How common is otogenic meningitis? A retrospective study in southern Sweden over 18 years.

BACKGROUND: Bacterial meningitis is a rare, but life-threatening disease, which sometimes occurs as a complication to acute otitis media (AOM). The proportion of meningitis cases originating from AOM is not clear. PURPOSE: The aim of this study was to investigate the proportion of meningitis cases caused by AOM, to compare risk factors, bacteriology and outcome between otogenic and non-otogenic meningitis, and to analyse the incidence of bacterial meningitis after the introduction of conjugate pneumococcal vaccines (PCV). METHODS: The medical charts of all patients admitted to hospitals in southern Sweden with bacterial meningitis between 2000 and 2017 were retrieved. Based on otoscopy and/or imaging, the proportion of otogenic meningitis cases was calculated, as were annual incidences. RESULTS: A total of 216 patients were identified, 25 of whom died. The proportion of otogenic meningitis was 31% but varied from 6% among teenagers to 40% among adults. Before PCV, 23% of all meningitis cases were children < 2 years, compared to 1% post-PCV. The average incidence in the adult population, on the other hand, increased post-PCV, though there were large annual variations. S. pneumoniae was the most commonly identified pathogen in everyone but teenagers, in whom N. meningitidis was predominant. CONCLUSION: AOM is an important cause of meningitis in children and adults. Though bacterial meningitis almost disappeared in children < 2 years after the introduction of PCV, the incidence of pneumococcal meningitis in adults seems to have increased.

Hearing loss after bacterial meningitis, a retrospective study.

BACKGROUND: Hearing loss is a common sequela after bacterial meningitis, but risk factors for this are poorly studied, particularly in relation to concurrent acute otitis media (AOM). AIMS: The aim of this study was to investigate incidence and risk factors for hearing loss in patients treated for bacterial meningitis. METHODS: In this retrospective study, medical records for patients admitted to hospital with bacterial meningitis in Skåne county, Sweden, between 2000 and 2017 were retrieved. The association between risk factors and hearing loss was estimated using logistic regression. RESULTS: During the 18 years, 187 cases of meningitis were identified. Hearing loss was confirmed in 71 of the 119 patients who had done an audiometry. It was significantly more common in adults. There was also evidence of an association between hearing loss and AOM, and between hearing loss and pneumococcal infection. CONCLUSION: Age, concurrent AOM and pneumococcal infection were risk factors for developing hearing loss. Despite being recommended in the national guidelines, more than a third of the patients had not done a hearing test after recovering from bacterial meningitis. The findings strengthen the demand for prompt ear examination and - if needed - tympanocentesis in meningitis patients.

Pneumococcal vaccination in children at risk of developing recurrent acute otitis media - a randomized study.

AIM: Acute otitis media (AOM) is a common childhood disease, which often becomes recurrent (rAOM). A small reduction in AOM episodes has been noted in unselected child cohorts after vaccination with heptavalent conjugate pneumococcal vaccine (PCV7). The purpose of this study was to investigate how vaccination affects young children at risk of developing rAOM. METHODS: Ninety-six children with an AOM onset before 6 months of age, implying a high risk for rAOM, were closely monitored until the age of 2 years. Forty-six were vaccinated with PCV7 and 50 were not. All episodes of AOM, emergency visits and ventilation tube insertions were registered. RESULTS: A total of 363 AOM episodes were diagnosed. The incidence was reduced by 26% (p = 0.03), the number of emergency visits because of suspected AOM by 36% (p = 0.01) and the proportion of children who received ventilation tubes was halved in the vaccine group (p = 0.02). CONCLUSIONS: During the first 2 years of life, PCV7 significantly reduced AOM episodes, emergency visits and ventilation tube insertions in children with rAOM. Pneumococcal vaccine may be a future route to reduce antibiotic use and health care consumption in otitis-prone children.

Nasopharyngeal cultures in children with AOM - A retrospective study on bacteriological findings and impact on management.

