 85-115% of the intended dose, then almost half of patients, 47.6%, underdosed with 23.8% that over dosed. Patients reported that the average difficulty in applying drops to themselves was 3.6 (1 being easy and 10 being difficult). Patients reported a high confidence level in applying the correct dose of ear drops of 6.7 (1 being not confident and 10 being very confident). CONCLUSIONS: In our study of 21 patients self-administering ear drops, only 28.6% of patients were able to correctly apply the appropriate treatment dose, with almost half of patients underdosing. Questionnaire data indicated that most patients were unaware they were administering an incorrect dose. Inaccurate administration of ear drops could be problematic and lead to longer durations of symptoms, false treatment failures, and increased costs.

Topical Therapy Failure in Chronic Suppurative Otitis Media is Due to Persister Cells in Biofilms.

OBJECTIVE: Chronic suppurative otitis media (CSOM) is characterized by a chronically draining middle ear. CSOM is typically treated with multiple courses of antibiotics or antiseptics which are successful in achieving quiescence; however, the disease is prone to relapse. Understanding why these treatment failures occur is essential. STUDY DESIGN: The minimum inhibitory concentration (MIC), minimal biofilm eradication concentration, and the inhibitory zone were determined for ototopicals and ofloxacin for the laboratory strains and CSOM-derived isolates. The percentage of persister cells and bacterial biofilm formation were measured. Disease eradication was tested in a validated in-vivo model of CSOM after treatment with ofloxacin. SETTING: Microbiology Laboratory. METHODS: Basic science experiments were performed to measure the effectiveness of a number of compounds against CSOM bacteria in a number of distinct settings. RESULTS: The minimal biofilm eradication concentration is higher than is physiologically achievable with commercial preparations, except for povo-iodine. Clincial isolates of CSOM have equivalent biofilm-forming ability but increased proportions of persister cells. Ofloxacin can convert to inactive disease temporarily but fails to eradicate disease in an in-vivo model. CONCLUSIONS: Higher percentages of persister cells in clinical CSOM isolates are associated with resistance to ototopicals. Current ototopicals, except povo-iodine, have limited clinical effectiveness; however, it is unknown what the maximum achievable concentration is and there are ototoxicity concerns. Fluoroquinolones, while successful in producing inactive disease in the short term, have the potential to encourage antimicrobial resistance and disease recalcitrance and do not achieve a permanent remission. Given these limitations, clinicians should consider surgery earlier or use of clinically safe concentrations of povo-iodine earlier into the treatment algorithm.

Treatment with a neutrophil elastase inhibitor and ofloxacin reduces P. aeruginosa burden in a mouse model of chronic suppurative otitis media.

Chronic suppurative otitis media (CSOM) is a widespread, debilitating problem with poorly understood immunology. Here, we assess the host response to middle ear infection over the course of a month post-infection in a mouse model of CSOM and in human subjects with the disease. Using multiparameter flow cytometry and a binomial generalized linear machine learning model, we identified Ly6G, a surface marker of mature neutrophils, as the most informative factor of host response driving disease in the CSOM mouse model. Consistent with this, neutrophils were the most abundant cell type in infected mice and Ly6G expression tracked with the course of infection. Moreover, neutrophil-specific immunomodulatory treatment using the neutrophil elastase inhibitor GW 311616A significantly reduces bacterial burden relative to ofloxacin-only treated animals in this model. The levels of dsDNA in middle ear effusion samples are elevated in both humans and mice with CSOM and decreased during treatment, suggesting that dsDNA may serve as a molecular biomarker of treatment response. Together these data strongly implicate neutrophils in the ineffective immune response to P. aeruginosa infection in CSOM and suggest that immunomodulatory strategies may benefit drug-tolerant infections for chronic biofilm-mediated disease.

Chronic otorrhoea, otalgia and hearing loss not responding to antibiotics and tympanoplasty surgery.

Chronic otorrhoea from a tympanic membrane perforation is common. We present the case of a patient who had already received seemingly adequate treatment for his condition in the past. Yet, he presented to our outpatient clinic with worsening otalgia and otorrhoea, progressive hearing loss and a new tympanic membrane perforation. After a thorough otological evaluation, the patient's medical history and the histological specimen from a previous operation were reviewed. The findings met the diagnostic criteria of eosinophilic otitis media. After treatment with topic triamcinolone through the perforated tympanic membrane, the patient's otalgia subsided, hearing levels were improved and the size of the tympanic membrane perforation decreased.

Topical versus systemic antibiotics for chronic suppurative otitis media.

