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.

Biofilm formation and EPS production enhances the bioremediation potential of Pseudomonas species: a novel study from eutrophic waters of Dal lake, Kashmir, India.

The present study was conducted with the aim of isolation and identification of the biofilm-forming denitrifying Pseudomonas bacterial strains from eutrophic waters of Dal lake, India, followed by the study of inter-relation of biofilm formation and denitrification potential of Pseudomonas strains. The bacterial strains were characterized by morphological observations and identified using 16S rDNA sequencing followed by the quantification of biofilm formation of these st by crystal violet (CV) assay using 96-well microtiter plate and extracellular polymeric substance (EPS) extraction. Lastly, the nitrate-reducing potential of all Pseudomonas species was studied. Our evaluation revealed that four different Pseudomonas species were observed to have the biofilm-forming potential and nitrate-reducing properties and the species which showed maximum biofilm-forming potential and maximum EPS production exhibited higher nitrate-removing capacity. Moreover, P. otitis was observed to have the highest denitrification capacity (89%) > P. cedrina (83%) > P. azotoform (79%) and the lowest for P. peli (70%). These results clearly signify a positive correlation of biofilm-forming capacity and nitrate-removing ability of Pseudomonas species. This study has for the first time successfully revealed the bioremediation potential of P. otitis, P. cedrina, P. azotoform, and P. peli species, thus contributing to the growing list of known nitrate-reducing Pseudomonas species. Based upon the results, these strains can be extrapolated to nitrate-polluted water systems for combating water pollution.

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.

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.

Intracranial complications of sinogenic and otogenic infections in children: an ESPN survey on their occurrence in the pre-COVID and post-COVID era.

BACKGROUND: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017-2019), COVID (2020-2021), and post-COVID period (2022-June 2023) looking for possible epidemiological and/or clinical changes. MATERIAL AND METHODS: An English language questionnaire was sent to ESPN members about year of the event, patient's age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. RESULTS: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses and middle ear/mastoid were the most involved primary site of infection (71% and 27%, respectively), while extradural or subdural empyema and brain abscess were the most common ICSO (73% and 17%, respectively). Surgery was required in 95% of cases (neurosurgical and ENT procedure in 71% and 62% of cases, respectively) while antibiotics in 99% of cases. After a 12.4-month follow-up, a full clinical and radiological recovery was obtained in 85% and 84% of cases, respectively. The mortality rate was 2.7%. CONCLUSIONS: These results suggest that the occurrence of ICSO was significantly increased after the pandemic. Such an increase seems to be related to the indirect effects of the pandemic (e.g., immunity debt) rather than to a direct effect of COVID infection or to seasonal fluctuations. ICSO remain challenging diseases but the pandemic did not affect the management strategies nor their prognosis. The epidemiological change of sinusitis/otitis and ICSO should alert about the appropriate follow-up of children with sinusitis/otitis.

Nanocatalysts as fast and powerful medical intervention: Bridging cochlear implant therapies and advanced modelling using Hidden Markov Models (HMMs) for effective treatment of inner ear infections.

As human population growth and waste from technologically advanced industries threaten to destabilise our delicate ecological equilibrium, the global spotlight intensifies on environmental contamination and climate-related changes. These challenges extend beyond our external environment and have significant effects on our internal ecosystems. The inner ear, which is responsible for balance and auditory perception, is a prime example. When these sensory mechanisms are impaired, disorders such as deafness can develop. Traditional treatment methods, including systemic antibiotics, are frequently ineffective due to inadequate inner ear penetration. Conventional techniques for administering substances to the inner ear fail to obtain adequate concentrations as well. In this context, cochlear implants laden with nanocatalysts emerge as a promising strategy for the targeted treatment of inner ear infections. Coated with biocompatible nanoparticles containing specific nanocatalysts, these implants can degrade or neutralise contaminants linked to inner ear infections. This method enables the controlled release of nanocatalysts directly at the infection site, thereby maximising therapeutic efficacy and minimising adverse effects. In vivo and in vitro studies have demonstrated that these implants are effective at eliminating infections, reducing inflammation, and fostering tissue regeneration in the ear. This study investigates the application of hidden Markov models (HMMs) to nanocatalyst-loaded cochlear implants. The HMM is trained on surgical phases in order to accurately identify the various phases associated with implant utilisation. This facilitates the precision placement of surgical instruments within the ear, with a location accuracy between 91% and 95% and a standard deviation between 1% and 5% for both sites. In conclusion, nanocatalysts serve as potent medicinal instruments, bridging cochlear implant therapies and advanced modelling utilising hidden Markov models for the effective treatment of inner ear infections. Cochlear implants loaded with nanocatalysts offer a promising method to combat inner ear infections and enhance patient outcomes by addressing the limitations of conventional treatments.

