Development of the Anaerobic Microbiome in the Infant Gut.

Ninety-five percent of gut microbiota are anaerobes and vary according to age and diet. Complex carbohydrates in human milk enhance the growth of Bifidobacterium and Bacteroides in the first year. Complex carbohydrates in solid foods enhance the growth of Bacteroides and Clostridium in the second year. Short-chain fatty acids produced by Akkermansia and Faecalibacterium may reduce obesity, diabetes and IBD.

The Role of Faecalibacterium, Roseburia, and Butyrate in Inflammatory Bowel Disease.

Faecalibacterium and Roseburia are major producers of butyrate in the intestine. A reduced abundance of the organisms and a concurrent reduction in butyrate levels are associated with inflammatory bowel disease.

Secretors of HBGA and Susceptibility to Norovirus and Rotavirus Diarrhea.

Histo-blood group antigen contains oligosaccharides that serve as receptors for norovirus (NoV) and rotavirus (RV). The receptors are only present on the surface of intestinal mucosal epithelial cells of secretors; therefore, secretors are susceptible to NoV and RV diarrhea and nonsecretors are resistant. The prevalence of secretors in different countries varies between 50% and 90%. Secretor rates evolved in response to environmental pressures such as infectious diseases.

Review and Commentary on the Importance of Bile Acids in the Life Cycle of Clostridioides difficile in Children and Adults.

Clostridioides difficile, a spore-forming anaerobe, resides in the intestine. The life cycle of C. difficile illustrates an interdependent relationship between bile acids, commensal microbiota, and C. difficile. Primary bile acids are critical for the germination of C. difficile spores in the small intestine, while secondary bile acids serve as a counterbalance to inhibit the growth of the organism in the colon. Many commensal bacteria especially Clostridium spp. are responsible for transforming primary bile acids into secondary bile acids. Antibiotics eliminate bacteria that convert primary bile acids into secondary bile acids and, thus, allow C. difficile to flourish and cause diarrhea. In children younger than 2 years of age, who normally only produce primary bile acids, colonization with toxin-producing C. difficile is exceedingly common. The reason for the absence of C. difficile diarrhea in the children remains unexplained.

The Response of the Gut Microbiota to Dietary Changes in the First Two Years of Life.

The infant gut microbiota undergoes significant changes in the first two years of life in response to changes in the diet. The discontinuation of the milk-based diet of the first year and the introduction of solid foods in the second year of life results in a decline in bifidobacterium, a shift from infant strains of bifidobacterium to adult strains which preferentially metabolize oligosaccharides derived from plants rather than from milk, a surge in short chain fatty acids such as acetic, propionic and butyric acid from newly acquired commensal clostridium, and the transformation of primary bile acids into secondary bile acids by a limited number of newly acquired and highly specialized Clostridium spp. By 3 years of age, diet and gut microbiota closely resemble those of adults. Gut bacteria required for the production of SCFAs and secondary BAs are potential targets for the intervention of microbiome-related diseases.

The milk-based diet of infancy and the gut microbiome.

The composition and the diversity of the gut microbiome play a major role in the health and well-being of humans beginning at birth. The impact of the diet on the structure and the function of the gut microbiome is evident by the changes in the gut microbiome concurrent with the transition from human milk to solid food. Complex oligosaccharides contained in milk are essential nutrients for commensal microbes in the infant gut. The most important commensal bacterium in the infant gut, bifidobacterium, requires α1, 2 fucosylated oligosaccharides for growth. Because not all humans are able to secrete α1, 2 fucosylated oligosaccharides into milk, the gut microbiome of infants and bifidobacteria, in particular, vary considerably between 'secretors' and 'non-secretors'. A paucity of α1, 2 fucosylated oligosaccharides and bifidobacteria in the gut of infants may be associated with poor health.

Interactions of bile acids and the gut microbiota: learning from the differences in Clostridium difficile infection between children and adults.

Bile acids and microbiota differ significantly in the gut of children and adults. In the first 3 yr of life, intestinal bile consists mostly of two primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA); however, in adults, primary bile acids are transformed into the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid. This difference has a major impact on the gut microbiome, especially on anaerobic spore-forming bacteria. CA augments germination of spores in the terminal ileum. On the other hand, DCA curtails the number of germinated anaerobes entering the cecum from the terminal ileum. The control mechanism that exists in the adult cecum is absent in the young child and results in unrestrained proliferation of anaerobes, such as Clostridium difficile, in the cecum. A similar situation may develop during antibiotic therapy when an antibiotic eradicates the anaerobic population capable of converting primary bile acids into secondary bile acids.

