Infant microbes and metabolites point to childhood neurodevelopmental disorders.

This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.

Nasal Delivery of Haemophilus haemolyticus Is Safe, Reduces Influenza Severity, and Prevents Development of Otitis Media in Mice.

BACKGROUND: Despite vaccination, influenza and otitis media (OM) remain leading causes of illness. We previously found that the human respiratory commensal Haemophilus haemolyticus prevents bacterial infection in vitro and that the related murine commensal Muribacter muris delays OM development in mice. The observation that M muris pretreatment reduced lung influenza titer and inflammation suggests that these bacteria could be exploited for protection against influenza/OM. METHODS: Safety and efficacy of intranasal H haemolyticus at 5 × 107 colony-forming units (CFU) was tested in female BALB/cARC mice using an influenza model and influenza-driven nontypeable Haemophilus influenzae (NTHi) OM model. Weight, symptoms, viral/bacterial levels, and immune responses were measured. RESULTS: Intranasal delivery of H haemolyticus was safe and reduced severity of influenza, with quicker recovery, reduced inflammation, and lower lung influenza virus titers (up to 8-fold decrease vs placebo; P ≤ .01). Haemophilus haemolyticus reduced NTHi colonization density (day 5 median NTHi CFU/mL = 1.79 × 103 in treatment group vs 4.04 × 104 in placebo, P = .041; day 7 median NTHi CFU/mL = 28.18 vs 1.03 × 104; P = .028) and prevented OM (17% OM in treatment group, 83% in placebo group; P = .015). CONCLUSIONS: Haemophilus haemolyticus has potential as a live biotherapeutic for prevention or early treatment of influenza and influenza-driven NTHi OM. Additional studies will deem whether these findings translate to humans and other respiratory infections.

Auditory Deprivation during Development Alters Efferent Neural Feedback and Perception.

Auditory experience plays a critical role in hearing development. Developmental auditory deprivation because of otitis media, a common childhood disease, produces long-standing changes in the central auditory system, even after the middle ear pathology is resolved. The effects of sound deprivation because of otitis media have been mostly studied in the ascending auditory system but remain to be examined in the descending pathway that runs from the auditory cortex to the cochlea via the brainstem. Alterations in the efferent neural system could be important because the descending olivocochlear pathway influences the neural representation of transient sounds in noise in the afferent auditory system and is thought to be involved in auditory learning. Here, we show that the inhibitory strength of the medial olivocochlear efferents is weaker in children with a documented history of otitis media relative to controls; both boys and girls were included in the study. In addition, children with otitis media history required a higher signal-to-noise ratio on a sentence-in-noise recognition task than controls to achieve the same criterion performance level. Poorer speech-in-noise recognition, a hallmark of impaired central auditory processing, was related to efferent inhibition, and could not be attributed to the middle ear or cochlear mechanics.SIGNIFICANCE STATEMENT Otitis media is the second most common reason children go to the doctor. Previously, degraded auditory experience because of otitis media has been associated with reorganized ascending neural pathways, even after middle ear pathology resolved. Here, we show that altered afferent auditory input because of otitis media during childhood is also associated with long-lasting reduced descending neural pathway function and poorer speech-in-noise recognition. These novel, efferent findings may be important for the detection and treatment of childhood otitis media.

An infant mouse model of influenza-driven nontypeable Haemophilus influenzae colonization and acute otitis media suitable for preclinical testing of novel therapies.