Genetic diversity of Staphylococcus aureus isolated from ear infections in Iran: Emergence of CC8/ST239-SCCmec III as major genotype.

Increase in antibiotic resistance in Staphylococcus aureus isolated from ear infection is a serious public health problem. The objective of this investigation was to determine the antibacterial resistance profile and genetic variability of the S. aureus isolated from adult patients with otitis externa (OE) and otitis media (OM) infections, Tehran- Iran. The disk diffusion was employed to detect the susceptibility of 45 S. aureus strains. Biofilm production was evaluated by microtiter plate assay. Genetic diversity of the isolates was determined by staphylococcal cassette SCCmec, spa, and MLST techniques. Resistance to mupirocin and vancomycin were identified in 40 and 2.2% of isolates. Out of the 45 S. aureus isolates, 41 (91.2%) strains were considered as positive biofilm strains at different levels. According to our results, S. aureus isolated from OM (44.4%, 20/45) were including CC8/ST239-SCCmecIII corresponded to spa types t860, t030, t037, t234, t421 (70%, 14/20) and CC/ST30-SCCmecIV corresponded to spa types t605 and t019 (30%, 6/20) while S. aureus isolated from OE (55.6%, 25/45) were including CC/ST30-SCCmecIV corresponded to spa types t605, t345 and t1130 (52%, 13/25), CC/ST22-SCCmecIV corresponded to spa type t790 (20%, 5/25), CC8/ST8-SCCmecIV corresponded to spa type t008 (16%, 4/25), and CC/ST45-SCCmecIV corresponded to spa types t004 and t038 (12%, 3/25). This study highlighted genetic variability and strong biofilm formation ability among our isolates revealing its crucial role in enhancing the resistance of this bacteria to drugs. Thus, it is necessary to continue the epidemiological analysis to improve the control of ear infections related to S. aureus.

Carnobacterium maltaromaticum associated with meningoencephalitis and otitis in stranded common thresher sharks (Alopias vulpinus).

Juvenile common thresher sharks (Alopias vulpinus) have been recently stranding along the California coastline. Using Illumina sequencing of the bacterial 16S rRNA gene along with necropsy, cytological, bacteriological, and histological techniques, we screened microbial communities and described lesions characterizing affected sharks with the purpose of identifying potential pathogen sources and pathologic processes. Histopathological assessment of moribund sharks revealed severe meningoencephalitis, as previously described in stranded salmon sharks (Lamna ditropis), along with inflammation of the inner ear and subcutaneous tissues surrounding the endolymphatic ducts. Furthermore, inflamed areas were characterized by the prevalence of Carnobacterium maltaromaticum, suggesting this bacterium as a potential pathogen that gains access to the inner ear through the endolymphatic ducts, with subsequent spread into the brain. The absence or low abundance of this bacterium in the spiral valve in both healthy and infected sharks suggests that Carnobacterium is not a commensal member of their digestive communities and the spiral valve is unlikely to be the source of the pathogen. Furthermore, phylogenetic analysis suggests that C. maltaromaticum strains isolated from diseased sharks have minimal genetic variation and differ from other strains originating from food or diseased teleosts. While a C. maltaromaticum-like organism has previously been associated with meningoencephalitis in salmon shark strandings, this is the first study to report common thresher shark strandings associated with C. maltaromaticum, involving the endolymphatic ducts as portals of entry to the brain.

In vitro antibacterial and antibiofilm effects of cold atmospheric microwave plasma against Pseudomonas aeruginosa causing canine skin and ear infections.