Infections Associated With Streptococcus Constellatus in Children.

Streptococcus constellatus is a viridans Streptococcus belonging to the Anginosus group. It was associated with abscesses in 37 children, 80% of whom had acute appendicitis with perforation and abscess formation in 50%. None of the children was <3 years of age.

The ubiquity of asymptomatic respiratory viral infections in the tonsils and adenoids of children and their impact on airway obstruction.

BACKGROUND: Airway obstruction due to enlargement of tonsils and adenoids is a common pediatric problem resulting in sleep disordered breathing. The cause for the relatively abnormal growth of tonsils and adenoids is poorly understood. METHODS: Non-acutely ill children undergoing tonsillectomy and adenoidectomy (T&A) for various reasons were enrolled prospectively in a study to determine the frequency of asymptomatic respiratory viral infections in each lymphoid tissue and to relate the number and types of virus to the degree of airway obstruction. Molecular techniques were used to detect 9 respiratory viruses while Brodsky scores and measurements of percentages airway obstruction were used to estimate the degree of airway compromise due to the tonsil and adenoid, respectively. RESULTS: Viruses were detected in 70.9% of tonsils and 94.7% of adenoids, p < 0.001. Adenovirus was the most common virus detected at 71.1%. Adenoids had an average of 2.4 viruses compared to 0.92 for tonsils, p < 0.001. Higher Brodsky scores were only associated with EBV in tonsils, p = 0.03, while greater percentages of airway obstruction in the adenoids were associated with adenovirus, EBV, corona virus, parainfluenza virus and rhinovirus, p ≤ 0.005. CONCLUSIONS: Asymptomatic viral infections are common and directly related to the degree of airway obstruction significantly more often in adenoids than tonsils.

Infections Associated with Streptococcus intermedius in Children.

Streptococcus intermedius is a viridans Streptococcus belonging to the Anginosus group. In the past 7 years, it has been associated with abscesses in 48 children, 40% of whom had complicated and/or life-threatening illness. It was the sole pathogen in 35 cases. Seventy-five percent of the infections occurred in winter and spring. None occurred in infants younger than 1 year.

Trimethoprim-Sulfamethoxazole Therapy Reduces Failure and Recurrence in Methicillin-Resistant Staphylococcus aureus Skin Abscesses after Surgical Drainage.

OBJECTIVE: To determine whether a 3-day vs 10-day course of antibiotics after surgical drainage of skin abscesses is associated with different failure and recurrence rates. STUDY DESIGN: Patients age 3 months to 17 years seeking care at a pediatric emergency department with an uncomplicated skin abscess that required surgical drainage were randomized to receive 3 or 10 days of oral trimethoprim-sulfamethoxazole therapy. Patients were evaluated 10-14 days later to assess clinical outcome. Patients were followed for 6 months to determine the cumulative rate of recurrent skin infections. RESULTS: Among the 249 patients who were enrolled, 87% of wound cultures grew Staphylococcus aureus (S aureus) (55% methicillin-resistant S aureus [MRSA], 32% methicillin-sensitive S aureus), 11% other organisms, and 2% no growth. Thirteen patients experienced treatment failure. Among all patients, no significant difference in failure rates between the 3- and 10-day treatment groups was found. After we stratified patients by the infecting organism, only patients with MRSA infection were more likely to experience treatment failure in the 3-day group than the 10-day group (P = .03, rate difference 10.1%, 95% CI 2.1%-18.2%) Recurrent infection within 1 month of surgical drainage was more likely in patients infected with MRSA who received 3 days of antibiotics. (P = .046, rate difference 10.3%, 95% CI 0.8%-19.9%). CONCLUSION: Patients with MRSA skin abscesses are more likely to experience treatment failure and recurrent skin infection if given 3 rather than 10 days of trimethoprim-sulfamethoxazole after surgical drainage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02024867.

Trends in Oral Antibiotic, Proton Pump Inhibitor, and Histamine 2 Receptor Blocker Prescription Patterns for Children Compared With Adults: Implications for Clostridium difficile Infection in the Community.

