Helicobacter pylori and some aspects of gut microbiota in children.

Helicobacter pylori infection in children differs from infection in adults in many aspects. The rate of infection, epidemiology, clinical presentations and complications, the applicability of diagnostic tests, antibiotic resistance, treatment options, and success rates differ significantly. Due to all these differences, management guidelines for children and adults differ also substantially. In 2017, the Updated ESPGHAN and NASPGHAN Guidelines on the management of H. pylori infection in children were published, emphasizing the differences in clinical presentation and indications for treatment, stating that the primary goal of clinical investigation in children is to identify the cause of upper gastrointestinal symptoms rather than the presence of H. pylori infection. Therefore, the diagnosis should be based on upper endoscopy, and the "test and treat strategy" should not be used in children. Due to an increasing rate of antibiotic resistance worldwide, the updated guidelines recommend broader use of antimicrobial susceptibility testing for H. pylori strains in order to tailor eradication treatment accordingly. Moreover, treatment in children should be prescribed only when indicated and should be based on the rate of eradication in local populations aiming for treatment success above 90%. During the last two decades there has been a steady decrease in the rate of H. pylori infection in both children and adults in the Western world. Two recent publications studying the incidence of H. pylori infection confirmed that early childhood is a time for acquisition of infection both in industrialized and nonindustrialized countries. In addition, they showed that H. pylori could be acquired outside the family. In respect to the inverse association between H. pylori and allergy, a longitudinal study demonstrated that early exposure to H. pylori at any age was inversely associated with atopy and allergic conditions.

Antimicrobial resistance and characteristics of eradication therapy of Helicobacter pylori in Japan: a multi-generational comparison.

BACKGROUND: Eradication of Helicobacter pylori (H. pylori) at a younger age is considered to be effective in preventing gastric cancer. This study assessed the characteristics of eradication therapy in young patients. MATERIALS AND METHODS: We enrolled 1073 patients with H. pylori infection between 2000 and 2013. The subjects were divided into three groups according to age into the young (≤30 years), middle-aged (31-50 years), and elder (≥51 years) groups. We also examined 472 cases to investigate clinical eradication characteristics. RESULTS: The rate of clarithromycin (CAM) resistance was 57.9%, 34.5%, and 35.2% in the young, middle-aged, and elder group, respectively, in 2012-2013 and was significantly higher in the young group than in the elder group (p = .01). Metronidazole (MNZ) resistance was similar among the three groups at each time point. While CAM resistance rose over the study period, MNZ resistance was noted to have decreased of late. The overall initial eradication success rate was 91.9% (95% CI, 89.1-94.1) in our cohort. Eradication efficiency was comparable in the young, middle-aged, and elder group at 94.3% (95% CI, 87.4-97.5), 90.2% (95% CI, 82.9-94.6), and 91.8% (95% CI, 88.1-94.5) respectively. Side effects such as skin rash were observed in 14.8%, 3.9%, and 3.5% of the respective groups. There were significant differences in the incidence of side effects between the young group and other groups (p < .05, respectively). CONCLUSION: Since CAM resistance and the incidence of side effects are higher in young individuals, it is especially important to select eradication regimens based on testing for antimicrobial susceptibility.

Helicobacter pylori infection--management from a European perspective.

Since the first European Consensus Report on Helicobacter pylori management in 1996 and the strong indication for therapy of peptic ulcer disease and other benign gastroduodenal pathologies, the list of indications for therapeutic interventions has been extended to selected extradigestive diseases. Test-and-treat and search-and-treat strategies have been implemented for patients with dyspeptic symptoms and prevention of H. pylori-related complications (gastric cancer included), respectively. Screen and treat strategies are in discussion but are still lacking any structured implementation. For diagnosis of H. pylori, accurate noninvasive and endoscopy-based tests are widely available across Europe, and individual tests are selected according to patient needs and clinical settings. Standard proton pump inhibitor-based triple therapy faces increasing failure rates mainly because of clarithromycin resistance, but alternative first-line options bismuth quadruple, or non-bismuth quadruples in various combinations have emerged as effective first-line alternatives. After treatment failure, defined rescue therapies including individual antibiotic-sensitive testing are recommended.

