Effectiveness of Helicobacter pylori Treatments According to Antibiotic Resistance.

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.

Empirical rescue treatment of Helicobacter pylori infection in third and subsequent lines: 8-year experience in 2144 patients from the European Registry on H. pylori management (Hp-EuReg).

OBJECTIVE: To evaluate the use, effectiveness and safety of Helicobacter pylori empirical rescue therapy in third and subsequent treatment lines in Europe. DESIGN: International, prospective, non-interventional registry of the clinical practice of European gastroenterologists. Data were collected and quality reviewed until October 2021 at Asociación Española de Gastroenterología-Research Electronic Data Capture. All cases with three or more empirical eradication attempts were assessed for effectiveness by modified intention-to-treat and per-protocol analysis. RESULTS: Overall, 2144 treatments were included: 1519, 439, 145 and 41 cases from third, fourth, fifth and sixth treatment lines, respectively. Sixty different therapies were used; the 15 most frequently prescribed encompassed >90% of cases. Overall effectiveness remained <90% in all therapies. Optimised treatments achieved a higher eradication rate than non-optimised (78% vs 67%, p<0.0001). From 2017 to 2021, only 44% of treatments other than 10-day single-capsule therapy used high proton-pump inhibitor doses and lasted ≥14 days. Quadruple therapy containing metronidazole, tetracycline and bismuth achieved optimal eradication rates only when prescribed as third-line treatment, either as 10-day single-capsule therapy (87%) or as 14-day traditional therapy with tetracycline hydrochloride (95%). Triple amoxicillin-levofloxacin therapy achieved 90% effectiveness in Eastern Europe only or when optimised. The overall incidence of adverse events was 31%. CONCLUSION: Empirical rescue treatment in third and subsequent lines achieved suboptimal effectiveness in most European regions. Only quadruple bismuth-metronidazole-tetracycline (10-day single-capsule or 14-day traditional scheme) and triple amoxicillin-levofloxacin therapies reached acceptable outcomes in some settings. Compliance with empirical therapy optimisation principles is still poor 5 years after clinical practice guidelines update. TRIAL REGISTRATION NUMBER: NCT02328131.

Helicobacter pylori heteroresistance to clarithromycin in adults-New data by in situ detection and improved concept.

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.

Sensitivity of Helicobacter pylori detection by Giemsa staining is poor in comparison with immunohistochemistry and fluorescent in situ hybridization and strongly depends on inflammatory activity.

BACKGROUND: Conventional stainings (including H&E and special stains like Giemsa) are the most widely applied histopathologic detection methods of Helicobacter pylori (HP). MATERIALS AND METHODS: We aimed to compare the diagnostic performance of Giemsa staining with immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) on a monocentric cohort of 2896 gastric biopsies and relate results to histologic alterations in order to find such histopathologic subgroups in which these methods underperform. All cases were categorized regarding presence or absence of chronic gastritis, inflammatory activity, and mucosal structural alterations. RESULTS: Giemsa revealed 687 cases (23.7%), IHC 795 cases (27.5%), and FISH 788 cases (27.2%) as being HP positive. Giemsa showed significantly lower overall sensitivity (83.3%) compared to IHC (98.8%) and FISH (98.0%). Moreover, the sensitivity of Giemsa dramatically dropped to 33.6% in the nonactive cases. We found that sensitivity of Giemsa strongly depends on HP density and, accordingly, on the presence of activity. Structural alterations (intestinal metaplasia, atrophy, etc.) had only no or weak effect on sensitivity of the three stainings. Both IHC and FISH proved to be equally reliable HP detecting techniques whose diagnostic performance is minimally influenced by mucosal inflammatory and structural alterations contrary to conventional stainings. CONCLUSIONS: We highly recommend immunohistochemistry for clinically susceptible, nonactive chronic gastritis cases, if the conventional stain-based HP detection is negative. Moreover, we recommend to use IHC more widely as basic HP stain. Helicobacter pylori FISH technique is primarily recommended to determine bacterial clarithromycin resistance. Furthermore, it is another accurate diagnostic tool for HP.

[Fructose and fructose intolerance]. / A fruktóz és a fruktózintolerancia.

