Ear microbiota and middle ear disease: a longitudinal pilot study of Aboriginal children in a remote south Australian setting

Background Otitis media (OM) is a major disease burden in Australian Aboriginal children, contributing to serious long-term health outcomes. We report a pilot analysis of OM in children attending an outreach ear and hearing clinic in a remote south Australian community over a two-year period. Our study focuses on longitudinal relationships between ear canal microbiota characteristics with nasopharyngeal microbiota, and clinical and treatment variables. Results Middle ear health status were assessed in 19 children (aged 3 months to 8 years) presenting in remote western South Australia and medical interventions were recorded. Over the two-year study period, chronic suppurative OM was diagnosed at least once in 7 children (37%), acute OM with perforation in 4 children (21%), OM with effusion in 11 children (58%), while only 1 child had no ear disease. Microbiota analysis of 19 children (51 sets of left and right ear canal swabs and nasopharyngeal swabs) revealed a core group of bacterial taxa that included Corynebacterium, Alloiococcus, Staphylococcus, Haemophilus, Turicella, Streptococcus, and Pseudomonas. Within-subject microbiota similarity (between ears) was significantly greater than inter-subject similarity, regardless of differences in ear disease (p = 0.0006). Longitudinal analysis revealed changes in diagnosis to be associated with more pronounced changes in microbiota characteristics, irrespective of time interval. Ear microbiota characteristics differed significantly according to diagnosis (P (perm) = 0.0001). Diagnoses featuring inflammation with tympanic membrane perforation clustering separately to those in which the tympanic membrane was intact, and characterised by increased Proteobacteria, particularly Haemophilus influenzae, Moraxella catarrhalis, and Oligella. While nasopharyngeal microbiota differed significantly in composition to ear microbiota (P (perm) = 0.0001), inter-site similarity was significantly greater in subjects with perforated tympanic membranes, a relationship that was associated with the relative abundance of H. influenzae in ear samples (rs = − 0.71, p = 0.0003). Longitudinal changes in ear microbiology reflected changes in clinical signs and treatment. Conclusions Children attending the ear and hearing clinic in a remote Aboriginal community present with a broad spectrum of OM conditions and severities, consistent with other remote Aboriginal communities. Ear microbiota characteristics align with OM diagnosis and change with disease course. Nasopharyngeal microbiota characteristics are consistent with the contribution of acute upper respiratory infection to OM aetiology.

Moraxella-dominated pediatric nasopharyngeal microbiota associate with upper respiratory infection and sinusitis

Background Distinct bacterial upper airway microbiota structures have been described in pediatric populations, and relate to risk of respiratory viral infection and, exacerbations of asthma. We hypothesized that distinct nasopharyngeal (NP) microbiota structures exist in pediatric populations, relate to environmental exposures and modify risk of acute sinusitis or upper respiratory infection (URI) in children. Methods Bacterial 16S rRNA profiles from nasopharyngeal swabs (n = 354) collected longitudinally over a one-year period from 58 children, aged four to seven years, were analyzed and correlated with environmental variables, URI, and sinusitis outcomes. Results Variance in nasopharyngeal microbiota composition significantly related to clinical outcomes, participant characteristics and environmental exposures including dominant bacterial genus, season, daycare attendance and tobacco exposure. Four distinct nasopharyngeal microbiota structures (Cluster I-IV) were evident and differed with respect to URI and sinusitis outcomes. These clusters were characteristically either dominated by Moraxella with sparse underlying taxa (Cluster I), comprised of a non-dominated, diverse microbiota (Cluster II), dominated by Alloiococcus/Corynebacterium (Cluster III), or by Haemophilus (Cluster IV). Cluster I was associated with increased risk of URI and sinusitis (RR = 1.18, p = 0.046; RR = 1.25, p = 0.009, respectively) in the population studied. Conclusion In a pediatric population, URI and sinusitis associate with the presence of Moraxella-dominated NP microbiota.