Nontypeable Haemophilus influenzae (NTHi) is a major otitis media (OM) pathogen, with colonization a prerequisite for disease development. Most acute OM is in children <5 years old, with recurrent and chronic OM impacting hearing and learning. Therapies to prevent NTHi colonization and/or disease are needed, especially for young children. Respiratory viruses are implicated in driving the development of bacterial OM in children. We have developed an infant mouse model of influenza-driven NTHi OM, as a preclinical tool for the evaluation of safety and efficacy of clinical therapies to prevent NTHi colonization and the development of OM. In this model, 100% of infant BALB/cARC mice were colonized with NTHi, and all developed NTHi OM. Influenza A virus (IAV) facilitated the establishment of dense (1 × 105 CFU/mL) and long-lasting (6 days) NTHi colonization. IAV was essential for the development of NTHi OM, with 100% of mice in the IAV/NTHi group developing NTHi OM compared with 8% of mice in the NTHi only group. Histological analysis and cytokine measurements revealed that the inflammation observed in the middle ear of the infant mice with OM reflected inflammation observed in children with OM. We have developed the first infant mouse model of NTHi colonization and OM. This ascension model uses influenza-driven establishment of OM and reflects the clinical pathology of bacterial OM developing after a respiratory virus infection. This model provides a valuable tool for testing therapies to prevent or treat NTHi colonization and disease in young children.

Otitis in Patients With Community-Acquired Bacterial Meningitis: A Nationwide Prospective Cohort Study.

BACKGROUND: Otitis is commonly associated with community-acquired bacterial meningitis, but the role of ear surgery as treatment is debated. In this study, we investigated the impact of otitis and ear surgery on outcome of adults with community-acquired bacterial meningitis. METHODS: We analyzed episodes of adults with community-acquired bacterial meningitis from a nationwide prospective cohort study in the Netherlands, between March 2006 and July 2021. RESULTS: A total of 2548 episodes of community-acquired bacterial meningitis were evaluated. Otitis was present in 696 episodes (27%). In these patients the primary causative pathogen was Streptococcus pneumoniae (615 of 696 [88%]), followed by Streptococcus pyogenes (5%) and Haemophilus influenzae (4%). In 519 of 632 otitis episodes (82%) an ear-nose-throat specialist was consulted, and surgery was performed in 287 of 519 (55%). The types of surgery performed were myringotomy with ventilation tube insertion in 110 of 287 episodes (38%), mastoidectomy in 103 of 287 (36%), and myringotomy alone in 74 of 287 (26%). Unfavorable outcome occurred in 210 of 696 episodes (30%) and in 65 of 696 episodes was fatal (9%). Otitis was associated with a favorable outcome in a multivariable analysis (odds ratio 0.74; 95% confidence interval [CI] .59-.92; P = .008). There was no association between outcome and ear surgery. CONCLUSIONS: Otitis is a common focus of infection in community-acquired bacterial meningitis in adults, with S. pneumoniae being the most common causative pathogen. Presence of otitis is associated with a favorable outcome. Ear surgery's impact on the outcome of otogenic meningitis patients remains uncertain.

Auritidibacter ignavus, an Emerging Pathogen Associated with Chronic Ear Infections.

We describe detection of the previously rarely reported gram-positive bacterium Auritidibacter ignavus in 3 cases of chronic ear infections in Germany. In all 3 cases, the patients had refractory otorrhea. Although their additional symptoms varied, all patients had an ear canal stenosis and A. ignavus detected in microbiologic swab specimens. A correct identification of A. ignavus in the clinical microbiology laboratory is hampered by the inability to identify it by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Also, the bacterium might easily be overlooked because of its morphologic similarity to bacterial species of the resident skin flora. We conclude that a high index of suspicion is warranted to identify A. ignavus and that it should be particularly considered in patients with chronic external otitis who do not respond clinically to quinolone ear drop therapy.

Microbiological study of the auditory canal in dairy calves with otitis media.