Although fructose was discovered in 1794, it was realised in recent decades only that its malabsorption can lead to intestinal symptoms while its excessive consumption induces metabolic disturbances. Fructose is a monosaccharide found naturally in most fruits and vegetables. Dietary intake of fructose has gradually increased in the past decades, especially because of the consumption of high fructose corn syrup. With its 16.4 kg/year consumption, Hungary ranks secondly after the United States. Fructose is absorbed in the small intestine by facilitated transport mediated by glucose transporter proteins-2 and -5, and arrives in the liver cells. Here it is transformed enzymatically into fructose-1-phosphate and then, fructose-1,5-diphosphate, which splits further into glyceraldehyde and dihydroxyacetone-phosphate, entering the process of glycolysis, triglyceride and uric acid production. The prevalence of fructose intolerance varies strongly, depending on the method used. The leading symptoms of fructose intolerance are similar, but less severe than those of lactose intolerance. Multiple secondary symptoms can also occur. A symptom-based diagnosis of fructose intolerance is possible, but the gold standard is the H2 breath test, though this is less accurate than in lactose testing. Measuring fructosaemia is costly, cumbersome and not widely used. Fructose intolerance increases intestinal motility and sensitivity, promotes biofilm formation and contributes to the development of gastrooesophageal reflux. Long-term use of fructose fosters the development of dental caries and non-alcoholic steatohepatitis. Its role in carcinogenesis is presently investigated. The cornerstone of dietary management for fructose intolerance is the individual reduction of fructose intake and the FODMAP diet, led by a trained dietetician. The newly introduced xylose-isomerase is efficient in reducing the symptoms of fructose intolerance. Orv. Hetil., 2016, 157(43), 1708-1716.

[Lactose intolerance: past and present. Part 1]. / A laktózintoleranciáról: Múlt és jelen - I. rész.

Lactose intolerance is the most prevalent intestinal malabsorption disorder. After presentation of its history, the author describes the emergence of lactose intolerance during the evolution of species, and the biochemistry of lactose as well as features of human and bacterial lactase enzymes are then described. The unequal distribution of lactose intolerance in different continents and population is discussed, followed by presentation of past and present prevalence data in Hungary. Adult-type hypolactasia is caused by a polymorphism of the MCM6 gene located upstream from the lactase gene on the long arm of the chromosome 2. It can be determined with the polymerase chain reaction. The intestinal symptoms of lactose intolerance are well known, but its extra-intestinal manifestations are less recognised. Invasive diagnostic methods (determination of lactase activity from small intestinal biopsies, lactose tolerance test), are accurate, but have been replaced by the non-invasive methods; their gold standard is the H2 breath test. Genetic testing is being used more and more frequently in Hungary too, and, presumably, the methane breath test will be also available in the near future. Lactose intolerance can be accompanied by inflammatory bowel diseases, coeliac disease and irritable bowel syndrome; it could be established whether this association is causal or not in order to start a correct diet and therapy.

[Lactose intolerance: past and present. Part II]. / A laktózintoleranciáról: Múlt és jelen - II. rész.

The author summarises the interrelations between lactose intolerance, calcium and vitamin D metabolism and osteoporosis. Lactose intolerance enhances the risk of forearm and hip fractures in some patients. Lactase gene genotype and fracture risk are related in some populations. Calcium and vitamin D supplementation increase bone mineral content and they are justified in children, during pregnancy and lactation, and in postmenopausal women. The intake of milk and milk products could increase the risk of ovarian carcinoma. CC genotype of the lactase gene increased the risk of colorectal carcinoma in Finns; no such effect was observed in British, Spanish and Italian patients. Even small quantities of lactose in drugs (10-750 mg) could elicit intolerance symptoms due to individual susceptibility. In spite of public knowledge and advertising, controlled studies did not prove the beneficial effect of either a lactose-free diet, enzyme supplementation or probiotics in an evidence-based manner. While accepted guidelines are lacking, a personalised therapy is mandatory. In spite of increasing public interest in lactose intolerance, many unknown factors must still be studied.

[Helicobacter pylori -- 2014]. / Helicobacter pylori -- 2014.