BACKGROUND: Despite a far from perfect correlation with middle ear growth, nasopharyngeal cultures are sometimes used in children with acute otitis media (AOM) in order to have some idea of the causative pathogen. How these cultures are used in clinical practice and to what extent they influence clinical management has not previously been studied. The objective with this study was to investigate in what circumstances nasopharyngeal cultures are performed in children with AOM, what the bacteriological results are and to what extent cultures influence clinical management. METHODS: All nasopharyngeal cultures taken in clinical practice from children with AOM in the county of Skåne, Sweden, during 2017-2018 were retrieved together with details from the medical charts two months prior to and one month after the culture. Information about the reason for culturing, the bacteriological result, and whether this result changed the management of the child, was retrieved from the charts. RESULTS: During the 2 years, 978 nasopharyngeal cultures were taken in children with AOM. The most common reasons for obtaining a culture was a recurrence of AOM (40%) or treatment failure (22%). Many of the children had ongoing or recent antibiotic treatment. M. catarrhalis was the most commonly identified pathogen (53%), followed by H. influenzae (30%) and S. pneumoniae (14%). Resistance rates were low, and the most commonly identified resistant pathogen was betalactamase-negative ampicillin-resistant H. influenzae. One in five cultures led to a change in management, such as a change of antibiotics or an additional check-up. This was most commonly seen in association with H. influenzae, reflecting clinical practice in Sweden, where AOM is primarily treated with penicillin V. CONCLUSION: Despite not having a perfect correlation with middle ear growth, nasopharyngeal cultures can provide clues about suitable alternative antibiotics in cases of treatment failure, and they can help monitoring nasopharyngeal carriage and resistance rates.

Acute mastoiditis in southern Sweden: a study of occurrence and clinical course of acute mastoiditis before and after introduction of new treatment recommendations for AOM.

Watchful waiting was recommended as an option for uncomplicated episodes of acute otitis media in Sweden in the year 2000. Concern was raised that these recommendations would lead to a higher incidence of acute mastoiditis. The aim of this study was to map the occurrence, treatment policy and the clinical course of mastoiditis before and after the new treatment recommendations were introduced. Included in the study were all patients (adults and children) who were admitted to two ENT departments in southern Sweden for acute mastoiditis from 1996 to 2005. A total of 42 cases of mastoiditis were identified: 23 during the first period of 1996-2000 and 19 during 2001-2005. Mastoidectomy was performed in 14 patients during the first period and in 8 during the second period. As much as 39% of mastoiditis patients received antibiotics before hospital care, but had no improvement. There was no indication that the number of patients with acute mastoiditis was increasing after new treatment recommendation of AOM. There was no increase in the occurrence of mastoidectomy. Severe complications of mastoiditis were rare. Although there were potentially threatening complications of mastoiditis in the study, these did not lead to sequelae. It is important to follow up the consequences when treatment recommendations of AOM are changed.

Nasopharyngeal cultures in children; when, what and why?

INTRODUCTION: Nasopharyngeal cultures are commonly used to determine the causative bacteria in upper airway infections. However, several bacteria can occupy the nasopharynx simultaneously and most healthy children are asymptomatic carriers of presumptive pathogens. This makes the interpretation of nasopharyngeal cultures difficult. Knowledge about which bacteria reside in the nasopharynx can assist the physician in the choice of antibiotic treatment and might also predict the risk of complications. Today, little is known about how nasopharyngeal cultures are being used in clinical practice. OBJECTIVES: The aim of this study was to explore how nasopharyngeal cultures are used in clinical practice, when and why they are performed, what they show, and what impact they have on the treatment of the patient. METHODS: The results of all nasopharyngeal cultures taken from children aged 0-12 years in the county of Skåne, Sweden, during 2018 were obtained. Medical charts from hospitals and primary care centres were used to determine why the cultures were taken and whether they resulted in a change of treatment. RESULTS: During 2018, 2200 nasopharyngeal cultures were taken, most of them during the winter season. Forty-one percent of children had on-going antibiotic treatment or had been treated with antibiotics in the previous two months. Acute otitis media (AOM) was the most common reason for taking a culture. The most frequently identified bacteria were Moraxella catarrhalis and Haemophilus influenzae. There was a positive correlation between M. catarrhalis on one hand and Streptococcus pneumoniae and H. influenzae on the other. Overall, bacterial resistance was rare. The presence of beta-lactamase negative ampicillin resistant H. influenzae was associated with recent or on-going antibiotics, whereas S. pneumoniae with decreased penicillin susceptibility were found less frequently in the same group of children. A positive culture resulted in a change of treatment in 29% of the cases. CONCLUSION: Apart from playing a confirmatory role and monitoring the incidence of resistant bacteria, almost a third of the nasopharyngeal cultures analysed in this study contributed to decision-making. It therefore appears that bacterial sampling have a role in clinical practice. It would be valuable to study more closely why nasopharyngeal cultures are taken in during AOM and how the result affects the treatment.