BACKGROUND: Pseudomonas aeruginosa is an opportunist pathogen that causes purulent inflammation in the skin and in the ears of dogs. Among the various virulence factors of P. aeruginosa, biofilms have been reported to result in antibiotic resistance, leading to therapeutic limitations. Cold atmospheric microwave plasma (CAMP) is known to have a high antimicrobial effect, which causes physical cell wall rupture and DNA damage. HYPOTHESIS/OBJECTIVES: The objective of this study was to evaluate the antibacterial and antibiofilm effects of CAMP against planktonic bacteria and the biofilm of P. aeruginosa. METHODS AND MATERIALS: The antibacterial effect of CAMP against P. aeruginosa ATCC10145 and clinical isolates (n = 30) was evaluated using the colony count method. We also assessed the effect of CAMP on biofilm of P. aeruginosa ATCC strain by the colony count method, water-soluble tetrazolium salt (WST) assay and confocal laser scanning microscopy (CLSM). RESULTS: The complete eradication of P. aeruginosa (ATCC strain and clinical isolates) was achieved within 120 s at 50 W, and clinical isolates required 60 s shorter than the ATCC strain for complete eradication at 50 W. We also confirmed the time-dependent bactericidal effect of CAMP at 50 W against ATCC strain biofilm. CONCLUSIONS AND CLINICAL IMPORTANCE: CAMP was effective against both planktonic bacteria and biofilm formation of P. aeruginosa. However, further studies on in vivo efficacy and safety in canine skin and ears are necessary to fully validate its clinical application.

Pseudomonas aeruginosa susceptibility, antibiogram and clinical interpretation, and antimicrobial prescribing behaviors for dogs with otitis in the Midwestern United States.

Pseudomonas aeruginosa (P. aeruginosa) can cause otitis in dogs that is nonresponsive to empirical therapy. This study evaluated P. aeruginosa isolates (N = 216) from canine ear swabs submitted to the Kansas State Veterinary Diagnostic Laboratory from 2018-2020 to create an antibiogram and minimum inhibitory concentration distributions using Clinical Laboratory Standards Institutes breakpoints. Multidrug resistance was defined as non-susceptibility to ≥1 drug from ≥3 antimicrobial classes. Submitting veterinarians (N = 83) were invited to complete a survey about antimicrobial use and otitis management. Susceptibility was higher for aminoglycosides [gentamicin (82%, 177/216) and amikacin (81%, 175/216)] than fluoroquinolones [marbofloxacin (67%, 145/216), enrofloxacin (32%, 70/216), and orbifloxacin (18%, 39/216)]. Most responding veterinarians (54%, 15/28) prescribe topical aminoglycosides as first-line therapy for canine otitis, but 71% (15/21) prescribe fluoroquinolones if rods are seen cytologically. Ceftazidime, imipenem, and piperacillin-tazobactam showed high susceptibility and are used rarely. Multidrug resistance was present in 13% (28/216) of isolates. Based on in vitro susceptibility, topical aminoglycosides might be more effective than fluoroquinolones for P. aeruginosa otitis, but efficacy studies are required. Susceptibility testing is encouraged for cases not responding to empirical therapy but has limitations because topical preparations have high concentrations and otic breakpoints are not available.

Personal and early life factors associated with new-onset asthma, remission, and persistence of asthma in a 2-year follow-up of schoolchildren.

OBJECTIVE: The natural course of childhood asthma, after its onset, is characterized by periods of persistence, relapse and remission. To investigate personal and early life factors associated with new-onset asthma, persistence and remission among children. METHODS: The study was conducted in the province of Saskatchewan, Canada. Children in grades Kindergarten to Grade 8 (ages 5-14 years) participated in a cross-sectional study in 2013. In 2015, we approached those who gave consent in 2013 to be re-contacted, creating a prospective cohort. Data were collected using questionnaires in both years. Participants in 2013 who also had data in 2015 (25%: n = 324/1,348) had their asthma status reclassified and longitudinal descriptors were applied: "no asthma", "new-onset asthma", "persistent" or "remission". Personal and early life factors associations with asthma outcomes in 2015 were evaluated. RESULTS: Among those without asthma in 2013 (n = 245), the incidence of new-onset asthma in 2015 was 7.2%. Among those with asthma in 2013 (n = 79), 47.1% had remission and 52.9% had persistent asthma in 2015. Parental history of asthma (adjusted odds ratio (aOR): 4.99; 95% confidence interval (CI): 1.88-28.27), early life respiratory infection (aOR: 1.92; 95%CI: 1.47-7.88), early life allergy [aOR: 6.39; 95%CI: 1.34-30.58) and early life infection (aOR: 4.99; 95%CI: 1.19-20.93) were associated with new onset asthma. Similarly, while parental history of asthma (aOR: 1.13; 95%CI: 0.29-4.34), early life respiratory infection (aOR: 2.71; 95%CI: 0.70-10.45), and early life ear infection (aOR: 1.34; 95%CI: 0.36-5.05) were also positively association with persistent asthma, the associations were not statistically significant. CONCLUSION: Parental history of asthma, early life respiratory infection and allergy might not only influence the onset of childhood asthma but also be associated with asthma persistence.