The author reviews the main achievements in Helicobacter pylori research in the past 2 years. Of the more than 1000 microRNAs described thus far, sets of over- and underexpressed samples were identified that are associated with either gastric cancer or precancerous lesions, and some of them could be either markers or therapeutic targets in the near future. Meta-analyses involved 95 new publications: the association between infection and oesophageal, colorectal, pancreatic and liver carcinomas is supported by the increased odds ratios, but the results do not reach the strength seen in gastric carcinoma. Epstein-Barr virus is an emerging pathogen: 10% of gastric cancers are virus-associated; the prevalence of the virus in normal mucosa, chronic gastritis and peptic ulcer are currently being studied. Current Helicobacter pylori eradication regimens frequently achieve suboptimal results: a few optimisation methods are presented, although not all are supported by the meta-analyses. In 2013, the European Helicobacter Study Group proposed the development of a pan-European registry; data from 5792 patients registered so far indicated that many therapeutic regimens resulted in a low eradication rate. In 2013, the Healthy Stomach Initiative was started with the aim of supporting and disseminating research performed in the field of healthy and diseased stomachs.

Role of compliance in Helicobacter pylori eradication treatment: Results of the European Registry on H. pylori management.

BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.

[Probiotics in gastroenterology -- from a different angle]. / Probiotikumokról a gasztroenterológiában -- kicsit másképp.

After a short overview of the history of probiotics, the author presents the development of human intestinal microflora based on the newest genetic data and the microbiological features of main probiotics. The indications of probiotic administration have been defined and extended in recent years. The author reviews significant results of probiotic treatment in some gastrointestinal diseases based on meta-analytical data. Probiotics are useful in preventing and treating diarrhoea caused by antibiotics and Clostridium difficile caused diarrhoea. In the treatment of Helicobacter pylori infection, preparations containing certain Lactobacillus,Bifidobacterium strains or Saccaromyces boulardii could enhance by 5-10% the rate of successful eradication and reduce the incidence and severity of the side effects. Some symptoms of irritable bowel syndrome and thus the quality of life can be improved by probiotics. Their beneficial effect in ulcerative colitis was proven, while in Crohn's disease has not yet been defined. The use of probiotics is not included in guidelines, with the exception of the Maastricht IV/Florence consensus. For each disease it is advisable to use probiotics containing strains only with proven beneficial effect. The efficiency of preparations containing mixed strains has not yet been properly investigated. The author reviews the rare but potentially serious side effects of probiotics. In Hungary, there are many probiotic preparations available which can be purchased in pharmacies without prescription: their use is more empirical than evidence-based. The European Food Safety Authority has recently rejected claims for probiotics to be classed as medicines given the lack of convincing evidence on the effects of probiotics on human health and well-being. Clearly, further research is needed to collect evidence which could be incorporated into the international guidelines.

[History of tumor markers for cancers of the digestive system]. / Az emésztoszervi tumorjelzok története.

Tumor markers are gene products which signal the occurrence of tumors in different organs as well as their response to surgery and chemotherapy. The discovery of tumor markers occurred after the demonstration of tumor-specific transplantation antigens in chemically or virally induced tumors in syngenic rodents. The history of currently used tumor markers began in the 1940s, the first discovered being alpha-fetoprotein in 1956, followed by that of carcinoembryonic antigen in 1965. Since then the range of tumor markers has widened continously. Their chemical structure and genetics is now well known. Some may play part in tumor growth and development of metastases. The potential uses of tumor markers are general or high risk population screening, adjunct in diagnosis of cancer, preoperative indicator of tumor burden, indicator of therapeutic success, evidence of postoperative recurrences and use in tumor localization. However, there is no ideal tumor marker fulfilling all the criteria. Isotope-labeled anti-carcinoembryonic antigen antibodies and small molecular E-selectin inhibitors could play a role in the molecular radio- and chemotherapy of colon and pancreatic carcinomas.

[Changing prevalence of Helicobacter pylori infection in the 9th district of Budapest. A retrospective endoscopic study, 1997-2012]. / A Helicobacter pylori-fertozés epidemiológiája Ferencvárosban. Retrospektív endoszkópos tanulmány, 1997-2012.