Panel 2- recent advance in otitis media bioinformatics.

OBJECTIVES: To update the medical literature on recent large-scale studies employing bioinformatics data analysis tools in otitis media (OM) disease models with a principal focus on developments in the past 5 years. DATA SOURCES: Pubmed indexed peer-reviewed articles. REVIEW METHODS: Comprehensive review of the literature using the following search terms: 'genomics, inflammasome, microRNA, proteomics, transcriptome, bioinformatics' with the term 'otitis media', and 'middle ear'. Included articles published in the English language from January 1, 2015-April 1, 2019. IMPLICATIONS FOR PRACTICE: Large scale bioinformatics tools over the past five years lend credence to the paradigm of innate immune response playing a critical role in host defense against bacteria contributing to Otitis Media (OM) progression from acute to chronic. In total, genomic, miRNAomic, and proteomic analyses all point to the need for a tightly regulated innate immune and inflammatory response in the middle ear. Currently, there is an urgent need for developing novel therapeutic strategies to control immunopathology and tissue damage, improve hearing and enhance host defense for both acute and chronic OM based on full understanding of the basic molecular pathogenesis of OM.

Panel 1: Biotechnology, biomedical engineering and new models of otitis media.

OBJECTIVE: To summarize recently published key articles on the topics of biomedical engineering, biotechnology and new models in relation to otitis media (OM). DATA SOURCES: Electronic databases: PubMed, Ovid Medline, Cochrane Library and Clinical Evidence (BMJ Publishing). REVIEW METHODS: Articles on biomedical engineering, biotechnology, material science, mechanical and animal models in OM published between May 2015 and May 2019 were identified and subjected to review. A total of 132 articles were ultimately included. RESULTS: New imaging technologies for the tympanic membrane (TM) and the middle ear cavity are being developed to assess TM thickness, identify biofilms and differentiate types of middle ear effusions. Artificial intelligence (AI) has been applied to train software programs to diagnose OM with a high degree of certainty. Genetically modified mice models for OM have further investigated what predisposes some individuals to OM and consequent hearing loss. New vaccine candidates protecting against major otopathogens are being explored and developed, especially combined vaccines, targeting more than one pathogen. Transcutaneous vaccination against non-typeable Haemophilus influenzae has been successfully tried in a chinchilla model. In terms of treatment, novel technologies for trans-tympanic drug delivery are entering the clinical domain. Various growth factors and grafting materials aimed at improving healing of TM perforations show promising results in animal models. CONCLUSION: New technologies and AI applications to improve the diagnosis of OM have shown promise in pre-clinical models and are gradually entering the clinical domain. So are novel vaccines and drug delivery approaches that may allow local treatment of OM. IMPLICATIONS FOR PRACTICE: New diagnostic methods, potential vaccine candidates and the novel trans-tympanic drug delivery show promising results, but are not yet adapted to clinical use.

International registry of otolaryngologist-head and neck surgeons with COVID-19.

BACKGROUND: It has become clear that healthcare workers are at high risk, and otolaryngology has been theorized to be among the highest risk specialties for coronavirus disease 2019 (COVID-19). The purpose of this study was to detail the international impact of COVID-19 among otolaryngologists, and to identify instructional cases. METHODS: Country representatives of the Young Otolaryngologists-International Federation of Otolaryngologic Societies (YO-IFOS) surveyed otolaryngologists through various channels. Nationwide surveys were distributed in 19 countries. The gray literature and social media channels were searched to identify reported deaths of otolaryngologists from COVID-19. RESULTS: A total of 361 otolaryngologists were identified to have had COVID-19, and data for 325 surgeons was available for analysis. The age range was 25 to 84 years, with one-half under the age of 44 years. There were 24 deaths in the study period, with 83% over age 55 years. Source of infection was likely clinical activity in 175 (54%) cases. Prolonged exposure to a colleague was the source for 37 (11%) surgeons. Six instructional cases were identified where infections occurred during the performance of aerosol-generating operations (tracheostomy, mastoidectomy, epistaxis control, dacryocystorhinostomy, and translabyrinthine resection). In 3 of these cases, multiple operating room attendees were infected, and in 2, the surgeon succumbed to complications of COVID-19. CONCLUSION: The etiology of reported cases within the otolaryngology community appear to stem equally from clinical activity and community spread. Multiple procedures performed by otolaryngologists are aerosol-generating procedures (AGPs) and great care should be taken to protect the surgical team before, during, and after these operations.