Otitis media (OM) in calves, is caused by different bacteria. OM treatment requires identification of etiological agents and antibiotic sensitivity testing. The gold standard method of bacteriological study of OM is tympanocentesis, but using this technique in farm condition would be difficult. As a hypothesis, it is possible that bacteriologic examining the auditory canal can help to accelerate the bacteriological investigation of OM. This study was conducted with the aim of comparing the microbiota of the auditory canal in healthy calves and calves with OM. The present research which was a case-control study, mainly compared control group (18 swab samples from healthy and non-infected ear) with two case groups (20 swab samples from the non-affected ear and 32 swab samples from the affected ear in unilateral OM, 11 swab samples from both affected ears in bilateral OM). The results of bacteriological investigations showed three categories of bacteria including: pathogens (Staphylococcus chromogenes, Corynebacterium pilosum, Corynebacterium ovis, Pseudomonas aeruginosa, Pasteurella multocida, Proteus vulgaris, Trueperella pyogenes, Klebsiella, Escherichia coli, Mycoplasma bovis), opportunists (Staphylococcus intermedius, Bacillus licheniformis) and commensals (Staphylococcus epidermidis, Corynebacterium bovis, Corynebacterium renale, Bacillus subtilis, Bacillus cereus). Based on the antibiotic sensitivity test of the isolates, enrofloxacin, florfenicol, and gentamicin were the chosen antibiotics for treatment. All affected animals were treated based on bacteriological results and antibiotic sensitivity tests. All treated animals were fully cured. Based on the results, it seems that in calves with OM, examining the microbiota of the auditory canal can be further studied as an alternative to tympanocentesis in farm conditions.

Neutrophil Extracellular Trap Formation and Deoxyribonuclease I Activity in Patients with Otitis Media with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

INTRODUCTION: No previous studies have evaluated the levels of neutrophil extracellular trap (NET) remnants or the importance of deoxyribonuclease (DNase) I activity based on the disease activity of otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV). The aim of this study was to explore the formation of NETs in the middle ear of patients with OMAAV during the onset and remission phases of the disease, with a particular focus on the relationships between the quantifiable levels of NET remnants and DNase I activity. METHODS: OMAAV patients were eligible for inclusion. Patients with otitis media with effusion (OME) were examined as controls. The levels of cell-free deoxyribonucleic acid (DNA), citrullinated-histone H3 (cit-H3)-DNA complex, and myeloperoxidase (MPO)-DNA complex were quantified using an enzyme-linked immunosorbent assay. DNase I activity was measured using a fluorometric method. RESULTS: The quantifiable levels of cell-free DNA, cit-H3-DNA complex, and MPO-DNA complex in the middle ear lavage of patients with OMAAV at onset were significantly higher than those in patients with OMAAV at remission and in patients with OME. DNase I activity in the patients with OMAAV at onset was significantly lower than those in patients with OMAAV at remission and OME and was negatively correlated with the level of MPO-DNA complex. CONCLUSIONS: This study suggests that NET remnants and DNase I activity may be potentially useful biomarkers for the diagnosis and disease activity of OMAAV.

Group A Streptococcal meningitis in children: a short case series and systematic review.

BACKGROUND: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited. PURPOSE: To gain a better understanding about GAS meningitis. METHODS: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized. RESULTS: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%. CONCLUSIONS: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death.

Prevalence and genetic diversity of azole-resistant Malassezia pachydermatis isolates from canine otitis and dermatitis: A 2-year study.

Despite previous reports on the emergence of Malassezia pachydermatis strains with decreased susceptibility to azoles, there is limited information on the actual prevalence and genetic diversity of azole-resistant isolates of this yeast species. We assessed the prevalence of azole resistance in M. pachydermatis isolates from cases of dog otitis or skin disease attended in a veterinary teaching hospital during a 2-year period and analyzed the ERG11 (encoding a lanosterol 14-α demethylase, the primary target of azoles) and whole genome sequence diversity of a group of isolates that displayed reduced azole susceptibility. Susceptibility testing of 89 M. pachydermatis isolates from 54 clinical episodes (1-6 isolates/episode) revealed low minimum inhibitory concentrations (MICs) to most azoles and other antifungals, but 11 isolates from six different episodes (i.e., 12.4% of isolates and 11.1% of episodes) had decreased susceptibility to multiple azoles (fluconazole, itraconazole, ketoconazole, posaconazole, ravuconazole, and/or voriconazole). ERG11 sequencing of these 11 azole-resistant isolates identified eight DNA sequence profiles, most of which contained amino acid substitutions also found in some azole-susceptible isolates. Analysis of whole genome sequencing (WGS) results revealed that the azole-resistant isolates from the same episode of otitis, or even different episodes affecting the same animal, were more genetically related to each other than to isolates from other dogs. In conclusion, our results confirmed the remarkable ERG11 sequence variability in M. pachydermatis isolates of animal origin observed in previous studies and demonstrated the value of WGS for disentangling the epidemiology of this yeast species.