Comparison of antimicrobial prescription patterns in calves in Switzerland before and after the launch of online guidelines for prudent antimicrobial use.

BACKGROUND: The increasing threat of bacterial resistance promotes the need for antibiotic stewardship programs to foster responsible antimicrobial use. Therefore, guidelines for prudent use supported by an online stewardship tool (AntibioticScout.ch) were introduced in Switzerland in December 2016. They recommend (with decreasing preference) a first, second or third line antimicrobial for treatment. The objective of this study was to evaluate antimicrobial prescriptions for Swiss calves before (2016) and after (2018) the launch of these guidelines. Cases of calves with pneumonia, diarrhea and otitis from a university hospital and eight private practices in Switzerland were included. Data on anamnesis, clinical findings, diagnostic work-up and treatment were collected. Type and percentages [95% confidence interval] of antimicrobial prescriptions were compared between 2016 and 2018. RESULTS: Of the total number of calves, 88.2% [85.4-90.6] in 2016 (n = 625) and 88.4% [85.7-90.7] in 2018 (n = 655) were treated with antibiotics. The use of highest priority critically important antimicrobials (HPCIAs) decreased from 52.7% [48.6-56.9] in 2016 to 38.0% [34.2-41.9] in 2018; this decrease was found at the university hospital and in private practice and in cases with pneumonia and diarrhea. Particularly the use of fluoroquinolones decreased (2016: 43.1% [39.2-47.2]; 2018: 31.1% [27.6-34.8]). Overall, the number of first line treatments increased from 12.8% [10.4-15.6] in 2016 to 20.2% [17.3-23.4] in 2018. In cases of pneumonia, first line treatments increased (2016: 15.3% [11.6-19.9]; 2018: 26.5% [21.8-31.9]) and third line treatments decreased (2016: 43.5% [38.0-49.3]; 2018: 27.9% [23.1-33.3]); this was seen at the university hospital, whereas in private practice only a decrease of third line treatments was observed. In cases of diarrhea, more second line at the expense of unlisted antimicrobials were prescribed at the university hospital in 2018. Antimicrobial treatment of calves with otitis did not change from 2016 to 2018. CONCLUSIONS: After the introduction of AntibioticScout.ch, more prudent use was observed in the treatment of calves with pneumonia and diarrhea as less HPCIAs, particularly fluoroquinolones, and more first line antimicrobials were prescribed. However, the overall frequency of antimicrobial treatment did not change and the use of HPCIAs was still common in 2018, especially in private practices. Therefore, further antimicrobial stewardship activities are necessary.

Pilot study of dogs with suppurative and non-suppurative Malassezia otitis: A case series.