Clinical management of Helicobacter pylori--the Japanese perspective.

BACKGROUND: After the approval of health insurance coverage of eradication therapy for Helicobacter pylori-positive peptic ulcer disease (PUD) in 2000, comprehensive coverage for H. pylori infection itself was implemented in 2013. METHODS: We did a literature search using PubMed database on the management of H. pylori infection including indications, regimens, outcomes of current eradication therapies, trends of antibiotic resistance rates and proposed third-line rescue therapy in Japan. We also collected data on changes of eradication rates in our hospital by searching electronic medical records. RESULTS: After implementation of insurance coverage of eradication therapy for PUD, dramatic reduction of the number patients with PUD as well as spending on ulcer drug was documented. According to the current regulation, proton pump inhibitor (PPI)-based triple therapy with 2 antibiotics, amoxicillin (AMPC) plus clarithromycin, for 7 days is approved as the first-line therapy. After failure of the first-line therapy, PPI plus AMPC and metronidazole is authorized as the second line, which maintains an excellent eradication rate of over 90% in Japan. When these two therapies fail, a sitafloxacin-based therapy seems to be most promising among many rescue regimens. CONCLUSION: Comprehensive public health insurance coverage of H. pylori infection will promote eradication in Japanese people infected with H. pylori, whose risk of developing gastric cancer has been shown to be high. It also provides us a unique opportunity to study whether the broader indications can accelerate the reduction of gastric cancer in Japan in the same way we witnessed the reduction of PUD.

Antimicrobial resistance of H. pylori to the outcome of 10-days vs. 7-days Moxifloxacin based therapy for the eradication: a randomized controlled trial.

INTRODUCTION: Antibiotic resistance decreases success of Helicobacter pylori (Hp) eradication. Recently published results show low rate of resistance and better compliance with moxifloxacin based regiments. AIMS&METHODS: Whether 7 days moxifloxacin with lansoprasole and amoxycillin can be compared with 10 days moxifloxacin with lansoprasole and amoxycillin according to moxifloxacin resistance. Patients with non-ulcer dyspepsia who had culture and histology positive Hp infection (n = 150) were randomly assigned into two groups. The first group (n = 75) received moxifloxacin 400 mg/d during 7 days and the other (n = 75) received moxifloxacin 400 mg/d during 10 days. All patients received amoxycillin 1 g twice daily, lansoprasole 30 mg twice daily. All Hp cultures were tested for sensitivity to moxifloxacin. RESULTS: 138 patients (92%) completed the study, 68 in the first group and 70 in the second. Eradication rates were 84% (57/68) and 76% (57/75) in the 7 days moxifloxacin group and 90% and 84% in the second group (63/70, 63/75) according to the PP and ITT analysis; p = n.s. Among 129 patients (86% of study group), 6% of strains were primary resistant to moxifloxacin. Eradication of moxifloxacin sensitive/resistant strains was 98%/66%, p < 0.05. CONCLUSION: According to our results we recommend 7 days moxiflixacin based triple therapy.

Helicobacter spp. other than Helicobacter pylori.

Non-H. pylori Helicobacter species (NHPHS) are associated with several important human and animal diseases. In the past year research into this group of bacteria has continued to gain attention, and novel species have been described in new niches owing to improvements in detection methods. Polymerase chain reaction and/or sequencing remain the gold standard for the detection of this genus. New insights into the pathogenesis of the NHPHS in hepatobiliary, gastric, and intestinal diseases were gained. In particular, data revealed interaction between hepatic steatosis and infectious hepatitis in the development of hepatocellular carcinoma. Evidence of an association between hepatitis C virus and Helicobacter spp. in hepatocarcinoma development was also provided; and male sex hormone signaling appeared to influence infectious hepatitis induced by Helicobacter hepaticus. More findings support an association between Helicobacter heilmannii and gastric adenocarcinoma; and in mice, mucins MUC4 and MUC5 but not MUC1 influence the colonization and pathogenesis of Helicobacter felis. Data indicated that the roles of the adaptive immune system in H. hepaticus-induced intestinal tumorigenesis are different in the small and large intestines, and environmental factors, such as bile acids may modulate H. hepaticus carcinogenic potential. New reports in the prevention and eradication of NHPHS showed a protective response against Helicobacter suis induced by vaccine administration, and a successful cross-foster rederivation method successfully eradicated Helicobacter spp. from contaminated mice litters. Overall, the studies provided insights into the pathophysiology of Helicobacter species other than Helicobacter pylori.