We analyzed the prevalence and diversity of azole-resistant Malassezia pachydermatis isolates in a veterinary hospital. A low prevalence of multi-azole resistance (c.10% of isolates and cases) was found. Whole genome and ERG11 sequencing of resistant isolates revealed remarkable genetic diversity.

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.

Two cases of MPO-ANCA-positive hypertrophic pachymeningitis mimicking as intracranial infection.

Hypertrophic pachymeningitis (HP) is a rare disorder marked by thickening of the dura mater due to diverse etiologies. MPO-ANCA-positive HP represents a variant of AAV confined to the central nervous system, distinguished by the presence of serum MPO antibodies. Distinguishing HP triggered by MPO-ANCA from other causes can be challenging.In this study, we present two cases of MPO-ANCA-positive HP initially misdiagnosed as intracranial infections. Case 1 underwent surgery for chronic suppurative otitis media, with histopathological findings revealing inflammatory changes without definitive suppuration. He was presumed to have a secondary intracranial infection resulting from the surgery. However, his condition deteriorated despite two weeks of antibiotic and antiviral treatment. Case 2 presented with headache and was initially suspected of having intracranial Brucellosis given his serum Brucella positivity. Despite treatment for brucellosis, his symptoms persisted, and he developed visual and hearing impairments. Both patients were ultimately diagnosed with MPO-ANCA-positive HP, exhibiting serum MPO antibody positivity. Their symptoms showed improvement with glucocorticoid and immunosuppressive therapy.Based on these observations, we propose that MPO-ANCA-positive HP may initially present as intracranial infection. For HP patients presenting with headache, mastoiditis, otitis media, and visual loss, it is imperative to conduct ANCA antibody-related tests to enhance diagnostic precision.

Interventions to de-implement unnecessary antibiotic prescribing for ear infections (DISAPEAR Trial): protocol for a cluster-randomized trial.

BACKGROUND: Watchful waiting management for acute otitis media (AOM), where an antibiotic is used only if the child's symptoms worsen or do not improve over the subsequent 2-3 days, is an effective approach to reduce antibiotic exposure for children with AOM. However, studies to compare the effectiveness of interventions to promote watchful waiting are lacking. The objective of this study is to compare the effectiveness and implementation outcomes of two pragmatic, patient-centered interventions designed to facilitate use of watchful waiting in clinical practice. METHODS: This will be a cluster-randomized trial utilizing a hybrid implementation-effectiveness design. Thirty-three primary care or urgent care clinics will be randomized to one of two interventions: a health systems-level intervention alone or a health systems-level intervention combined with use of a shared decision-making aid. The health systems-level intervention will include engagement of a clinician champion at each clinic, changes to electronic health record antibiotic orders to facilitate delayed antibiotic prescriptions as part of a watchful waiting strategy, quarterly feedback reports detailing clinicians' use of watchful waiting individually and compared with peers, and virtual learning sessions for clinicians. The hybrid intervention will include the health systems-level intervention plus a shared decision-making aid designed to inform decision-making between parents and clinicians with best available evidence. The primary outcomes will be whether an antibiotic was ultimately taken by the child and parent satisfaction with their child's care. We will explore the differences in implementation effectiveness by patient population served, clinic type, clinical setting, and organization. The fidelity, acceptability, and perceived appropriateness of the interventions among different clinician types, patient populations, and clinical settings will be compared. We will also conduct formative qualitative interviews and surveys with clinicians and administrators, focus groups and surveys of parents of patients with AOM, and engagement of two stakeholder advisory councils to further inform the interventions. DISCUSSION: This study will compare the effectiveness of two pragmatic interventions to promote use of watchful waiting for children with AOM to reduce antibiotic exposure and increase parent satisfaction, thus informing national antibiotic stewardship policy development. CLINICAL TRIAL REGISTRATION: NCT06034080.