BACKGROUND: Rarely, Malassezia otitis presents as a painful, erosive otitis with an otic discharge containing Malassezia and neutrophils on cytology. There are no published reports of this type of suppurative Malassezia otitis (SMO). The role of Malassezia hypersensitivity in otitis is still unknown, and no association has been demonstrated with SMO. We compared Malassezia IgE levels, intradermal test and histology changes in SMO dogs with the more conventional Malassezia otitis (MO) presentation. RESULTS: Three dogs (case 1, case 2 and case 3) were diagnosed with SMO, one dog (case 4) was diagnosed with unilateral MO and unilateral SMO, and one dog (case 5) was diagnosed with MO. Only one case (case 4) with SMO/MO had a positive Intradermal Allergy Test (IDAT) and elevated IgE levels for Malassezia. Histopathology findings from SMO revealed: interface dermatitis (case 1 and 3), lymphocytic dermatitis (case 2) and chronic hyperplastic eosinophilic and lymphoplasmacytic dermatitis (case 4). Histopathology findings from MO showed perivascular dermatitis (case 4 and 5). All the cases were treated successfully. CONCLUSIONS: SMO presents with a distinct clinical phenotype in comparison with conventional MO. No consistent aetiology could be isolated. In these clinical cases it is possible that previous treatments could have influenced the results. More research is needed to understand the possible aetiologies and the pathogenesis of SMO.

Association of in utero antibiotic exposure on childhood ear infection trajectories: Results from a national birth cohort study.

AIM: Most prescribed medicines during pregnancy are antibiotics, with unknown effects on a fetus and on the infant's acquired microbiome. This study investigates associations between in utero antibiotic exposure and ear infection trajectories over the first decade of life, hypothesising effects on early or persistent, rather than later-developing, ear infections. METHODS: Design and participants: The Longitudinal Study of Australian Children birth cohort recruited a nationally-representative sample of 5107 infants in 2004. MEASURES: Mothers reported antibiotic use in pregnancy when a child was 3-21 months old (wave 1), and ongoing problems with ear infection every 2 years spanning ages 0-1 to 10-11 years (waves 1-6). ANALYSIS: Latent class models identified ear infection trajectories, and univariable and multivariable multinomial logistic regression determined odds of adverse trajectories by antibiotic exposure. RESULTS: A total of 4500 (88.1% of original sample) children contributed (mean baseline age 0.7 years; 51.3% boys); 10.4% of mothers reported antibiotic use in pregnancy. Four probability trajectories for ear infection emerged: 'consistently low' (86.2%), 'moderate to low' (5.6%), 'low to moderate' (6.7%) and 'consistently high' (1.4%). Antibiotic use in pregnancy was associated with children following 'consistently high' (adjusted odds ratio 2.04, 95% confidence interval 1.08-3.88, P = 0.03) and 'moderate to low' (adjusted odds ratio 1.78, 95% confidence interval 1.25-2.53, P = 0.001) trajectories. CONCLUSIONS: Antibiotic use in pregnancy is associated with an increased risk of persistent and early childhood ear infections. This highlights the wisdom of cautious antibiotic use during pregnancy, and the need for the study of potential mechanisms underlying these associations.

Effect of metaphylactic administration of tildipirosin on the incidence of pneumonia and otitis and on the upper respiratory tract and fecal microbiome of preweaning Holstein calves.

The objectives of this study were to evaluate the effect of the metaphylactic use of a semi-synthetic long-acting macrolide (tildipirosin) on the prevention of pneumonia and otitis in preweaning Holstein calves, as well as its effects on the microbiome of their upper respiratory tract (URT) and feces. Newborn healthy Holstein heifers, collectively housed, were randomly allocated to 1 of 2 treatment groups: treatment (TRT; n = 932) or control (CTR; n = 927). Calves in the TRT group received a single subcutaneous injection of 4 mg/kg tildipirosin (Zuprevo, Merck Animal Health) at 7 ± 7 d of life. Calves in the CTR group received no drug injection. All enrolled calves were evaluated from 1 to 63 ± 3 d of life (weaning age) and monitored daily for any adverse health events during this period. Daily physical examination was performed to diagnose pneumonia and otitis, and body weight was measured weekly in all animals. From a randomly selected subset of 217 calves, blood samples for biochemical variables analysis and swabs were collected weekly from the URT and rectum for analysis of the nasal and fecal microbiome, respectively, via next-generation sequencing of the 16S rRNA gene. Total bacterial load was evaluated using quantitative PCR. In addition, another subset of 26 calves was randomly selected and fecal swabs were collected in a more intensive sampling to investigate the short-term effect of tildipirosin administration on the fecal microbiome. We performed general mixed linear models and logistic regression to analyze continuous and binary outcomes, respectively. Tildipirosin metaphylaxis reduced the incidence of otitis (CTR = 47.03%; TRT = 37.55%) and tended to reduce the incidence of pneumonia (CTR = 20.71%; TRT = 17.38%) and the overall mortality risk (CTR = 6.69%; TRT = 4.94%). We observed no significant differences between groups for mortality due to pneumonia (CTR = 0.86%; TRT = 0.97%) or mortality due to otitis (CTR = 2.05%; TRT = 1.39%). Calves in the TRT group had a higher average daily gain than calves in the CTR group. Furthermore, metaphylaxis had no significant effects on the total bacterial load, genus, or phylum analysis of the fecal microbiome from the 2 subset groups. However, for the URT microbiota, we observed a significant decrease in total bacterial load for the TRT group compared to the CTR group 1 week after metaphylactic injection. Tildipirosin metaphylaxis decreased the mean relative abundance of the genera Mannheimia, Moraxella, and Pasteurella but significantly increased the mean relative abundance of Mycoplasma. Although tildipirosin had no positive effect on Mycoplasma, it reduced the mean relative abundance of important pathogenic bacteria in the URT and had positive effects for the control of otitis. The metaphylactic use of tildipirosin can be a suitable strategy for the control of otitis on farms with a high prevalence of this disease.

