Antibiotic resistance, heteroresistance, and eradication success of Helicobacter pylori infection in children.

BACKGROUND: Antibiotic resistance is a well-known factor of Helicobacter pylori eradication failure. Heteroresistance indicates the coexistence of resistant and susceptible strains and might lead to underestimating antimicrobial resistance. This study aims to evaluate the susceptibility profile, the frequency of heteroresistance of H. pylori strains, and their effect on eradication success in a pediatric population. MATERIALS AND METHODS: Children aged 2-17 years who underwent an upper gastrointestinal endoscopy from 2011 to 2019 with positive H. pylori status were included. Susceptibility was measured by disk diffusion and E-test. The difference in susceptibility profiles between isolates from the antrum and the corpus was used to detect heteroresistance. For those who received eradication treatment, we evaluated eradication rate and factors affecting treatment success. RESULTS: Inclusion criteria were met by 565 children. Strains susceptible to all antibiotics were detected in 64.2%. Primary resistance rates for clarithromycin (CLA), metronidazole (MET), levofloxacin (LEV), tetracyclin (TET), and amoxicillin (AMO) were 11%, 22.9%, 6.9%, 0.4%, and 0% and secondary resistance rates were 20.4%, 29.4%, 9.3%, 0%, and 0%. Heteroresistance was present in untreated children in 2%, 7.1%, 0.7%, 0.7%, and 0% for CLA, MET, LEV, TET, and AMO. First-line eradication rates were 78.5% in intention-to-treat (ITT), 88.3% in full-analysis-set (FAS), and 94.1% in per-protocol (PP). Factors affecting eradication success were the duration of treatment when the triple-tailored treatment was used, the number of daily doses of amoxicillin administered, and the patient's adherence to treatment. CONCLUSIONS: This study shows the presence of relatively low primary resistance rates for H. pylori isolates but demonstrates the presence of heteroresistance in our population. Routine biopsies from the antrum and corpus must be considered for susceptibility testing to allow tailored treatments and increase eradication rates. Treatment success is affected by treatment choice, correct dosing of medications, and adherence. All these factors should be considered when evaluating the efficacy of an eradication regimen.

Efficacy and safety of bismuth-based quadruple therapy for Helicobacter pylori eradication in children.

OBJECTIVES: To evaluate the efficacy and safety of a 10-day quadruple therapy containing colloidal bismuth sub-citrate (CBS), esomeprazole (ESO), amoxicillin (AMO), and metronidazole (MET) for Helicobacter pylori (H. pylori) eradication in children. METHODS: Monocentric, open-label, prospective, single-arm clinical trial in children aged 6-17 years with H. pylori infection. The study was carried out on consecutive patients with upper gastrointestinal symptoms and H. pylori infection confirmed by histology and culture of gastric biopsies. The outcome was evaluated using a 13 C-urea breath test 8-10 weeks post-therapy. Adverse events and compliance were evaluated by daily journal and pill counting. RESULTS: A total of 36 children fulfilling the inclusion criteria were enrolled. Eight (22.2%) of them had a prior H. pylori eradication treatment. Thirteen (36.1%) patients were infected by a strain resistant to MET and 8 (22.2%) by a strain resistant to both MET and Clarithromycin (CLA). In the intention-to-treat population (ITT), eradication was achieved in 35/36 patients (95%CI: 85%-99%). Twenty-three children reported at least one adverse event (63.8%), mostly mild (nausea, vomiting, abdominal pain, diarrhea, dark stool, metallic taste, headache, and rash). The compliance rate was high, with 30 (83.3%) patients taking >90% of the treatment. CONCLUSION: 10-day quadruple therapy containing CBS, ESO, AMO, and MET for H. pylori eradication in children is a safe and very effective solution, especially for previously treated patients and those infected with double resistant strains.

Management of esophageal motility disorders in children : a review.

Diagnostic criteria for esophageal motor disorders have recently been updated with the advent of high-resolution manometry that gives a precise mapping of peristaltic abnormalities and an indirect view of bolus transit problems. Achalasia, the best-defined motor disorder, is now divided in subsets of manometric phenotypes that predict outcome of treatment and guide our therapeutic approach. Pharmacological therapy using smooth muscle relaxants for spastic esophageal disorders remains poorly effective and used only as a bridge to more effective therapies : endoscopic balloon dilation and surgical myotomy are both effective therapies in achalasia, myotomy being considered as the preferred approach in children because it is aimed to be definitive, while dilations usually have to be repeated. Recently, peroral endoscopic myotomy was introduced as an alternative to surgical myotomy for achalasia, and was rapidly adopted in tertiary referral centers. Showing excellent short-term results, this technique might be also proposed for other esophageal spastic disorders. Gastroesophageal reflux disease and eosinophilic esophagitis, two prevalent diseases in children that may be associated with hypotensive and hypertensive peristaltic abnormalities, have to be searched because specific effective therapies exist for these diseases that may cure the motility disorders.

