COMPARABLE RESULTS OF <i>HELICOBACTER PYLORI</i> ANTIMICROBIAL RESISTANCE STOOL TESTING USING NEXT GENERATION SEQUENCING VS GASTRIC BIOPSY-CULTURE WITH SUSCEPTIBILITY TESTING IN PEDIATRIC POPULATION

Background: While it is widely recognized that symptoms of eosinophilic esophagitis (EoE) differ in children versus adults, only a single case series has investigated symptoms of EoE in infants and toddlers, and few young children are included in studies of therapeutic response. Thus, the aims of the current study were 1) to characterize presentations of EoE in children < 2 years, and 2) to evaluate histologic and clinical response to treatment in this youngest pediatric age group.

Methods: This was a retrospective longitudinal study of children < 2 years diagnosed with EoE at a single tertiary center between 2016 and 2018. EoE was defined histologically by presence of > 15 eosinophils per high power field (eos/hpf) on at least one esophageal biopsy and a history suggestive of the diagnosis. Demographic characteristics, presenting symptoms, and EoE treatments were collected via chart review. Follow-up data were collected from all endoscopies after diagnosis, and histologic remission was defined as < 15 eos/hpf. Paired t-tests or Fisher exact tests for parametric data or Wilcoxin sign-rank test for non-parametric data were used to evaluate changes from baseline to follow-up in histology and clinical symptoms.

Results: Forty-two children ages 1.3 ± 0.4 years were followed for a mean of 3.6 ± 1.7 years and underwent 3.8 ± 2.3 (range 1 to 10) endoscopies under general anesthesia. Common presenting symptoms were feeding difficulties in 67% of patients (including gagging/coughing with feeding in 60% and difficulty with progression to pureed or solid foods in 43%), vomiting (57%), and coughing/wheezing (52%). Thirty-six children (86%) were male, and comorbidities included atopy (86%), reflux (74%), and a history of cow’s milk protein allergy (40%). Thirty-seven patients underwent repeat endoscopy after diagnosis, and 25/37 (68%) achieved histologic remission during the follow-up period. In addition to histologic improvement, there were significant reductions in all symptoms at follow-up compared to baseline (Figure 1). Treatment regimens were variable, and there was a significant effect of therapy type on histologic response (P = 0.004) with the best responses on combinations of diet/steroids or diet/proton pump inhibitor (PPI) and the worst response on PPIs alone (Figure 2). Of the 20 patients who underwent additional endoscopies after histologic remission, 13/20 (65%) had relapsed EoE on at least one follow-up endoscopy.

Discussion: The diagnosis of EoE should be considered in infants and toddlers presenting with feeding difficulties, vomiting, and cough or wheeze. EoE in this age group may mimic other common GI diagnoses, such as reflux or milk protein intolerance. Most patients show histologic and clinical improvements with standard therapies, but the endoscopic burden is significant and histologic response may not be maintained over time.

Background: Helicobacter pylori (H. pylori) eradication rates have declined globally making susceptibility testing increasingly important. Despite improvement in test availability of gastric biopsy-culture with susceptibility testing (gold standard) in the United States (US), culture requires an invasive procedure to obtain gastric biopsies, esophagogastroduodenoscopy (EGD), which is not devoid of potential endoscopic and anesthesia-related risks. Stool-based susceptibility testing offers a useful non-invasive option suitable for pediatric population in whom invasive diagnostic testing for the sole purpose of detecting H pylori infection is not recommended.
Methods: A total of 19 patients that underwent diagnostic endoscopic evaluation with positive resultant positive histology for H. pylori from a large pediatric tertiary care center in Boston, MA were included in the study. At our institution, we have standardized the process of gastric biopsy culture in patients with endoscopic findings of H. pylori. An antral and corpus biopsy are taken at the time of endoscopy for gastric biopsy-culture with susceptibility testing via agar dilution. Patients provided a stool sample within 2 weeks of the endoscopy, prior to the start of treatment. We evaluated agreement between the stool next generation sequencing (NGS)-based molecular testing and gastric biopsy-culture with susceptibility testing.
Results: From the 19 recruited patients, 6 (31.6%) did not have sufficient bacterial colony growth in gastric culture to run susceptibility testing. Sufficient H. pylori DNA for NGS analysis was detected in 18 (95%) patients. Thirteen patients (68.4%) had both stool NGS-based molecular test, and gastric biopsy-culture antimicrobial resistance data to compare (mean age 11.9 years [range 3-20], 6 (46%) Male, 6 (46%) Black, 4 (31%) Hispanic. Overall stool NGS-based molecular test was highly concordant with gastric biopsy-culture results for clarithromycin resistance (2 patients), and no resistance identified (11 patients). In addition, stool NGS-based molecular test was highly sensitive, providing antimicrobial resistance data in patients with poor bacterial growth in culture (5/6, 83%). All of the 5 patients were resistant to at least one antimicrobial.
Conclusion: Stool NGS-based molecular test is highly concordant with gastric biopsy-culture results, providing accurate H. pylori antimicrobial resistance data for clarithromycin non-invasively in pediatric patients.