Helicobacter pylori Antimicrobial Resistance and the Role of Next-Generation Sequencing.

Helicobacter pylori infection affects over half of the world's population and is a global health concern because it contributes to chronic and fatal gastrointestinal disorders, including peptic ulcer disease and gastric cancer. The escalating prevalence of antibiotic-resistant strains of H pylori necessitates a change in management. The conventional strategy of empiric-based treatments is becoming increasingly ineffective in both adult and pediatric populations; rates of eradication to common first-line regimens remain suboptimal and continue to decline. Culture-based susceptibility testing for H pylori has been underutilized and challenging to incorporate into practice. Next-generation sequencing (NGS), which can identify the genetic biomarkers that predict antimicrobial resistance and susceptibility patterns, offers a promising alternative. NGS may enable clinicians to tailor individual treatment regimens and contribute to epidemiologic surveillance across populations. As NGS technology advances and becomes more accessible, its integration into routine clinical practice holds the potential to transform H pylori management strategies and improve patient outcomes. This article reviews the literature describing antimicrobial resistance patterns in adult and pediatric practice in the United States and provides practical guidance on the current role of NGS in the management of H pylori.

Safety and Durability of Accelerated Infliximab Dosing Strategies in Pediatric IBD: A Single Center, Retrospective Study.

OBJECTIVES: Infliximab (IFX) is commonly used to treat children with inflammatory bowel disease (IBD). We previously reported that patients with extensive disease started on IFX at a dose of 10 mg/kg had greater treatment durability at year one. The aim of this follow-up study is to assess the long-term safety and durability of this dosing strategy in pediatric IBD. METHODS: We performed a retrospective single-center study of pediatric IBD patients started on IFX over a 10-year period. RESULTS: Two hundred ninety-one patients were included (mean age = 12.61, 38% female) with a follow-up range of 0.1-9.7 years from IFX induction. One hundred fifty-five (53%) were started at a dose of 10 mg/kg. Only 35 patients (12%) discontinued IFX. The median duration of treatment was 2.9 years. Patients with ulcerative colitis ( P ≤ 0.01) and patients with extensive disease ( P = 0.01) had lower durability, despite a higher starting dose of IFX ( P = 0.03). Adverse events (AEs) were observed to occur at a rate of 234 per 1000 patient-years. Patients with a higher serum IFX trough level (≥20 µg/mL) had a higher rate of AEs ( P = 0.01). Use of combination therapy had no impact on risk of AEs ( P = 0.78). CONCLUSIONS: We observed an excellent IFX treatment durability, with only 12% of patients discontinuing therapy over the observed timeframe. The overall rate of AEs was low, the majority being infusion reactions and dermatologic conditions. Higher IFX dose and serum trough level> 20 µg/mL were associated with higher risk of AEs, the majority being mild and not resulting in cessation of therapy.

Durability of Infliximab Is Associated With Disease Extent in Children With Inflammatory Bowel Disease.

OBJECTIVES: The aim of the study was to evaluate infliximab (IFX) dosing and treatment durability relative to luminal disease burden in patients with inflammatory bowel disease. METHODS: Records from 98 pediatric patients treated with IFX between 2012 and 2014 were reviewed. Disease extent was classified as "limited," "moderate," or "extensive" based on cumulative assessment of mucosal involvement. Patients started taking standard 5 mg/kg dosing were compared with those initiated taking 10 mg/kg with regard to treatment durability. RESULTS: Overall, 26.4%, 58.3%, and 70% with limited, moderate, or extensive disease, respectively, started taking a standard IFX dose of 5 mg/kg required therapy escalation. Patients with moderate and extensive disease, started taking the 5 mg/kg per dose, showed statistically significant shorter times to escalation than those with limited disease. The percentage of patients remaining on their initial 5 mg/kg per dose at 12 months was 80.1%, 56.9%, and 40.0% for limited, moderate, and extensive disease, respectively. Among patients started taking 10 mg/kg, 100% remained on this dose. All the patients with limited disease who required dose escalation continued on the higher dose at the time of analysis; however, among those with the most extensive disease, 43% failed escalation because of nonresponse or infusion reaction. CONCLUSIONS: Patients with extensive disease started taking 5 mg/kg of IFX were more likely to require dose escalation compared to those with limited or moderate disease. All of the patients with moderate and extensive disease started taking 10 mg/kg of IFX remained on this dose. These results suggest that patients with more extensive disease may benefit from higher initial IFX dosing as it relates to durability of the treatment.