BACKGROUND: The prevalence of Helicobacter pylori infection in developed countries is decreasing. The time-frame of this process is largely unknown. AIM: The aim of the authors was to evaluate the changes in the prevalence of Helicobacter pylori infection in their endoscopic centre. METHODS: This retrospective study included 4647 patients examined between 1997 and 2012. Helicobacter pylori was determined from antral and corpus biopsies by the modified Giemsa stain and rapid urease test. The prevalence of the infection was calculated yearly for the period studied, for age decades from 18 to 85 years, birth cohorts of 10 years from 1920 to 1994 and according to diagnosis. RESULTS: The overall prevalence of Helicobacter pylori infection was 54.7%, which decreased from 71.3% in 1997 to 32.76% in 2011. Functional dyspepsia was found in 37.9%, duodenal ulcer in 25.3%, gastric ulcer in 3.8% and reflux disease in 24.2% of the patients. The mean prevalence of infection was 62.5% in birth cohorts of 10 years between 1920 and 1959, 57.4% in those between 1960 and 1969, and decreased to 39.0% and 26.7% in birth cohorts between 1970 and 1979) and between 1980 and 1989, respectively. According to age cohorts, the prevalence was 21.8% 34.9%, 46.5%, 63.7%, 63.2% and 59.2% in patients aged 18-19 years, 20-29 years, 30-39 years, 40-49 years, 50-59 years and 60-69 years, respectively. The proportion of H. pylori positive duodenal ulcers decreased from 95.9% in 1998 to 59.1% in 2011 (p = 0.001). CONCLUSIONS: The prevalence of Helicobacter pylori infection in the 9th district of Budapest is decreasing, especially in cohorts born in the late 1960s and 1970s, nearly 1.5 decades before the discovery of the bacterium.

Newer, Older, and Alternative Agents for the Eradication of Helicobacter pylori Infection: A Narrative Review.

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.

Comparison of the management of Helicobacter pylori infection between the older and younger European populations.

The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. "European Registry on H. pylori Management (Hp-EuReg)" data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18-59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p < 0.05). The overall second-line mITT treatment effectiveness was 84% in both groups. The effectiveness of the most frequent first- and second-line triple therapies was suboptimal (< 90%) in both groups. Optimal efficacy (≥ 90%) was achieved by using bismuth and non-bismuth-based quadruple therapies. In conclusion, the approach to the diagnostics and treatment of H. pylori infection did not generally differ between younger and older patients. Main differences were reported in the concurrent medications, allergy to penicillin and adverse events both in first- and second-line treatment. Optimal effectiveness rates were mostly achieved by using bismuth and non-bismuth-based quadruple therapies. No clinically relevant differences in the effectiveness between the age groups were observed.

[Helicobacter pylori - 2012]. / Helicobacter pylori - 2012.

The author overviews some aspects of literature data of the past 2 years. Genetic research has identified polymorphisms of Helicobacter pylori virulence factors and the host which could play a role in the clinical outcome of the infection (peptic ulcer or gastric cancer). So far they have been performed in research centers but with a decrease of costs, they will take their place in diagnosing the diseases and tailoring the treatment. Antibiotic resistance is still growing in Southern European countries and is decreasing in Belgium and Scandinavia. Currently, the clarithromycin resistance rate is of 17-33% in Budapest and levofloxacin resistance achieved 27%. With careful assessment of former antibiotic use the resistance to certain antibiotics can be avoided and the rates of eradication improved. Immigration is a growing problem worldwide: according to Australian, Canadian and Texan studies, the prevalence of Helicobacter pylori is much higher in the immigrant groups than in the local population. An Italian study showed that the eradication rate of triple therapy is significantly lower in the Eastern European immigrants than in the Italians. A recent research has suggested a link between female/male infertility, habitual abortion and Helicobacter pylori infection. However, there are no published data or personal experience to show whether successful eradication of the virus in these cases is followed by successful pregnancies or not. The author overviews the Maastricht process and analyzes the provisions of the Maastricht IV/Florence consensus, in which the new diagnostic algorithms and indications of eradication therapy are reformulated according to the latest levels of evidence and recommendation grading. According to the "test and treat" strategy, either the urea breath test or the stool monoclonal antigen test are recommended as a non-invasive diagnostic method in primary care. Endoscopy is still recommended in case of alarm symptoms, complicated ulcer, or if there is a suspicion of malignancy or MALT lymphoma. Local resistance to clarithromycin and levofloxacin should be considered in the choice of first-line therapy, in case of levels >15-20% these compounds should not be used. In regions with low resistance rates, classical triple therapy remains the regimen of choice; its alternative is the bismuth-based quadruple therapy. Determining antimicrobial resistance is justified after failed second- or third-line therapies; where available, molecular methods (fluorescence in situ hybridization, polymerase chain reaction) should be used. As second/third line treatments, the sequential, bismuth-based quadruple, concomitant quadruple regimens, hybrid are all possible alternatives. The Hungarian diagnostic and therapeutic approach in practice is different in some aspects from the provisions of the European consensus. Orv. Hetil., 2012, 153, 1407-1418.