Antibacterial effects of chitosan-based hydrogels containing Trachyspermum ammi essential oil on pathogens isolated from dogs with otitis externa.

BACKGROUND: Growing antibiotic resistance has made treating otitis externa (OE) increasingly challenging. On the other hand, local antimicrobial treatments, especially those that combine essential oils (EOs) with nanoparticles, tend to be preferred over systemic ones. It was investigated whether Ajwain (Trachyspermum ammi) EO, combined with chitosan nanoparticles modified by cholesterol, could inhibit the growth of bacterial pathogens isolated from OE cases in dogs. In total, 57 dogs with clinical signs of OE were examined and bacteriologically tested. Hydrogels of Chitosan were synthesized by self-assembly and investigated. EO was extracted (Clevenger machine), and its ingredients were checked (GC-MS analysis) and encapsulated in chitosan-cholesterol nanoparticles. Disc-diffusion and broth Micro-dilution (MIC and MBC) examined its antimicrobial and therapeutic properties. RESULTS: Staphylococcus pseudintermedius (49.3%) was the most common bacteria isolated from OE cases, followed by Pseudomonas aeruginosa (14.7%), Escherichia coli (13.3%), Streptococcus canis (9.3%), Corynebacterium auriscanis (6.7%), Klebsiella pneumoniae (2.7%), Proteus mirabilis (2.7%), and Bacillus cereus (1.3%). The investigation into the antimicrobial properties of Ajwain EO encapsulated in chitosan nanoparticles revealed that it exhibited a more pronounced antimicrobial effect against the pathogens responsible for OE. CONCLUSIONS: Using chitosan nanoparticles encapsulated with EO presents an effective treatment approach for dogs with OE that conventional antimicrobial treatments have not cured. This approach not only enhances antibacterial effects but also reduces the required dosage of antimicrobials, potentially preventing the emergence of antimicrobial resistance.

Topical administration of S. salivarius 24SMB-S. oralis 89a in children with adenoidal disease: a double-blind controlled trial.

Chronic adenoiditis (CA) is generally sustained by some infectious foci mainly located within the nasopharynx or in the deep adenoidal pads and it is characterized by a complex interplay between bacterial species. The aim of this study was to assess the efficacy and safety of the topical nasal administration of a probiotic compound based on S. salivarius 24SMB and S. oralis 89a in children with CA in terms of reduction in: the number of acute adenoidal infections (primary outcome), and in the blockage of the nasopharynx space by hypertrophic adenoids (secondary outcome). A prospective, double-blind, 1:1 randomized controlled study was performed to test the effectiveness of a 90-day treatment with Rinogermina spray (DMD ITALIA s.r.l, Rome), 1 puff each nostril twice a day for 90 days, to nasal spray placebo in children with CA (in terms of number of acute exacerbations and blockage of nasopharynx space assessed after 90 days of treatment- T1, and 90 days later- T2). The final analysis was based on 152 children (males = 48.0%; mean age = 49.2 ± 14.1 months). Compared to the baseline, no significant differences in terms of number of acute exacerbations at T1 and T2 follow-up visits were detected in both groups. After treatment, a significant reduction in the blockage of nasopharynx space by hypertrophic adenoids (0.002 < p-value < 0.007) compared to the baseline was attested in the study group at T1 and T2, but not in the control group. CONCLUSIONS: Our findings document a positive effect of Rinogermina spray in achieving reduction in the blockage of nasopharynx space by hypertrophic adenoids, thus suggesting that its use into the integrated therapeutic management of children with CA could be of a certain utility. WHAT IS KNOWN: • Chronic adenoiditis in children results from an imablance in baterial homeostasis at the nasophaynx, with impairment in respiratory microbiota. • The modulatory effect of target transnasal bacteriotheray by means of S. salivarius has been considered in children with chronic adenoiditis in children with recurrent acute otitis media with preliminary positive results. WHAT IS NEW: • This randomized controlled study, specifically designed on a cohrt of children with chronic adenoiditis, documents a certain effectiveness of the probiotic treatment in achieving a reduction in the grade of adenoidal hypertropy, compared to placebo.

