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Letter: Resistance patterns of refractory H pylori infection in Delaware Valley referral centre: Public health research experience at the University of Pennsylvania, Philadelphia, USA

EDITORS, Helicobacter pylori-mediated gastritis/associated co-morbidities among ethnically disparate susceptible ‘at-risk’ populations have emerged as significant public health challenge warranting collaborative global clinical research efforts for successful development of cost-effective/patient-friendly/therapeutically efficacious/clinically safe treatment modalities for eventually diminishing the overwhelming trends of gastrohepatic ailments associated with refractory H pylori resistance; the meticulously conducted study by Kumar et al at the University of Pennsylvania, Philadelphia, USA provides valuable translational/public health insights regarding H pylori positivity and local resistance patterns in Delaware Valley1; the retrospective nature of study in specific patient-population pool (timeline 2009-2019) undergoing endoscopy for culture could lead to possible selection bias, and therefore future large sample size-based prospective epidemiological studies with multiethnic cohorts, including pharmacogenetic case-control genetic-association studies, are warranted to draw more definitive conclusions and eventually design cost-effective predictive biomarkers for H pylori-mediated infection(s) in genetically susceptible population subsets of varying lifestyles/dietary patterns/ geographical locations/landscapes. The major study strength was reliability of retrospective data sets with stringent assessment/review of referral hospital–based patient charts, including meticulous ascertainment of demographic profiles, clinical history, endoscopic/culture results, treatment regimens and patient follow-ups, thereby leading to convincing statistically significant outcomes with considerable study power. However, a modest sample size of N = 109 patients referred for refractory H pylori may have led to skewed data sets; interestingly, out of 109 patients, 90 were clinically confirmed for H pylori positivity (median age = 53.2 years) and relatively higher number of female patients (74%), with median 2 previous antibiotic courses for H pylori. Another study strength was the accuracy of clinical diagnosis with specific H pylori-infection status in 109 patients; the commonest endoscopic abnormality was gastric erythema, and 72.2% patients were culture positive, while 69.2% were resistant to levofloxacin, 41.5% to metronidazole and 43.3% to clarithromycin, thereby implicating the urgency to strategically develop cost-effective therapeutic modalities for efficient management of H pylori in Delaware Valley, and design future multicentric studies for stringently addressing the ever-expanding global burden of H pylori infection. The study group demonstrated strong association of number of previous antibiotics with resistance (OR = 1.74, P < .05); the investigators prescribed therapy to 77 patients based on susceptibility profiles with 37.8% being cured, 15.6% underwent endoscopic surveillance, 3.3% were followed by infectious disease and 43.3% were lost to clinical follow-up, thereby emphasizing the increasing trends of association of antibiotic resistance with refractory H pylori in American cohort. A recent study (N = 1200 subjects) evaluated eleven different therapies primarily PPI-levofloxacin-amoxicillin/PPI-bismuth-levofloxacinamoxicillin/ PPI-moxifloxacin-amoxicillin/ranitidine bismuth citratetetracycline-metronidazole/classical bismuth-containing quadruple therapy/PPI-Pylera® and PPI-rifabutin-amoxicillin, and demonstrated the effectiveness of the second-, third-, fourthand fifth-line rescue therapies: 77%, 71%, 60% and 58%, respectively, for H pylori eradication.2 Causal association of H pylori infection has been elegantly demonstrated in ethnically distinct American-Hispanic cohort(s) presenting with clinically manifested upper gastrointestinal complications and systemic metabolic syndrome (MetS).3,4 Moreover, strong/weak association of H pylori with non-alcoholic fatty liver disease (NAFLD) and/or subsequent antibiotic resistance in patients undergoing stringent treatment/follow-up/surveillance, may be attributed to interindividual variability in predictive clinical testing for risk stratification of asymptomatic/borderline/symptomatic patients. Overall, a precise dissection of the aetiology of H pylori-mediated inflammatory aberrant metabolic flux in antibiotic-resistant subsets of American patients’ cohort at the cellular, molecular and genetic levels would prove to be a boon in the rationale design of logical immunotherapeutic regimens.