Helicobacter pylori - 2021. / Helicobacter pylori - 2021.

Összefoglaló. A Helicobacter pylori továbbra is a világ legelterjedtebb fertozése: prevalenciája a fejlodo országokban 70-80%, a fejlett országokban csökkeno tendenciát mutat. A dél-magyarországi véradókban a prevalencia 32%-ra csökkent. A migráció a befogadó ország számára a fertozés fokozott kockázatával jár. A szövettani diagnózisban az immunhisztokémiai vizsgálat pontosabb a hagyományos Giemsa-festésnél. A mesterséges intelligencia érzékenysége a hagyományos endoszkópiáéval összehasonlítva 87%, pontossága 86%. Az újgenerációs szekvenálással lehetséges egy biopsziás mintából több antibiotikumérzékenység meghatározása. A Helicobacter pylori kezelésének európai regisztere kimutatta, hogy 2013 és 2018 között a bizmutalapú négyes vagy a 14 napos egyideju négyes kezelések hatásosabbak, mint a hagyományos hármas kezelés, de elterjedésük igen lassú folyamat, jelentos földrajzi különbségekkel. Az új típusú koronavírus (SARS-CoV-2) felléphet Helicobacter pylori fertozésben is, egymás kóros hatását felerosítve. A diagnosztikai módszerek korlátozottak. Protonpumpagátlók szedése növeli a COVID-19-fertozés kockázatát és annak súlyos kimenetelét. Elozetesen ismert peptikus fekély, vérzés, illetve antikoguláns kezelés elott az eradikáció a vírusos fertozés lezajlása után indokolt. A probiotikumoknak az eradikációra gyakorolt hatásáról 20, közepes minoségu metaanalízis született, így a konszenzusokban foglalt álláspontok sem egyértelmuek: a jövoben ezt tisztázni kell. Orv Hetil. 2021; 162(32): 1275-1282. Summary. Helicobacter pylori is still the most widespread infection in the world: its overall prevalence is 70-80% in developing regions, but fortunately it is decreasing in the Western world. The prevalence in blood donors from South-Eastern Hungary decreased from 63% in the 1990's to 32% in 2019. Migration constitutes an increased risk of infection for the destination countries. Immunohistochemistry has proven to be more accurate in histological diagnosis than the conventional Giemsa stain. The sensitivity and accuracy of artificial intelligence as compared to videoendoscopy were 87% and 86%, respectively. The European Register on the management of Helicobacter pylori infection revealed that concomitant quadruple and 14-day bismuth-based therapies are more efficient than triple combinations, although their incorporation in practice is a long-lasting process, with large geographical variations. The novel type of coronavirus (SARS-CoV-2) can also occur in Helicobacter pylori-infected patients, mutually enhancing their pathogenetic effects. Diagnostic possibilities are limited in this setting. The use of proton pump inhibitors increases the risk of viral infection and the severity of the disease. Eradication treatment seems justified in patients with previously known peptic ulcers or gastrointestinal bleeding, or before starting anticoagulant treatment, but must be postponed after resolution of viral infection. The effect of probiotics on eradication was addressed by 20, medium-to-low quality meta-analyses and so, the recommendations of the guidelines are equivocal, which must be clarified in the future with higher quality studies. Orv Hetil. 2021; 162(32): 1275-1282.

Efficacy of Clarithromycin Depends on the Bacterial Density in Clarithromycin-Heteroresistant Helicobacter pylori Infections: An In Situ Detected Susceptibility and Quantitative Morphometry-Based Retrospective Study.