Tympanic membrane changes in experimental acute otitis media and myringotomy.

OBJECTIVE: The present experimental study explored pathomorphological changes and calcium depositions in the tympanic membrane during experimental acute otitis media caused by nontypeable Haemophilus influenzae in myringotomized and nonmyringotomized ears. MATERIAL AND METHODS: A rat model of experimental acute otitis media caused by nontypeable Haemophilus influenzae was employed. Sixteen Sprague-Dawley rats were used. Four days following middle ear inoculation, a bilateral myringotomy was performed in six randomly selected animals. Another group of 10 animals was inoculated only. On days 4, 7, 14, and 28 after inoculation, two animals from each group were sacrificed. The temporal bones were removed and the tympanic membranes were dissected, followed by paraffin embedding. Adjacent sections were stained with PAS-alcian blue for basic histopathological observations and by von Kossa method for determination of calcium phosphate depositions. RESULTS: Particularly intense invasion of polymorphonuclear neutrophil leukocytes was seen on day 4 after inoculation. The highest infiltration of macrophages was observed on day 7. The peak number of lymphocytes was seen on day 14. No difference occurred in the number of polymorphonuclear leukocytes in myringotomized and nonmyringotomized tympanic membranes. The infiltration with lymphocytes and activated macrophages in all parts of the myringotomized tympanic membranes was statistically significantly higher than in the nonmyringotomized animals. The total amount of interstitial calcium phosphate depositions during days 7, 14, and 28 of study was statistically higher in the sections of pars tensa from myringotomized membranes compared to the nonmyringotomized membranes. CONCLUSION: Nontypeable Haemophilus influenzae-induced acute otitis media and myringotomy provoke more extensive inflammatory reaction with microcalcification in the tympanic membranes.

Prediction of upper respiratory tract bacteria in acute otitis media.

CONCLUSIONS: Thorough otomicroscopical examination of the tympanic membrane in acute otitis media (AOM) might distinguish AOM episodes caused by different bacteria. It thus might be a way to select appropriate treatment for each patient without raising the number of dangerous complications. OBJECTIVES: The aim of this study was to see if it might be possible to predict the causative bacterium by judging the otomicroscopical appearance of the tympanic membrane in episodes of AOM. PATIENTS AND METHODS: The study was prospective. Patients suffering from non-perforated AOM were included. The tympanic membrane was photographed. A prediction of the causative bacterium was made and tympanocentesis was performed. Effusion from the middle ear and a nasopharyngeal swab were obtained for bacterial culturing. The causative bacteria were categorized into gram-positive (Streptococcus pneumoniae and S. pyogenes) or gram-negative (non-typable Haemophilus influenzae and Moraxella catarrhalis). RESULTS: A total of 82 patients were included in the study. A correct prediction was made in 47/63, a false prediction in 16/63 (kappa 0.48, p<0.001).

Panel 8: Report on Recent Advances in Molecular and Cellular Biochemistry.

Objectives To update the medical literature on recent cellular and molecular advances in otitis media disease models with a principal focus on developments in the past 5 years. We also aim to explain recent translational advances in cellular and molecular biology that have influenced our understanding and management of otitis media. Data Sources PubMed-indexed peer-reviewed articles. Review Methods A comprehensive review of the literature was conducted with the term otitis media and the following search terms: molecular biology, cell biology, innate immunity, oxidative stress, mucins, molecular diagnostics. Included articles were published in the English language from January 1, 2010, to July 31, 2015. Implications for Practice The molecular understanding of otitis media disease progression has rapidly advanced over the last 5 years. The roles of inflammation, mucins, and cell signaling mechanisms have been elucidated and defined. Advances in the field provide a plethora of opportunities for innovative molecular targeting in the development of novel therapeutic strategies for otitis media.