Interest of Anorectal Manometry During Long-term Follow-up of Patients Operated on for Hirschsprung's Disease.

BACKGROUND/AIMS: Although many advances in the management of Hirschsprung's disease have recently been achieved, postoperative outcomes of these patients remain difficult in a non-negligible number of cases. Therefore, this study aims at investigating characteristics of anorectal manometry and its relationship with postoperative outcomes during long-term follow-up in Hirschsprung patients. METHODS: Patients over 4 years of age operated on for Hirschsprung's disease were interviewed to complete detailed questionnaires on bowel function. The patients who consented to undergo an anorectal manometry during follow-up were enrolled in this study. We investigated their clinical characteristics, manometric findings, and their postoperative bowel function. RESULTS: Nineteen patients out of 53 patients (35.8%) were enrolled, 68.4% who were male. Mean age of patients at manometry was 11.3 ± 6.3 years. Twelve out of 19 patients (63.2%) were incontinent. The mean anal resting pressures of incontinent patients were significantly lower than continent patients (47 ± 12 mmHg versus 63 ± 11 mmHg, P < 0.05, t test). Due to neurological impairment, only 11 patients (57.9%) were able to perform a complete manometry. A dyssynergic defecation was found in 4 patients during strain tests. Maximum tolerated volume of the incontinent patients was significantly lower than that of the continent patients (97 ± 67 mL versus 181 ± 74 mL, P < 0.05, t test). CONCLUSION: Anorectal manometry is an objective method providing useful information that could guide a more adapted management in patients with defecation disorders after Hirschsprung's disease operation.

Long-Term Outcomes and Quality of Life in Patients after Soave Pull-Through Operation for Hirschsprung's Disease: An Observational Retrospective Study.

INTRODUCTION: Patients after pull-through operation for Hirschsprung's disease (HD) are at high risk of defecation disorders. This study aimed at investigating their long-term outcomes and quality of life (QoL) in comparison with controls. PATIENTS AND METHODS: Patients older than 5 years operated on for HD were interviewed to complete detailed questionnaires on bowel function. Patients without neurologic impairment were enrolled in a QoL survey to compare with controls matched for sex and age and selected randomly from the general population using sampling set in a ratio of four controls to one case of HD. RESULTS: In total, 53 operated patients were enrolled. Mean age of the patients was 16 ± 8 years, with 68% boys. Rectosigmoid aganglionosis was the most seen form of HD in 38 (72%) cases. Open Soave was performed in 40 (75.5%) cases, and minimally invasive surgery Soave (MIS Soave) in 13 (24.5%) cases. At investigation, prevalence of fecal incontinence and constipation were 22.6 and 13.2%, respectively. Regarding QoL survey, 45 patients and 180 controls were enrolled, excluding 8 patients with neurologic impairment. Thirty-seven (82.2%) patients were classified as having a good QoL (score ≥ 9 points); whereas six had a fair QoL (5-8 points) and two had a poor QoL (< 5 points). QoL score in the cases and the controls were 10.2 ± 2.5 and 11.9 ± 0.4 points, respectively. Long aganglionosis form of HD was significantly associated with a low QoL (score < 8 points), adjusted odds ratio = 9, 95% confidence interval [1.3; 64.1] (p < 0.05). In subscales analyses, the prevalence of each dimension including fecal continence, school absenteeism, unhappiness or anxiety, food restriction, and peer rejection was significantly higher in operated patients than in controls (p <0.001). CONCLUSION: Although the QoL of patients operated on for HD in general was with good outcomes, fecal incontinence and constipation still are problematic issues and challenges in a high percentage of patients. Therefore, a long-term and multidisciplinary follow-up is essentially required for these patients.

Eradication rate of Helicobacter Pylori infection is directly influenced by adherence to therapy in children.