BACKGROUND: Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more than one micro-organism) of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Antibiotics are the most common treatment for CSOM, which act to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be administered both topically and systemically, and can be used alone or in addition to other treatments for CSOM such as ear cleaning (aural toileting). OBJECTIVES: To assess the effects of topical versus systemic antibiotics for people with CSOM. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 March 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least a one-week follow-up involving patients (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks. The studies compared topical antibiotics against systemic (oral, injection) antibiotics. We separated studies according to whether they compared the same type of antibiotic in both treatment groups, or different types of antibiotics. For each comparison we considered whether there was background treatment for both treatment groups, for example aural toileting (ear cleaning). DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not, measured at between one week and up to two weeks, two weeks up to four weeks, and after four weeks), health-related quality of life using a validated instrument, ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways. MAIN RESULTS: Six studies (445 participants), all with high risk of bias, were included. All but two studies included patients with confirmed CSOM, where perforation of the ear drum was clearly documented. None of the studies reported results for resolution of ear discharge after four weeks or health-related quality of life. 1. Topical versus systemic administration of the same type of antibiotics (quinolones) Four studies (325 participants) compared topical versus systemic (oral) administration of ciprofloxacin. Three studies reported resolution of ear discharge at one to two weeks and found that the topical administration may slightly increase resolution (risk ratio (RR) 1.48, 95% confidence interval (CI) 1.24 to 1.76; 285 participants; 3 studies; I2 = 0%; low-certainty evidence). In these studies, aural toileting was either not mentioned, or limited to the first visit. Three studies (265 participants) reported that they did not suspect ototoxicity in any participants, but it is unclear how this was measured (very low-certainty evidence). No studies reported the outcomes of ear pain or serious complications. No studies reported results for hearing, despite it being measured in three studies. 2. Topical versus systemic administration of different types of antibiotics (quinolones versus aminoglycosides) One study (60 participants) compared topical ciprofloxacin versus gentamicin injected intramuscularly. No aural toileting was reported. Resolution of ear discharge was not measured at one to two weeks. The study did not report any 'side effects' from which we assumed that no ear pain, suspected ototoxicity or serious complications occurred (very low-certainty evidence). The study stated that "no worsening of the audiometric function related to local or parenteral therapy was observed". 3. Topical versus systemic administration of different types of antibiotics (quinolones versus amoxicillin-clavulanic acid) One study compared topical ofloxacin with amoxicillin-clavulanic acid with all participants receiving suction ear cleaning at the first visit. It is uncertain if there is a difference between the two groups in resolution of ear discharge at one to two weeks due to study limitations and the very small sample size (RR 2.93, 95% CI 1.50 to 5.72; 56 participants; very low-certainty evidence). It is unclear if there is a difference between topical quinolone compared with oral amoxicillin-clavulanic acid with regards to ear pain, hearing or suspected ototoxicity (very low-certainty evidence). No studies reported the outcome of serious complications. AUTHORS' CONCLUSIONS: There was a limited amount of low-quality evidence available, from studies completed over 15 years ago, to examine whether topical or systemic antibiotics are more effective in achieving resolution of ear discharge for people with CSOM. However, amongst this uncertainty there is some evidence to suggest that the topical administration of antibiotics may be more effective than systemic administration of antibiotics in achieving resolution of ear discharge (dry ear). There is limited evidence available regarding different types of antibiotics. It is not possible to determine with any certainty whether or not topical quinolones are better or worse than systemic aminoglycosides. These two groups of compounds have different adverse effect profiles, but there is insufficient evidence from the included studies to make any comment about these. In general, adverse effects were poorly reported.

Bacteriological Profile of Chronic Suppurative Otitis Media and Antibiotic Susceptibility in a Tertiary Care Hospital in Shanghai, China.

OBJECTIVE: Chronic suppurative otitis media (CSOM) is mostly caused by bacterial infection of the middle ear and antibiotics are generally used empirically, which may lead to the emergence of resistant bacterial strains. The objective of the study is to assess the bacteriological profile of and evaluate the antibiotic susceptibility of strains isolated in a tertiary care hospital in Shanghai, China. METHODS: This study included 289 individuals with clinical diagnosis of CSOM. Middle ear purulent discharge was obtained with sterile swabs and cultured for bacterial pathogens. The susceptibility of the isolated microorganisms to antibiotics was assessed by a microdilution method. RESULTS: Bacterial pathogens were found in 223 (77.2%) of the 289 cases. A total of 236 strains were isolated. Staphylococcus aureus was the commonest bacteria (44.9%) followed by Pseudomonas aeruginosa (16.9%) and coagulase-negative Staphylococcus (8.5%). There were 18.9% methicillin-resistant S aureus (MRSA) among the obtained S aureus organisms. Multidrug-resistant P aeruginosa was found in 4 patients, making up 10% of all detected P aeruginosa. Staphylococcus aureus showed highest susceptibility to vancomycin (100%), then gentamicin (98.1%) and rifampicin (97.2%) and was most resistant to penicillin (61.3%) and erythromycin (50%). All isolated P aeruginosa showed susceptibility to piperacillin, piperacillin/tazobactam, and meropenem. High degree of resistance in P aeruginosa was observed toward levofloxacin (42.5%), ciprofloxacin (40%), and ceftriaxone (30%). CONCLUSION: The high prevalence of MRSA and fluoroquinolone-resistant P aeruginosa indicated cephalosporins and fluoroquinolone as primary empirical antibiotic drugs in CSOM to be cautiously used. In order to reduce the incidence of resistant strains and promote effective usage of antibiotics, all aural discharges should be cultured to determine antibacterial susceptibility patterns before treatment.

A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation.

Chronic suppurative otitis media (CSOM) is a neglected pediatric disease affecting 330 million worldwide for which no new drugs have been introduced for over a decade. We developed a mouse model with utility in preclinical drug evaluation and antimicrobial discovery. Our model used immune-competent mice, tympanic membrane perforation and inoculation with luminescent Pseudomonas aeruginosa that enabled bacterial abundance tracking in real-time for 100 days. The resulting chronic infection exhibited hallmark features of clinical CSOM, including inhibition of tympanic membrane healing and purulent ear discharge. We evaluated the standard care fluoroquinolone ofloxacin and demonstrated that this therapy resulted in a temporary reduction of bacterial burden. These data are consistent with the clinical problem of persistent infection in CSOM and the need for therapeutic outcome measures that assess eradication post-therapeutic endpoint. We conclude that this novel mouse model of CSOM has value in investigating new potential therapies.