Functional 13C-urea and glucose hydrogen/methane breath tests reveal significant association of small intestinal bacterial overgrowth in individuals with active Helicobacter pylori infection.

OBJECTIVES: Helicobacter pylori infection is considered to alter the bacterial flora in the upper gastrointestinal tract. This study aimed at investigating the presence of small intestinal bacterial overgrowth (SIBO) in patients with active H. pylori infection assessed by functional breath testing. DESIGN AND METHODS: A total of 109 outpatients, who were referred for the H. pylori13C-urea breath test (13C-UBT) by general practitioners and specialists, were also tested for the presence of SIBO by the glucose hydrogen (H2)/methane (CH4) breath test (HMBT). A detailed anamnesis was carried out about the history of H. pylori infection, eradication therapies, proton pump inhibitor intake, and comorbidities. RESULTS: In total, 36/109 (33.0%) patients had a positive H. pylori13C-UBT, and 35/109 (32.1%) patients had a positive glucose HMBT, the latter being indicative of SIBO. Interestingly, individuals with a positive H. pylori13C-UBT were significantly more often associated with a positive glucose HMBT (p=0.002). Cohen's κ measuring agreement between the 13C-UBT and the glucose HMBT was 0.31 (confidence intervals: 0.12-0.50) (p=0.001). Altogether, 19 of 54 (35.2%) patients, who had completed up to four eradication therapies, were diagnosed with SIBO by HMBT. CONCLUSIONS: H. pylori infection was found to be significantly associated with the presence of SIBO as determined by functional breath testing. In addition, SIBO rates appeared to have increased after completed eradication therapies. However, further longitudinal studies are warranted to fully elucidate the relationship and treatment modalities of coincident H. pylori infection and SIBO.

Helicobacter cinaedi knee infection after arthroscopy in an immunocompetent patient.

An otherwise healthy 36-year-old man was hospitalised due to a traumatic tear of the meniscus in the left knee. An arthroscopy was performed and his meniscus was partially resected. Thirty days later, he was rehospitalised with arthritis in the left knee and cellulitis on the left tibia. Helicobacter cinaedi was isolated from the synovial fluid, which was incubated in a BACTEC Paediatric bottle. The patient was treated with oral rifampicin and moxifloxacin for 6 weeks with good clinical response without relapse. The source of the infection was not found. The case emphasises the importance of incubating the synovial fluid in a rich medium such as a BACTEC Peds Plus/F bottle. Physicians and microbiologists should be aware of H. cinaedi as a human pathogen causing a range of disease manifestations, including infective arthritis and cellulitis, particularly if symptoms evolve in the weeks following a surgical procedure.

[Helicobacter pylori infection and ulcer]. / Helicobacter-pylori-Infektion und Ulcuskrankheit.

Our understanding of ulcer pathogenesis has dramatically changed since the discovery of Heliobacter pylori. Peptic ulcer is now recognized as a chronic gastric infectious disease. H. pylori can be considered the pacemaker, with other known risk factors ultimately contributing to the ulcer formation. Treatment of H. pylori in peptic ulcer disease cures the acute lesion and prevents relapse and complications. In clinical management a positive diagnosis of H. pylori is required and other potential causes for ulcer formation must be excluded before starting treatment. The standard treatment in H. pylori positive ulcer consists of PPI in standard dose and two antibiotics either clarithromycin 2 x 500 mg and amoxycillin 2 x 1 g or metronidazole 2 x 400 mg and clarithromycin 2 x 250 mg (or 500 mg) for 7 days. The simultaneous presence of H. pylori and NSAID intake requires distinct management. Following bleeding complication a PPI needs to be given beyond 7 days until ulcer healing is endoscopically confirmed.

[The effectiveness of 7-day combined Helicobacter eradication therapy in patients with peptic ulcer and chronic gastritis]. / Effektivnost' semidnevnogo kombinirovannogo kursa éradikatsionnoi gelikobakternoi terapii u bol'nykh iazvennoi bolezn'iu i khronicheskim gastritom.