The global rise in clarithromycin (Cla) resistance is considered to be the main contributor of Helicobacter pylori (Hp) eradication failures. In nearly half of the Cla-resistant Hp infections, Cla-susceptible bacteria are simultaneously present with the Cla-resistant ones (Cla-heteroresistance). The proportion of resistant bacteria in the bacterial population (R-fraction) and its predictive role for the use of Cla-based therapies in Cla-heteroresistant infections has not yet been investigated. Our retrospective study analyzed gastric biopsy samples of 62 Hp-positive patients with Cla-heteroresistant infection. Fluorescence In Situ Hybridization technique was used to visualize the coexistence of resistant and susceptible bacteria within one tissue sample. R-fraction was quantified on multichannel microimages by digital morphometry. Resistant bacteria had a patchy distribution within the whole bacterial population causing high diversity among the investigated areas. Patients were subdivided into two major groups according to whether a Cla-based eradication attempt was conducted before or after the biopsy sampling. R-fraction was significantly lower among cases having only one previous Cla-based eradication attempt vs. those that had multiple previous eradications, including at least one Cla-containing therapy (0.41 vs. 0.89, p = 0.0308). Majority of the patients without previous eradication attempt had successful eradication with Cla-containing regimen (59.26%), verified by a negative 13C-urea breath test or control biopsy. Multivariable model indicated that the therapeutic outcome using Cla-based regimens depended on the bacterial density rather than the R-fraction. Our study raises the potential use of Cla-containing eradication therapies in certain Cla-heteroresistant Hp infections, taking into account the possible predictive role of bacterial density.

Primary and secondary clarithromycin resistance in Helicobacter pylori and mathematical modeling of the role of macrolides.

Clarithromycin is a macrolide antibiotic widely used for eradication of Helicobacter pylori infection, and thus resistance to this antibiotic is a major cause of treatment failure. Here, we present the results of a retrospective observational study of clarithromycin resistance (Cla-res) in 4744 H. pylori-infected patients from Central Hungary. We use immunohistochemistry and fluorescence in situ hybridization on fixed gastric tissue samples to determine H. pylori infection and to infer Cla-res status, respectively. We correlate this information with macrolide dispensing data for the same patients (available through a prescription database) and develop a mathematical model of the population dynamics of Cla-res H. pylori infections. Cla-res is found in 5.5% of macrolide-naive patients (primary Cla-res), with no significant sex difference. The model predicts that this primary Cla-res originates from transmission of resistant bacteria in 98.7% of cases, and derives from spontaneous mutations in the other 1.3%. We find an age-dependent preponderance of female patients among secondary (macrolide-exposed) clarithromycin-resistant infections, predominantly associated with prior use of macrolides for non-eradication purposes. Our results shed light into the sources of primary resistant cases, and indicate that the growth rate of Cla-res prevalence would likely decrease if macrolides were no longer used for purposes other than H. pylori eradication.

[Helicobacter pylori -- 2010]. / Helicobacter pylori -- 2010.

Helicobacter pylori, discovered 27 years ago, has remained the most prevalent infectious agent in the world. In the author's hypothesis, the increase of peptic ulcer prevalence in the 19-20th century could be attributable to the extended worldwide use of gastric tubes for secretory testing which led to the iatrogenic transmission of pathogenic strains. Helicobacter pylori outer membrane proteins (OMP), and duodenal ulcer promoting (dupA) proteins were identified as novel virulence factors, leading to the production of pro-inflammatory cytokines, which could be future targets of therapy. There is no ideal first-line eradication of the infection and according to expert's opinion, the efficiency of these regimens has fallen gradually in recent years to unacceptably low levels; however, in the author's opinion this is a multifactorial phenomenon which can not be generalized. As alternative drugs, the efficiency of levofloxacin, furazolidone and rifabutin has been proven by meta-analyses. Sequential and bismuth-free quadruple therapies, although highly efficient, are not yet used on a large scale. The recurrence of the infection is 2.27%/year in developed and of 13.0%/year in developing countries. Spontaneous eradication occurred in 8-20% of the children and 5-11% of adults. The prevalence of clarithromycin resistance is increasing worldwide. In Hungary, it has reached 10.9% in county cities, according to a national survey. In a district of Budapest called Ferencváros, the prevalence between 2005 and 2009 was 16-22%, with no increasing trend. The development of enzymatic inhibitors (urease, carbonic anhydrase and gamma-glutamyl transpeptidase), modified antibiotics and efflux pump inhibitors seem promising ways because these compounds do not lead to resistance; however, none have yet been used in humans.