Antibiotic Prescribing Patterns in Paediatric Primary Care in Italy: Findings from 2012–2018

Comprehensive data are needed to monitor antibiotic prescribing and inform stewardship. We aimed to evaluate the current antibiotic prescribing patterns, including treatment switching and prolongation, in the paediatric primary care setting in Italy. This database study assessed antibiotic prescriptions retrieved from Pedianet, a paediatric primary care database, from 1 January 2012 to 31 December 2018. Descriptive analyses were stratified by diagnosis class, calendar year, and children’s age. Generalized linear Poisson regression was used to assess variation in the prescriptions. In total, 505,927 antibiotic prescriptions were included. From 2012 to 2018, the number of antibiotics per child decreased significantly by 4% yearly from 0.79 in 2012 to 0.62 in 2018. Amoxicillin prescriptions decreased with increasing children’s age, while macrolides and third-generation cephalosporins had the opposite trend. Prescriptions were associated with a diagnosis of upper respiratory infection in 23% of cases, followed by pharyngitis (21%), bronchitis and bronchiolitis (12%), and acute otitis media (12%). Eight percent of treatment episodes were prolonged or switched class, mostly represented by co-amoxiclav, macrolides, and third-generation cephalosporins. Our findings report an overall decrease in antibiotic prescriptions, but pre-schoolers are still receiving more than one antibiotic yearly, and broad-spectrum antibiotics prescription rates remain the highest.

A rare case of Acute Motor and Sensory Axonal Neuropathy (AMSAN) and Immune Thrombocytopenic Purpura (ITP) related to Hemophilus influenzae

We describe a rare case presenting with both signs of acute motor and sensory axonal neuropathy (AMSAN) and immune thrombocytopenic purpura (ITP) possibly triggered by Hemophilus influenzae. Guillain-Barre is an autoimmune disorder purported to be due to molecular mimicry, often with a preceding infection, leading to myelin sheath or even axonal damage, AMSAN, in the peripheral nervous system (PNS). Rarely, there have been case reports of concurrent acute autoimmune disorders leading to a more complex presentation and additional comorbidities. A 42-year-old man presented with 2 days of progressive lower and upper extremity paresthesia’s, ataxia preceded by an upper respiratory infection. Examination showed areflexia and purpura, recent oral mucosal hemorrhage. Lab results showed severe thrombocytopenia suspicious for ITP. Over the ensuing weeks while inpatient, his condition quickly deteriorated to requiring an intubation for respiratory failure and not immediately responsive to IVIG. Recovery, both for AMSAN confirmed by EMG and ITP, was eventually achieved with time and five treatments of plasmapheresis and eventually was discharged to a rehabilitation facility. A thorough infectious workup revealed a possible trigger being Haemophilus influenzae. There have been rare occasions of concurrent GBS and ITP, but even more rare is the presence of both AMSAN and ITP which requires quick recognition and evaluation. This case highlights the need for a thorough initial history taking and a general physical exam, in addition to unique management decisions and strategies in patients with suspected GBS as there may be signs of other associated disorders that require immediate attention.

Early Diagnosis and Antibiotic Treatment Combined with Multicomponent Hemodynamic Support for Addressing a Severe Case of Lemierre’s Syndrome

A 20-year-old man was admitted to the intensive care unit for septic shock due to Lemierre’s syndrome. It is a rare syndrome that manifests as an upper respiratory infection, although systemic involvement, severe coagulopathy, and multi-organ failure can dangerously complicate the clinical picture. In this syndrome, sepsis-related neuroendocrine dysregulation and microcirculation impairment can have a rapid deleterious progression. Consequently, proper diagnosis, early source control, and appropriate antibiotics administration are mandatory to improve the prognosis. The intensive treatment is aimed at limiting organ damage through hemodynamic optimization. Remarkably, in septic shock due to Lemierre’s syndrome, hemodynamic optimization can be achieved through the synergic effect of norepinephrine, argipressin, and hydrocortisone.

Do COVID-19 Pandemic-Related Behavior Changes Affect Perioperative Respiratory Adverse Events in Children Undergoing Cardiac Interventional Catheterization?

Background: The Novel Coronavirus Disease (COVID-19) pandemic-related behavior changes could affect the perioperative respiratory adverse events in children with congenital heart disease (CHD). This study was designed to compare the incidence of perioperative respiratory adverse events (PRAEs) in children with and without upper respiratory infection (URI) undergoing the cardiac catheterization before and during COVID-19 pandemic.Methods：COVID-19 was outbreak in January 2020 in China. 260 pediatric patients scheduled for elective therapeutic cardiac catheterization were included from January 2019 to March 2021 and 154 were completed during the pandemic. Recent URI was diagnosed by the attending anesthesiologist owing to different PRAEs incidence in non-URI and URI children. The overall incidence of PRAEs (laryngospasm, bronchospasm, coughing, airway secretion, airway obstruction, and oxygen desaturation) in non-URI and URI children undergoing the elective cardiac catheterization were compared before and during the COVID-19 pandemic. Logistic regression model was fitted to identify the potential risk factors associated with PRAEs.Results: Of 564 children enrolled, 359 completed the study and was analyzed finally. URI incidence decreased substantially during the COVID-19 pandemic (14% vs. 41%, P<0.001). Meanwhile, the overall PRAEs also significantly declined no matter whether or not the child had recent URI (22.3% vs. 42.3%, P=0.001 for non-URI and 29.2% vs. 58.7%, P=0.012 for URI respectively). Post-operative agitation in non-URI children occurred less frequently during the pandemic than before (2.3% vs. 16.2%, P=0.001). Behaviors before the COVID-19 pandemic (odd ratio=2.84, 95%CI 1.76 to 4.58) and recent URI (odd ratio =1.79, 95%CI 1.09 to 2.92) were associated with the PRAEs.Conclusions: COVID-19 pandemic-related behavior changes were associated with the reduction of PRAEs in non-URI and URI children undergoing elective therapeutic cardiac catheterization.