BACKGROUND: Current commonly accepted strategies to eradicate Helicobacter pylori in children are a 10-day sequential treatment or a triple therapy for 7-14 days. To avoid further expensive and possibly risky investigations as well as induction of secondary antimicrobial resistance, a success rate of elimination strategies over 90% in a per-protocol analysis is the target goal but rates observed in clinical trials are lower. Antimicrobial resistance is a well-recognized risk factor for treatment failure; therefore, only a treatment tailored to susceptibility testing should be recommended. Adherence to therapy is also a risk factor for treatment failure but that has been poorly studied. The purpose of this study was to evaluate the influence of adherence to therapy on the elimination rates obtained with different treatment regimens. METHODS: Cohort study analysis of children, aged 2-17 years, treated for Helicobacter pylori infection between October 2011 and December 2013. As a routine clinical practice, children infected with a strain susceptible to clarithromycin and to metronidazole received either a sequential regimen or a 10-day triple therapy while children infected with a strain resistant to clarithromycin or metronidazole received a 10-day triple regimen tailored to antimicrobial susceptibility. The eradication rate was assessed by a negative 13 C-urea breath test performed at least 8 weeks after the end of the treatment and adherence evaluated using a diary. RESULTS: One hundred forty-five children (67 girls/78 boys, median age 9.7 years) fulfilled the inclusion criteria, 118 being infected with a strain susceptible to both clarithromycin and metronidazole, 10 with a clarithromycin resistant, and 17 with a metronidazole resistant strain. A sequential regimen was prescribed in 44, a triple therapy containing clarithromycin in 84 and containing metronidazole in 17. Follow-up data were available for 130/145 and clearance of the infection observed in 105 of them. A concordance of more than 90% between the prescribed and the ingested drugs was observed in 109 children, between 50 and 90% in eight, less than 50% in 11 while these data were unknown for 2/130. A successful eradication was achieved for 89.9% of patients that received at least 90% of the prescribed drugs, whereas the eradication rate for nonadherent patients was 36.6%. Adherence above 90% was significantly higher in the absence of chronic concomitant disease, in the absence of adverse event and results in a significantly higher eradication rate. With the proposed strategy and an adherence higher than 90%, eradication was obtained in 98/109 children, the rate being only significantly superior to 90% with the sequential regimen. CONCLUSION: Adherence to therapy is a very important factor for the outcome and has to be assessed when evaluating the outcome of an H. pylori eradication regimen in order to understand the reasons of treatment failure. As we treated only after evaluation of the resistance of the H. Pylori strains, we were expecting to reach the given objective of 90% successful treatment. Children with adherence to treatment above 90% had a successful outcome of 89,9%, whereas nonadherent had a successful outcome of 36,8%. This is the first time that adherence has been assessed accurately.

Education and Hypnosis for Treatment of Functional Gastrointestinal Disorders (FGIDs) in Pediatrics.

FGIDs in children and adolescents (ROME III classification) have a significant impact on the daily functioning and quality of life. Often it is the pain that is one of the main contributors to the burden of functional dyspepsia, functional abdominal pain (syndrome), and irritable bowel syndrome. Current knowledge confirms that a number of integrated networks at cortical and subcortical sites are responsible for the experience of pain. From the work of Mayer and Tillisch (2011), mainly based on structural and functional magnetic resonance imaging and positron emission tomography, it has become clear that abdominal pain syndromes are disorders of the bi-directional mind-brain-gut interactions. In this multi-factorial bio-psycho-social model we recognize the importance of neurobiological processes in the mind-brain-gut interactions, leading to alterations in motility, sensation, and immune functions. Medical treatment often offers little or no relief. Until now pharmaceutical research has not succeeded in developing safe new drugs with an effect on the brain-gut axis. More recent published research shows the rationale for the use of medical hypnosis in FGID. In this article the author will illustrate her specific approach in a pediatric gastroenterology clinic with children and adolescents with FGIDs. Being a pediatric gastroenterologist, the author emphasizes the importance of a clear diagnosis, explains the rationale for educating the patient and his or her parents on the multi-factorial bio-psycho-social model and the concepts of chronic pain, discusses the specific settings and pitfalls for hypnosis treatment in children, and last but not least, provides some examples of hypnotic sessions used with FGIDs.

Probióticos e prebióticos na prevenção e no tratamento de doenças em lactentes e crianças / Probiotics and prebiotics in prevention and treatment of diseases in infants and children

OBJETIVO: Avaliar o impacto do uso de probióticos e prebióticos na saúde das crianças. FONTES DOS DADOS: Foram pesquisados os bancos de dados MEDLINE e LILACS, selecionando-se artigos relevantes em inglês e francês. SÍNTESE DOS DADOS: O leite humano é rico em oligossacarídeos prebióticos e pode conter probióticos. Não existem dados sugerindo que a adição de probióticos a fórmulas para lactentes possa ser prejudicial, mas as evidências de sua eficácia são insuficientes para que seja recomendada. Visto que dados sugerem que a adição de oligossacarídeos prebióticos específicos pode reduzir infecções e atopia em lactentes saudáveis, sua adição parece razoável. Os benefícios a longo prazo dos pro e prebióticos para o sistema imunológico em desenvolvimento ainda precisam ser comprovados. Probióticos selecionados reduzem a duração da diarreia infecciosa em 1 dia, mas faltam evidências quanto à prevenção, exceto na diarreia associada a antibióticos. Alguns probióticos específicos previnem a enterocolite necrosante, e outros micro-organismos podem ser benéficos nos casos de gastrite por Helicobacter pylori e de cólica do lactente. Não há evidências suficientes para recomendar o uso de probióticos na prevenção e no tratamento da dermatite atópica. A utilização de probióticos nos casos de constipação, síndrome do intestino irritável, doença inflamatória intestinal e infecções extraintestinais requer mais estudos. CONCLUSÕES: A duração da administração, a dosagem microbiana e as espécies utilizadas necessitam de maior validação, tanto para probióticos quanto para prebióticos. Alegações de saúde injustificadas são uma grande ameaça ao conceito de pro e prebióticos.