Otomicroscopic findings and systemic interleukin-6 levels in relation to etiologic agent during experimental acute otitis media.

The aim of the present study was to explore whether it was possible to differentiate the clinical course and the otomicroscopic appearance of acute otitis media (AOM) caused by common otitis pathogens in an animal model. Systemic interleukin (IL)-6 levels as early markers for bacterial AOM were also studied. Four groups of rats were inoculated with either Streptococcus pneumoniae, Streptococcus pyogenes, non-typeable Haemophilus influenzae or Moraxella catarrhalis. The animals were monitored by otomicroscopy, photos of the tympanic membrane, cultures and IL-6 detection in serum the following 4 days. The gram-positive S. pneumoniae and S. pyogenes induced severe AOM with opaque effusion behind the tympanic membrane, pronounced dilation of the vessels and spontaneous perforations. The gram-negative H. influenzae and M. catarrhalis induced a less severe infection with cloudy, sometimes foamy effusion, and no spontaneous perforations. With the otomicroscopic findings it was possible to distinguish between infections induced by gram-positive bacteria and gram-negative bacteria. Detection of interleukin-6 in serum appeared to be of limited use for all infections except the pneumococcal AOM, but this needs to be further investigated.

Calcium deposition and expression of bone modelling markers in the tympanic membrane following acute otitis media.

BACKGROUND AND OBJECTIVES: In accordance with clinical findings, myringosclerosis develops after otitis media (OM) and paracentesis in an experimental setting. The pathogenesis of this phenomenon of calcification is poorly understood. As the calcification process and the sclerotic plaques of the drum mimics features of bone tissue, this study explores tympanic membrane calcium deposition in association with the expression of three bone modelling markers: osteopontin (OPN), osteoprotegerin (OPG) and osteonectin (ON). OPN is secreted by osteoblasts and is found at calcification sites, e.g. during pathological calcification in chronic OM. The cytokine OPG is an inhibitor of bone resorption and consequently bone remodelling. ON is a calcium binding glycoprotein necessary for the maintenance of bone mass and remodelling. It is found in bone matrix and synthesized by osteoblasts. METHOD: A rat model of acute otitis media (AOM) caused by non-typeable Haemophilus influenzae was used. Four days following middle ear inoculation, a myringotomy was performed in six animals. Another group of ten animals was inoculated only. The drum was dissected in two animals from each group on day 4, 7, 14 and 28 post-inoculation, and the expression of OPN, OPG and ON was determined by immunohistochemistry. von Kossa staining determined the deposition of calcium and immune staining for CD68 identified macrophages. RESULTS: Calcium depositions were initially accumulated in the cytoplasm of macrophages and dispersed in the connective tissue layers of the pars flaccida and tensa. Late accumulation occurred in the lamina propria of pars tensa, more extensively in myringotomized ears. OPN expression was found early in inflammatory cells including especially macrophages and late in pars tensa fibrocytes. OPG expression was initially located to inflammatory cells and late to pars tensa fibrocytes and the inner basal membrane of pars flaccida. Some ears displayed a marked pars flaccida expression of ON in the connective tissue matrix on early days and at the inner basal membrane on later days. The latter cases were from myringotomized ears. Otherwise, no apparent differences of marker expression occurred between myringotomized and non-myringotomized animals. CONCLUSION: We conclude that osteopontin, osteoprotegerin and osteonectin are expressed by different cell types in the tympanic membrane during calcification in association with AOM, with or without myringotomy. These molecules may accordingly play a role in the pathogenesis of myringosclerosis, in which macrophages and fibrocytes appear as potential major players.

Individual-level effects of antibiotics on colonizing otitis pathogens in the nasopharynx.

