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.

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 high rate of adverse drug events in children receiving prolonged outpatient parenteral antibiotic therapy for osteomyelitis.

Forty-five children treated with 82 courses of 15 different antibiotics over 344 weeks during outpatient parenteral antibiotic therapy were evaluated for adverse drug events (ADE). Fifty-one percent of the courses had an associated ADE and 32.5% of the antibiotic courses were discontinued because of ADE. Vancomycin had the highest ADE rate at 85.7% and ceftriaxone had the highest ADE-related discontinuation rate at 66.7%. Cefazolin had the lowest rate of ADE and ADE-related discontinuation rates at 0% for both.

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.

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.

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%.

Interference of nontypeable Haemophilus influenzae and Moraxella catarrhalis by Streptococcus oralis in adenoid organ culture: a possible strategy for the treatment of the otitis-prone child.

The role of viridans group streptococci (Streptococcus oralis) in the prevention of colonization with nontypeable Haemophilus influenzae and Moraxella catarrhalis was investigated in an adenoid organ culture system. The adenoids from 100 patients who were undergoing adenoidectomy for either hypertrophy or recurrent otitis media were used. Streptococcus oralis Parker uniformly inhibited colonization with nontypeable H. influenzae or M. catarrhalis over a 24-hour period of incubation in adenoid organ culture. Streptococcus oralis Booth, a noninhibitory strain, did not significantly reduce colonization with nontypeable H. influenzae and M. catarrhalis. The results indicate that some strains of S. oralis may inhibit colonization with potential pathogens in the nasopharynx. It is therefore possible that colonization with inhibitory strains of viridans streptococci may be used in the nasopharynx as a relatively safe and inexpensive approach to prevention of recurrent otitis media in some children.

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.

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.

Acute disseminated encephalomyelitis in children.

OBJECTIVE: To describe the epidemiologic, clinical, neuroimaging, and laboratory features; treatment; and outcome in a cohort of children with acute disseminated encephalomyelitis (ADEM). METHODS: A 6-year retrospective chart review of children with the diagnosis of ADEM was conducted. RESULTS: Eighteen cases were identified. Sixteen patients (88%) presented in either winter or spring. Thirteen children (72%) had a recent upper respiratory tract illness. Patients presented most often with motor deficits (77%) and secondly with altered consciousness (45%). Spinal fluid abnormalities occurred in 70%. Despite rigorous microbiologic testing, a definite microbiologic diagnosis was established only in 1 child with Epstein-Barr virus disease and probable or possible diagnoses in 3 children with Bartonella henselae, Mycoplasma pneumoniae, or rotavirus disease. Brain magnetic resonance imaging identified lesions in the cerebral cortex in 80%, in subcortical white matter in 93%, in periventricular white matter in 60%, in deep gray matter in 47%, and in brainstem in 47% of patients. Eleven patients (61%) were treated with corticosteroids, and 2 were treated with intravenous immunoglobulins. All patients survived. Three patients (17%) had long-term neurologic sequelae. CONCLUSIONS: Epidemiologic evidence from this study suggests an infectious cause for ADEM. The agent is most likely a difficult-to-diagnose winter/spring respiratory virus. Magnetic resonance imaging was the neuroimaging study of choice for establishing the diagnosis and for following the course of the disease. Prognosis for survival and outcome was excellent. Recurrent episodes of ADEM must be differentiated from multiple sclerosis.

Lymphocyte proliferative response to P6 of Haemophilus influenzae is associated with relative protection from exacerbations of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by periodic exacerbations, some of which are caused by nontypeable Haemophilus influenzae (NTHI). P6 is an outer membrane lipoprotein that is highly conserved among strains of NTHI. We hypothesized that lymphocytes from patients with COPD who have exacerbations due to NTHI have a decreased ability to recognize P6. The in vitro lymphocyte proliferative response to P6 in 36 patients with COPD and 12 healthy control subjects was studied. Ten patients who had exacerbations due to NTHI in the previous 12 months showed statistically significant lower proliferation to P6 (stimulation index, log transformed mean +/- standard error 0.82 +/- 0.17) compared with 26 patients who had no exacerbations due to NTHI in the previous 12 months (1.42 +/- 0.13) and to 12 healthy control subjects (1.61 +/- 0.16). These three groups had no significant difference in the lymphocyte proliferative response to tetanus toxoid. There was no difference in serum antibody levels to P6 in the two groups with COPD. These results indicate that decreased proliferation of T cells to P6 is associated with exacerbations of COPD and suggest that the ability of T cells to recognize P6 is associated with relative protection from exacerbations due to NTHI.