Topical or oral antibiotics in childhood acute otitis media and ear discharge: a randomized controlled non-inferiority trial.

BACKGROUND: Current guidance suggests oral antibiotics can be considered for children with acute otitis media (AOM) and ear discharge, but there is an absence of evidence regarding the relative effectiveness of antibiotic-corticosteroid eardrops. AIM: To establish whether antibiotic-corticosteroid eardrops are non-inferior to oral antibiotics in children with AOM and ear discharge. DESIGN AND SETTING: Open randomized controlled non-inferiority trial set in Dutch primary care. METHODS: Children were randomized to hydrocortisone-bacitracin-colistin eardrops (five drops, three times per day in the discharging ear(s)) or amoxicillin suspension (50 mg per kilogram of body weight per day, divided over three doses administered orally) for 7 days. The primary outcome was the proportion of children with resolution of ear pain and fever at day 3. RESULTS: Between December 2017 and March 2023, 58 of the planned 350 children were recruited due to slow accrual for various reasons. Children assigned to eardrops (n = 26) had lower resolution rates of ear pain and fever at 3 days compared to those receiving oral antibiotics (n = 31): 42% vs 65%; adjusted risk difference 20.3%, 95% confidence interval -5.3% to 41.9%), longer parent-reported ear discharge (6 vs 3 days; P = .04), and slightly higher mean ear pain scores (Likert scale 0-6) over days 1-3 (2.1 vs 1.4, P = .02), but received fewer oral antibiotic courses in 3months (11 for 25 children vs 33 for 30 children), and had less GI upset and rash (12% vs 32% and 8% vs 16%, respectively). CONCLUSION: Early termination stopped us from determining non-inferiority of antibiotic-corticosteroid eardrops. Our limited data, requiring confirmation, suggest that oral antibiotics may be more effective than antibiotic-corticosteroid eardrops in resolving symptoms and shortening the duration of ear discharge.

A rapid simultaneous antigen detection of Haemophilus influenzae and Streptococcus pneumoniae for predicting the prognosis of acute otitis media.

BACKGROUND: Rapid identification of causative bacteria in treatment of acute otitis media (AOM) is of paramount importance for appropriate antibiotic use. MATERIALS AND METHODS: This prospective observational study was conducted in 15 hospitals and clinics in Japan between 2018 and 2020. A new rapid antigen test kit (AOS-116), which simultaneously detects antigens for Streptococcus pneumoniae (Sp) and Haemophilus influenzae (Hi), was applied for middle ear fluids (MEFs) and nasopharyngeal secretions (NPSs) in patients with moderate to severe AOM. We investigated relationship between the results of rapid test, severity at initial visit, and clinical course. RESULTS: Regarding performance accuracy based on culture results, AOS-116 showed 1) high (>80%) sensitivity, specificity, and negative predictive value (NPV) in MEFs for both antigens, 2) high sensitivity, specificity, and positive predictive value (PPV) in NPSs for Hi antigen, and 3) high specificity, and PPV in NPSs for Sp antigen. Regarding predictive value of nasopharyngeal culture and antigen detection for causative middle ear pathogens, similar results were observed between AOS-116 and culture, which was characterized with high sensitivity and NPV for both pathogens. MEFs/NPSs positive for Hi antigen were significantly associated with eardrum findings, and severity. MEFs/NPSs positive for pneumococcal antigen were significantly associated with severity of otalgia, fever, and otorrhea. Among patients with prior antimicrobial treatment, improvement tended to be slower in cases positive for Hi than in cases negative. CONCLUSION: The rapid antigen detection test is useful as a decision-making tool for prescribing antimicrobial agents and may play an important role in promoting appropriate antimicrobial use.

Factors affecting the antimicrobial changes during treatment for acute otitis media in Japan: A retrospective cohort study using classification and regression trees (CART) analysis.

