Helicobacter pylori (H. pylori) is still the most prevalent infection of the world. Colonization of the stomach by this agent will invariably induce chronic gastritis which is a low-grade inflammatory state leading to local complications (peptic ulcer, gastric cancer, lymphoma) and remote manifestations. While H. pylori does not enter circulation, these extragastric manifestations are probably mediated by the cytokines and acute phase proteins produced by the inflammed mucosa. The epidemiologic link between the H. pylori infection and metabolic changes is inconstant and controversial. Growth delay was described mainly in low-income regions with high prevalence of the infection, where probably other nutritional and social factors contribute to it. The timely eradication of the infection will lead to a more healthy development of the young population, along with preventing peptic ulcers and gastric cancer An increase of total, low density lipoprotein and high density liporotein cholesterol levels in some infected people creates an atherogenic lipid profile which could promote atherosclerosis with its complications, myocardial infarction, stroke and peripheral vascular disease. Well designed and adequately powered long-term studies are required to see whether eradication of the infection will prevent these conditions. In case of glucose metabolism, the most consistent association was found between H. pylori and insulin resistance: again, proof that eradication prevents this common metabolic disturbance is expected. The results of eradication with standard regimens in diabetics are significantly worse than in non-diabetic patients, thus, more active regimens must be found to obtain better results. Successful eradication itself led to an increase of body mass index and cholesterol levels in some populations, while in others no such changes were encountered. Uncertainities of the metabolic consequences of H. pylori infection must be clarified in the future.

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

Background: Experience inHelicobacter pylorieradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended.Aim: To evaluate the efficacy and safety of first‐line and rescue treatments in patients allergic to penicillin in the “European Registry ofH pylorimanagement” (Hp‐EuReg).Methods: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management ofH pyloriinfection. An e‐CRF was created on AEG‐REDCap. Patients with penicillin allergy were analyzed until June 2019.Results: One‐thousand eighty‐four patients allergic to penicillin were analyzed. The most frequently prescribed first‐line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera^®; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases.Conclusion: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first‐line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results.

Background: Clarithromycin (Cla) heteroresistance of Helicobacter pylori (H pylori) infections is commonly assessed by comparing the resistance status of antrum and corpus biopsy samples and by demonstrating the discrepancy between them (interniche heteroresistance). However, fluorescence in situ hybridization (FISH) technique is capable of showing the synchronous presence of susceptible and resistant bacteria (intraniche heteroresistance), enabling the detection of heteroresistant H pylori populations within one biopsy sample.Materials and Methods: Antrum and corpus biopsy specimens of 305 H pylori‐infected patients were investigated with an rRNA‐targeted Cla‐resistance FISH test. Anamnestic data were collected from the institutional electronic register. Prevalence rates of susceptible, homo‐ and heteroresistant cases were correlated with the anamnestic and clinicopathological data.Results: Overall Cla‐resistance rate was 23.9% (73 cases), consisting of 35 (11.5%) homoresistant and 38 (12.5%) heteroresistant cases. Thirty‐five patients had at least one biopsy site where susceptible and resistant bacteria were present simultaneously. From this subset, 20 cases demonstrated intraniche heteroresistance on both sites. Prior Cla‐based eradication attempts were more frequent in homoresistant than in susceptible and heteroresistant cases (P < .001, P < .001, respectively). Cla‐containing therapy eradicated heteroresistant infections at a significantly lower rate in comparison with susceptible cases (P = .0112), but more effectively than homoresistants (P = .0393).Conclusions: The most frequent type of Cla‐heteroresistance is the coexistence of susceptible and resistant H pylori bacteria in the same location (intraniche heteroresistance). A previous Cla‐based eradication attempt predisposes patients to homoresistant infection. Heteroresistance is characterized by a non‐eradication‐related background and intermediate characteristics in many respects when compared to susceptible and homoresistant cases.

The subject of Helicobacter pylori continues to elicit worldwide interest in many research fields. Epidemiological data suggest that the prevalence of the infection is decreasing in Western/developed countries and even in some developing regions, but this is masked by the high prevalence in the most populous regions. Chronic gastritis, caused invariably by the bacterium, was again classified in Kyoto and Helicobacter pylori-associated gastritis was included as a distinct entity. The prevalence of peptic ulcers is decreasing, but bleeding ulcers are a challenging problem, with stable mortality levels even in the endoscopic era. With the extended use of endoscopy, gastric polyps (GP) have become more prevalent: some are associated with the infection, some are not. Autoimmune and Helicobacter-induced gastritis can share common pathogenetic mechanisms. Gastric cancer (GC) is ranked highly on mortality lists worldwide. Its surgical treatment has registered some progress though. Little, if any improvement has been achieved in the medical treatment of advanced GC. With proper organization, GC seems a preventable disease. In spite of many guidelines, the Pan-European registry of Helicobacter pylori management shows that eradication rates obtained in many places are suboptimal. A new therapeutic regimen was compiled with promising pilot results. The results obtained with vonaprazan are limited to Asia. New avenues of both antibiotic and non-antibiotic treatments are expected to accelerate the eradication of this ulcerogenic and carcinogenic bacterium.

Although discovered 40 years ago, Helicobacter pylori infection is still raising diagnostic and therapeutic problems today. The infection is currently managed based on statements in several guidelines, but implementing them in practice is a long process. Increasing antibiotic resistance and weak compliance of the patients limit the efficacy of eradication regimens, leaving much room for improvement. Third-generation proton pump inhibitors have added little to the results of the first two generations. Potassium-competitive acid blockers have a stronger and longer inhibitory action of acid secretion, increasing the intragastric pH. They obtained superior results in eradication when compared to proton pump inhibitors. Instead of innovative antibiotics, derivatives of existing antimicrobials were developed; some new fluoroquinolones and nitazoxanide seem promising in practice, but they are not recommended by the guidelines. Carbonic anhydrase inhibitors have both anti-secretory and bactericidal effects, and some researchers are expecting their revival in the treatment of infection. Capsules containing components of the eradication regimens have obtained excellent results, but are of limited availability. Probiotics, if containing bacteria with anti-Helicobacter pylori activity, may be useful, increasing the rates of eradication and lowering the prevalence and severity of the side effects.