Long-term follow-up of ibrutinib monotherapy in treatment-naive patients with Waldenstrom macroglobulinemia

Herein, we present the final report of a single-center, prospective phase II study evaluating ibrutinib 420 mg once daily in 30 treatment-naive patients with Waldenstrom macroglobulinemia (WM). The present study is registered with ClinicalTrials.Gov (NCT02604511). With a median follow-up of 50 months, the overall, major, and VGPR response rates were 100%, 87%, and 30%. The VGPR rate was numerically but not significantly lower in patients with than without CXCR4 mutations (14% vs. 44%; p = 0.09). The median time to a minor response was 0.9 months, and to a major response was 1.9 months, though were longer in those with mutated CXCR4 at 1.7 months (p = 0.07) and 7.3 months (p = 0.01). Six patients had disease progression. The median progression-free survival (PFS) was not reached, and the 4-year PFS rate was 76%. There was also a non-significant lower 4-year PFS rate in patients with than without CXCR4 mutations (59% vs. 92%; p = 0.06). The most common treatment-related adverse events were fatigue, upper respiratory infection, and hematoma. Atrial fibrillation occurred in 20% of patients. Ibrutinib monotherapy induced durable responses in treatment-naive patients with WM. CXCR4 mutations impacted VGPR attainment, time to major response, and 4-year PFS rate.

Nasopharyngeal microbiome composition associated with Streptococcus pneumoniae colonization suggests a protective role of Corynebacterium in young children

Streptococcus pneumoniae (Spn) is a leading respiratory tract pathogen that colonizes the nasopharynx (NP) through adhesion to epithelial cells and immune evasion. Spn actively interacts with other microbiota in NP but the nature of these interactions are incompletely understood. Using 16S rRNA gene sequencing, we analyzed the microbiota composition in the NP of children with or without Spn colonization. 96 children were included in the study cohort. 74 NP samples were analyzed when children were 6 months old and 85 NP samples were analyzed when children were 12 months old. We found several genera that correlated negatively or positively with Spn colonization, and some of these correlations appeared to be influenced by daycare attendance or other confounding factors such as upper respiratory infection (URI) or Moraxella colonization. Among these genera, Corynebacterium showed a consistent inverse relationship with Spn colonization with little influence by daycare attendance or other factors. We isolated Corynebacterium propinquum and C. pseudodiphtheriticum and found that both inhibited the growth of Spn serotype 22F strain in vitro.

The Antiviral and Antibacterial properties of Plectranthus amboinicus and Piper longum with the Addition to Focaccia Bread Nutritional Value and Sensory Evaluation

Focaccia is an Italian bread baked with herbs in a similar way to pizza, this can be utilized as a regular meal in daily basis, thus the bread prepared without cheese, it is considered as a good health supplement. The addition of herbs like Plectranthus amboinicus (Indian Borage) and Piper longum (long Pepper) to focaccia may increase the medicinal value. Borage is used as a medicine in treating contagious diseases like viral flu and cough through antiviral, antibacterial and antifebrile activity, likewise Piper longum acts as an antibacterial and have immunomodulation properties, piper longum is commonly known as Indian long pepper mostly used in siddha medicine to treat cough and respiratory disease. The upper respiratory infection mainly influence cough, sinusitis, sore throat, pharyngitis, also develop lung inflammation and this herb could be consumed in regular diet. The objective of this research is to analyze antiviral and antibacterial properties of Plectranthus amboinicus and Piper longum. Furthermore, to evaluate the Focaccia bread in addition with these herbs in preparation by sensory evaluation.