OBJECTIVE: To evaluate the impact of probiotics and prebiotics on the health of children. SOURCES: MEDLINE and LILACS were searched for relevant English and French-language articles. SUMMARY OF THE FINDINGS: Human milk is rich in prebiotic oligosaccharides and may contain some probiotics. No data suggest that addition of probiotics to infant formula may be harmful, but evidence of its efficacy is insufficient for its recommendation. Since data suggest that addition of specific prebiotic oligosaccharides may reduce infections and atopy in healthy infants, their addition to infant formula seems reasonable. Long-term health benefits of pro- and prebiotics on the developing immune system remain to be proven. Selected probiotics reduce the duration of infectious diarrhea by 1 day, but evidence in prevention is lacking, except in antibiotic-associated diarrhea. Some specific probiotics prevent necrotizing enterocolitis, and other microorganisms may be beneficial in Helicobacter pylori gastritis and in infantile colic. Evidence is insufficient to recommend probiotics in prevention and treatment of atopic dermatitis. The use of probiotics in constipation, irritable bowel syndrome, inflammatory bowel disease, and extra-intestinal infections requires more studies. CONCLUSIONS: Duration of administration, microbial dosage, and species used need further validation for both pro- and prebiotics. Unjustified health claims are a major threat for the pro- and prebiotic concept.

Probiotics and prebiotics in prevention and treatment of diseases in infants and children.

OBJECTIVE: To evaluate the impact of probiotics and prebiotics on the health of children. SOURCES: MEDLINE and LILACS were searched for relevant English and French-language articles. SUMMARY OF THE FINDINGS: Human milk is rich in prebiotic oligosaccharides and may contain some probiotics. No data suggest that addition of probiotics to infant formula may be harmful, but evidence of its efficacy is insufficient for its recommendation. Since data suggest that addition of specific prebiotic oligosaccharides may reduce infections and atopy in healthy infants, their addition to infant formula seems reasonable. Long-term health benefits of pro- and prebiotics on the developing immune system remain to be proven. Selected probiotics reduce the duration of infectious diarrhea by 1 day, but evidence in prevention is lacking, except in antibiotic-associated diarrhea. Some specific probiotics prevent necrotizing enterocolitis, and other microorganisms may be beneficial in Helicobacter pylori gastritis and in infantile colic. Evidence is insufficient to recommend probiotics in prevention and treatment of atopic dermatitis. The use of probiotics in constipation, irritable bowel syndrome, inflammatory bowel disease, and extra-intestinal infections requires more studies. CONCLUSIONS: Duration of administration, microbial dosage, and species used need further validation for both pro- and prebiotics. Unjustified health claims are a major threat for the pro- and prebiotic concept.

Intestinal microbiota and health in childhood.

Western medicine has only recently discovered that the intestinal microbiota is a major determinant of the well-being of the host. Although it would be oversimplifying to limit the benefits of breastfeeding compared to cow milk based infant formula to differences in gastrointestinal flora, the impact of the latter has been demonstrated beyond doubt. As a consequence, gastro intestinal flora manipulation with pre- and probiotics added to infant formula or food (mainly milk based products) and/or with food supplements have become a priority area of high quality research. The composition of intestinal microbiota can be manipulated with "biotics": antibiotics, prebiotics and probiotics. Commercialised pre- and probiotic products differ in composition and dose. Major threats to the concept of developing a major role for intestinal microbiota manipulation on health are the commercialisation of products claiming health benefits that have not been validated. Legislation of food supplements and medication differs substantially and allows commercialisation of poor quality food supplements, what will result in negative experiences. Medicinal products can only be advertised for which there is scientific proof of benefit that has been demonstrated with "the same product with the same dose in the same indication". Specificity of prebiotics and probiotics strains and product specificity are of importance, although high quality evidence for this assertion is missing. Dose-efficacy studies are urgently needed. Probiotics are "generally regarded as safe", but side effects such as septicemia and fungemia have sometimes been reported in high-risk situations.