OBJECTIVES: Factors that affect the change of first-line antimicrobial agents were investigated to further promote their appropriate use. METHODS: This descriptive study used an electronic medical records database. Total 16,353 of the 199,896 patients enrolled between 1996 and 2019 met the inclusion criteria and formed the overall pediatric acute otitis media (AOM) cohort. The factors leading to the change in first-line antimicrobial agents within 14 days were analyzed using classification and regression trees (CART) analysis. RESULTS: This antimicrobial treatment cohort, involved 4860 cases of AOM alone and 9567 cases of AOM with other diseases. The size of the medical facility based on number of beds and historical duration of patient registration impacted on antimicrobial changes. CONCLUSIONS: The current results show that hospital-wide or nation-wide antimicrobial stewardship promotion could be the most influencing factor for antimicrobial changes. Particularly in cases of AOM where other diseases coexist, a more accurate diagnosis and definition of treatment failure of first-line drug are suggested to be important while establishing future treatment strategies. The current study is important to promote appropriate antimicrobial use for AOM treatment.

High risk and low prevalence diseases: Acute mastoiditis.

INTRODUCTION: Acute mastoiditis is a serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of mastoiditis, including the presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: Acute mastoiditis most commonly affects pediatric patients and is a suppurative infection of the mastoid air cells. It is often associated with otitis media, and common bacteria include Streptococcus and Staphylococcus. History and examination may reveal tympanic membrane erythema, pinna protrusion, postauricular erythema, mastoid tenderness with palpation, external canal swelling, otorrhea, fever, and malaise. The disease should be suspected in those who fail treatment for otitis media and those who demonstrate the aforementioned abnormalities on examination and systemic symptoms. Laboratory analysis may reveal evidence of systemic inflammation, but a normal white blood cell count and other inflammatory markers should not be used to exclude the diagnosis. Computed tomography (CT) of the temporal bones with intravenous contrast is the recommended imaging modality if the clinician is unsure of the diagnosis. CT may also demonstrate complications. Treatment includes antibiotics such as ampicillin-sulbactam or ceftriaxone as well as otolaryngology consultation. Complications may include subperiosteal and intracranial abscess, deep neck abscess, facial nerve palsy, meningitis/encephalitis, venous sinus thrombosis, and seizures. CONCLUSIONS: An understanding of acute mastoiditis can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

The long and the short of pediatric emergency department antibiotic prescribing: A retrospective observational study.

BACKGROUND: Most antibiotics prescribed to children are provided in the outpatient and emergency department (ED) settings, yet these prescribers are seldom engaged by antibiotic stewardship programs. We reviewed ED antibiotic prescriptions for three common infections to describe current prescribing practices. METHODS: Prescription data between 2018 and 2021 were extracted from the electronic records of children discharged from the Children's Hospital of Eastern Ontario ED with urinary tract infection (UTI), community acquired pneumonia (CAP), and acute otitis media ≥2 years of age (AOM). Antibiotic choice, duration, as well as the provider's time in practice and training background were collected. Antibiotic durations were compared with Canadian guideline recommendations to assess concordance. Provider-level prescribing practices were analyzed using k-means cluster analysis. RESULTS: 10,609 prescriptions were included: 2868 for UTI, 2958 for CAP, and 4783 for AOM. Guideline-concordant durations prescribed was generally high (UTI 84.9%, CAP 94.0%, AOM 52.8%), a large proportion of antibiotic-days prescribed were in excess of the minimally recommended duration for each infection (UTI 16.8%, 19.3%, AOM 25.5%). Cluster analysis yielded two clusters of prescribers, with those in one cluster more commonly prescribing durations at the lower end of recommended interval, and the others more commonly prescribing longer durations for all three infections reviewed. No statistically significant differences were found between clusters by career stage or training background. CONCLUSIONS: While guideline-concordant antibiotic prescribing was generally high, auditing antibiotic prescriptions identified shifting prescribing towards the minimally recommended duration as a potential opportunity to reduce antibiotic use among children for these infections.