BACKGROUND: Although there is evidence of an association between antibiotic consumption and resistant bacteria on a population level, the relationship on an individual level has been less well studied, particularly in terms of nasopharyngeal colonization. We have therefore analysed this association, using data from a closely followed cohort of children taking part in a vaccination trial. METHODS: 109 children with early onset of acute otitis media (AOM) were randomised to heptavalent pneumococcal conjugate vaccine (PCV7) or no vaccination. They were followed for three years with scheduled appointments as well as sick visits. Nasopharyngeal cultures were obtained at all visits. Antibiotic treatments were recorded, as were risk factors for AOM, including siblings, short breast-feeding and parental smoking. Data were entered into a Cox regression model, and the findings of Streptococcus pneumoniae and Haemophilus influenzae with reduced susceptibility to the penicillin group were related to the number of previous courses of antibiotics. RESULTS: There was evidence of an association between the amount of previously consumed betalactams and colonization with beta-lactamasenegative ampicillin-resistant (BLNAR) H. influenzae (RR 1.21; 95% CI 1.03-1.43; p = 0.03), and also with the most commonly prescribed drug; amoxicillin (RR 1.39; 95% CI 1.09-1.76; p = 0.01). There was no evidence for an association between antibiotic consumption and betalactamase producing H. influenzae or S. pneumoniae with reduced susceptibility to penicillin. Furthermore, there was no evidence of an association between resistant bacteria and AOM risk factors or PCV7. CONCLUSION: In this subgroup of children, most of whom were given several courses of antibiotics in early childhood, there was evidence of an association between betalactam/amoxicillin consumption and nasopharyngeal colonization with BLNAR strains, bacteria that have increased in prevalence during the last 10-15 years, and that are notoriously difficult to treat with oral antibiotics.

Development of myringosclerosis during acute otitis media caused by Streptococcus pneumoniae and non-typeable Haemophilus influenzae: a clinical otomicroscopical study using the rat model.

OBJECTIVE: The present study was performed in order to study development of myringosclerosis during acute otitis media caused by different bacteria in myringotomized and non-myringotomized ears. MATERIAL AND METHODS: A rat model of acute otitis media caused by Streptococcus pneumoniae type 3 and non-typeable Haemophilus influenzae was used. A sample consisted of 42 animals. Four days following middle ear inoculation, a myringotomy was performed in 10 animals from the Streptococcus pneumoniae group and 6 from the non-typeable Haemophilus influenzae group. Another group of 24 animals was inoculated only. On day 4, 7, 14 and 28 after inoculation the status of the drum was inspected under the otomicroscope for vascular reaction, effusion, perforation, myringosclerosis and scarring. RESULTS: On day 4 after inoculation all infected ears had typical signs of acute otitis media. Tympanic membranes healed with scar formation in most cases of myringotomized Streptococcus pneumoniae type 3 infection and deposition of sclerotic plaques was observed by day 14. Otomicroscopically visible myringosclerosis was not found after non-typeable Haemophilus influenzae induced acute otitis media neither in myringotomized nor in non-myringotomized animals. We conclude that Streptococcus pneumoniae type 3 provokes a severe clinical course of acute otitis media that healed with scarring and myringosclerosis formation in the tympanic membrane. Clinically visible myringosclerosis develops after middle ear infection caused by Streptococcus pneumoniae type 3, but not in cases caused by non-typeable Haemophilus influenzae.

Effect of pneumococcal conjugate vaccination on nasopharyngeal carriage in children with early onset of acute otitis media - a randomized controlled trial.

CONCLUSION: Although children vaccinated with heptavalent pneumococcal conjugate vaccine (PCV) had fewer episodes of acute otitis media (AOM), this trial was unable to prove a simultaneous decrease in nasopharyngeal carriage. OBJECTIVE: Carriage rates of AOM pathogens in the nasopharynx are high among children, and colonization is the first step towards infection. The possible impact of PCV on carriage is therefore of interest, particularly in children with recurrent AOM. The aims of this study were to examine the effect of heptavalent PCV on carriage of AOM pathogens in children at high risk of developing recurrent disease, and to monitor carriage of resistant pathogens in vaccinated and unvaccinated children. METHODS: A total of 109 children with an onset of AOM before 6 months of age, 89 of whom developed recurrent disease, were enrolled in a trial. Fifty-two children were vaccinated and all were closely monitored for 3 years. RESULTS: There was no difference statistically between vaccinated children and controls concerning the carriage of any of the major AOM pathogens. There was evidence of within-child clustering for S. pneumoniae (p = 0.002) and H. influenzae (p < 0.001), indicating that children continued to carry either species over time. Resistance rates were generally low and comparable with national levels.