The use of antibiotics, proton pump inhibitor (PPI), and histamine 2 receptor blocker (H2B) was compared between children and adults in the community from 2005 through 2011. Antibiotic prescription rates remained stable for children, but increased significantly for adults, P = .03. PPI prescription rates increased for children, P = .02 and for adults, P = .009. H2B prescription rates increased for children, P = .03, but not for adults. Antibiotic prescription rates were significantly higher in children than adults in all 7 years, P < .0001. In contrast, PPI prescription rates were significantly higher in adults than children in all 7 years, P < .0001. H2B prescription rates were significantly higher in adults than children 1 to 18 years old P < .0001; however, H2B prescription rates were highest in children <1 year old, P = .0001. The high use of oral antibiotics, PPI, and H2B among outpatients may be a contributing factor to the rise of Clostridium difficile infection in the community.

Importance of asymptomatic shedding of Clostridium difficile in environmental contamination of a neonatal intensive care unit.

A survey of C. difficle in a neonatal intensive care unit (NICU) was conducted. Approximately 25% of infants in the NICU were colonized with Clostridium difficle. Environmental surface cultures were obtained from the NICU and compared with cultures taken from infant, adolescent, and hematology/oncology units. From 150 surface cultures, C difficle was recovered exclusively from the NICU. Of the 16 different types of surfaces cultured, diaper scales and the surrounding area were contaminated most often at 50%.

Neurologic complications of 2009 influenza-a H1N1 infection in children.

Little is known about the neurologic complications of the 2009 Influenza-A H1N1 epidemic in children. We present a retrospective analysis of children evaluated at a tertiary children's hospital who tested positive for H1N1 with neurologic complications. A total of 164 children tested positive for H1N1. Thirty-one of these patients (19%) were evaluated and discharged from the emergency department. Thirty-nine (24%) were treated in the intensive care unit, the remaining 94 (57%) were treated in medical in-patient units. Six subjects died (3.7%). Neurologic complications identified included headache, encephalitis, polyneuropathy, seizures, and malignant hyperthermia. The rate of neurologic complications in this cohort of patients who tested positive for H1N1 was 19%. The incidence of serious neurologic complications was 3%, with another 3% of patients who experienced rapid clinical deterioration and subsequently died. Our observation of neurologic complications associated with 2009 influenza-A H1N1 epidemic suggests the need for clinical vigilance during future influenza epidemics.

Impact of management and bacterial genomics on outcomes of Staphylococcus aureus bacteremia in children.

Children with Staphylococcus aureus bacteremia (SAB) generally presented with nonsevere signs and symptoms in sharp contrast to reports of adults with SAB. Despite incomplete adherence to current management guidelines, children with SAB did not experience mortality or relapse. Molecular characteristics of strains responsible for SAB in children were not significantly different than those described in adults. Improved outcomes in pediatric SAB compared with adults may most likely be attributed to less severe comorbidities in children.

Azithromycin-induced agitation and choreoathetosis.

We report a child who developed agitation and choreoathetoid movements with azithromycin therapy on 2 separate occasions. In both instances, the symptoms resolved when the antibiotic was discontinued. By means of the Naranjo adverse drug reaction probability scale, we classified this event as a probable adverse drug reaction (score of 6 points). To our knowledge, this is the first published case of azithromycin-induced agitation with choreoathetosis. Because this is a widely used medication for many common infectious conditions, including otitis media and pneumonia, this potential serious adverse reaction should be considered.

Genomic comparisons of USA300 Staphylococcus aureus colonizating the nose and rectum of children with skin abscesses.

USA300 Staphylococcus aureus is responsible for the current outbreak of skin abscesses in the United States. Unlike other USA types, USA300 colonizes the rectum at rates higher than the nose. The reason for the difference in colonization site preference may be related to specific adherence or attachment factors contained in the genome of these strains. Additional knowledge in this field may help design novel prophylactic and therapeutic strategies to combat staphylococcal infections. Strains of USA300 MSSA and MRSA colonizing the nose and/or rectum from children with staphylococcal skin abscesses were compared by whole genome array technology to identify bacterial genetic determinants associated with site-specific colonization. Strains isolated from different colonization sites were indistinguishable by genomic content. Site-specific colonization traits were not detected in the colonizing bacteria by this array. Either host characteristics associated with staphylococcal carriage or under represented bacterial genomic constructions need to be examined to determine the etiology of this site-specific colonization.