Antibacterial Polysiloxane Polymers and Coatings for Cochlear Implants.

Within this study, new materials were synthesized and characterized based on polysiloxane modified with different ratios of N-acetyl-l-cysteine (NAC) and crosslinked via UV-assisted thiol-ene addition, in order to obtain efficient membranes able to resist bacterial adherence and biofilm formation. These membranes were subjected to in vitro testing for microbial adherence against S. pneumoniae using standardized tests. WISTAR rats were implanted for 4 weeks with crosslinked siloxane samples without and with NAC. A set of physical characterization methods was employed to assess the chemical structure and morphological aspects of the new synthetized materials before and after contact with the microbiological medium.

A mouse ear skin model to study the dynamics of innate immune responses against Staphylococcus aureus biofilms.

BACKGROUND: Staphylococcus aureus is a human pathogen that is a common cause of nosocomial infections and infections on indwelling medical devices, mainly due to its ability to shift between the planktonic and the biofilm/sessile lifestyle. Biofilm infections present a serious problem in human medicine as they often lead to bacterial persistence and thus to chronic infections. The immune responses elicited by biofilms have been described as specific and ineffective. In the few experiments performed in vivo, the importance of neutrophils and macrophages as a first line of defence against biofilm infections was clearly established. However, the bilateral interactions between biofilms and myeloid cells remain poorly studied and analysis of the dynamic processes at the cellular level in tissues inoculated with biofilm bacteria is still an unexplored field. It is urgent, therefore, to develop biologically sound experimental approaches in vivo designed to extract specific immune signatures from the planktonic and biofilm forms of bacteria. RESULTS: We propose an in vivo transgenic mouse model, used in conjunction with intravital confocal microscopy to study the dynamics of host inflammatory responses to bacteria. Culture conditions were created to prepare calibrated inocula of fluorescent planktonic and biofilm forms of bacteria. A confocal imaging acquisition and analysis protocol was then drawn up to study the recruitment of innate immune cells in the skin of LysM-EGFP transgenic mice. Using the mouse ear pinna model, we showed that inflammatory responses to S. aureus can be quantified over time and that the dynamics of innate immune cells after injection of either the planktonic or biofilm form can be characterized. First results showed that the ability of phagocytic cells to infiltrate the injection site and their motility is not the same in planktonic and biofilm forms of bacteria despite the cells being considerably recruited in both cases. CONCLUSION: We developed a mouse model of infection to compare the dynamics of the inflammatory responses to planktonic and biofilm bacteria at the tissue and cellular levels. The mouse ear pinna model is a powerful imaging system to analyse the mechanisms of biofilm tolerance to immune attacks.

Importance of signal intensity on T1-weighted spin-echo sequence for the diagnosis of chronic cholesteatomatous otitis.

OBJECTIVE: The aim of our study was to evaluate the importance of a non-injected T1-weighted spin-echo sequence (T1WSE) combined with a non-echo-planar diffusion-weighted (non-EPDW) sequence for the pre-operative detection of cholesteatoma by the radiologist on MRI, compared to surgery. MATERIALS AND METHODS: In this retrospective case review, 113 patients with chronic otitis underwent surgery (gold standard) for a clinical suspicion of cholesteatoma. Our primary outcome was to compare non-EPDW images + a contrast-free T1WSE sequence for cholesteatoma detection. Our secondary outcome was to quantify the signal intensity value of the suspected lesions, relative to the signal intensity of the cerebellum (Sic) to calculate Signal Intensity Ratios (SIR = SI/Sic). The SIR values of cholesteatomatous and non-cholesteatomatous tissue were compared to surgical findings. Receiver-operating characteristic curve analysis determined an optimum SIR cut-off value for the prediction of cholesteatoma. RESULTS: The sensitivity (96.9%) of non-EPDW for the diagnosis of cholesteatoma was high, with good specificity (74.2%), and increased to 85.5% when combined to a T1WSE sequence. Additionally, the mean SIR values (on T1WSE) of cholesteatoma were significantly lower than non-cholesteatomatous tissue (p < 0.05). When nonEPDW and T1WSE were combined, a cut-off SIR value < 1.04, diagnosed cholesteatoma pre-operatively with very high specificity and sensibility (92.7% and 90.3% respectively). CONCLUSION: Our study showed that combining a nonEPDW sequence with the quantitative analysis of contrast-free T1W SE sequence in pre-operative patients enables the correct diagnosis of cholesteatoma with good sensitivity and specificity (> 90%) and reduces risks of false-positive cases for surgeons.

Children with otitis attending emergency primary health care units following introduction of pneumococcal vaccine. / Barn på legevakt med ørebetennelse etter innføring av pneumokokkvaksinen.

BACKGROUND: Otitis is a frequently occurring condition in young children and involves considerable use of antibiotics. The most common bacterial cause is pneumococci. The pneumococcal vaccine was introduced as part of the Childhood Immunisation Programme in Norway in 2006. The purpose of the study was to investigate whether this vaccination may have reduced the number of otitis cases presenting at emergency primary health care units. MATERIAL AND METHOD: The material consists of data from all electronic reimbursement claims from emergency primary health care doctors in the period 2006-18. Annual consultation rates were calculated for children aged 0-5 years attending an emergency primary health care unit, both in total and due to otitis. Registration of vaccination coverage in this age group began in 2006. RESULTS: The total consultation rate fell from 674 per 1000 inhabitants in 2006 to 502 in 2018 (a relative reduction of 26 %). The consultation rate for otitis fell from 44 per 1000 inhabitants to 21 (a relative reduction of 52 %). While the total rate fell steadily throughout the period, the reduction in consultation rates for otitis began to fall in 2011, when vaccination coverage in this group was over 90 %. INTERPRETATION: The pneumococcal vaccine may have reduced the number of children presenting with otitis at an emergency primary health care unit.

Evidence for a dynorphin-mediated inner ear immune/inflammatory response and glutamate-induced neural excitotoxicity: an updated analysis.

Acoustic overstimulation (AOS) is defined as the stressful overexposure to high-intensity sounds. AOS is a precipitating factor that leads to a glutamate (GLU)-induced Type I auditory neural excitotoxicity and an activation of an immune/inflammatory/oxidative stress response within the inner ear, often resulting in cochlear hearing loss. The dendrites of the Type I auditory neural neurons that innervate the inner hair cells (IHCs), and respond to the IHC release of the excitatory neurotransmitter GLU, are themselves directly innervated by the dynorphin (DYN)-bearing axon terminals of the descending brain stem lateral olivocochlear (LOC) system. DYNs are known to increase GLU availability, potentiate GLU excitotoxicity, and induce superoxide production. DYNs also increase the production of proinflammatory cytokines by modulating immune/inflammatory signal transduction pathways. Evidence is provided supporting the possibility that the GLU-mediated Type I auditory neural dendritic swelling, inflammation, excitotoxicity, and cochlear hearing loss that follow AOS may be part of a brain stem-activated, DYN-mediated cascade of inflammatory events subsequent to a LOC release of DYNs into the cochlea. In support of a DYN-mediated cascade of events are established investigations linking DYNs to the immune/inflammatory/excitotoxic response in other neural systems.