Epidemiological and clinical findings suggest that the spread of Helicobacter pylori (H.p.) infection as an etiological and pathogenetic agent is of prime importance for patients with pelvic ulcer and chronic gastritis. However, there are relatively scanty papers on the impact of therapy against H.p. on its eradication rate, symptom arrest, and the course of diseases. A great deal of drug combinations have been proposed to eradicate H.p. infection and some of them are even classical (omeprazole in combination with 2-3 antibiotics). The H.p. eradication with this combination for 7 days is as high as 85-90%. These regimens are recommended for practical application in Europe and Russia. The authors' studies in 90 patients (34 with duodenal ulcers, 34 with gastric ulcers, and 28 with chronic duodenitis) indicate that lansofed used in 7-day combined therapy is highly effective in suppressing acid production, abolishing symptoms during an exacerbation of peptic ulcer (gastroduodenitis) and in eradicating H.p. infection. There is evidence for that the use of the agent in combination with 2 and 3 anti-H.p. drugs rapidly arrest the symptoms of a disease, frequently diminishes an inflammatory process and lead to a remission.

[Upgrading efficiency and safety of combined antihelicobacterial treatment of ulcer patients using modern clinicopharmacological approaches]. / Povyshenie éffektivnosti i bezopasnosti kombinirovannogo antikhelikobakternogo lecheniia bol'nykh iazvennoi bolezn'iu s primeneniem sovremennykh kliniko-farmakologicheskikh podkhodov.

Therapeutic monitoring of ranitidine and omeprasol using automatic analyser REMEDi HS Drug Profiling System (Bio-Rad, USA) was performed in 120 patients with morphologically verified ulcer associated with Helicobacter pylori. The addition of antibacterial drugs elevated concentration of blood ranitidine, omeprasol being stable. The highest therapeutic effectiveness was achieved with combination of ranitidine plus metronidasol and jozamycin as well as omeprasol plus metronidasol and claritromycin. Ulcer patients with concomitant hepatobiliary diseases significantly more frequently developed side effects of antihelicobacterial therapy and the rise of ranitide and omeprasol concentrations in blood can serve a prognostic criterium of their appearance. As the highest tolerance was observed in the treatment with combination ranitidine + metronidasol + oletetrin, this regimen is recommended as the safest antihelicobacterial therapy.

The presence of Helicobacter pylori in oral cavities of patients with leukoplakia and oral lichen planus

ABSTRACT Objective Helicobacter pylori infection is one of the most common bacterial infections in men. This gastrointestinal pathogen is closely related to gastritis, peptic ulcers, and the increased risk of gastric cancer. Numerous studies have indicated oral cavities as possible Helicobacter pylori reservoirs. Helicobacter pylori has been detected both in supragingival and subgingival plaques, and also in saliva. In addition, the relationship between lesions of oral mucosa and the presence of H. pylori has been evaluated and described in some studies. The aim of this study was to assess the presence of Helicobacter pylori DNA in the oral cavity of patients with oral leukoplakia and oral lichen planus. Material and Methods The study included 54 patients with oral leukoplakia, 72 with oral lichen planus lesions, and 40 healthy controls. The presence of Helicobacter pylori in oral cavity samples was analyzed using a single-step Polymerase Chain Reaction (PCR) method. All patients underwent a periodontal examination and the following clinical parameters were collected: pocket depth, bleeding, and plaque indexes. The periodontal status was assessed using the Offenbacher classification. Results In most patients, pathological lesions were in typical sites on the buccal mucosa (leukoplakia in 88%, and oral lichen planus in 93% of patients). The DNA of the Helicobacter pylori was present in 20% of patients with leukoplakia and 23% of patients with lichen planus. We did not find the DNA of H. pylori in healthy controls. The periodontal status described by periodontal indices was worse in the investigated group than in the control group. Conclusion These findings suggest that the H. pylori presence in oral cavities may be related with leukoplakia and lichen planus oral lesions.

Effective regimens for the treatment of Helicobacter pylori infection.

Successful Helicobacter pylori eradication therapy remains a challenge in medical practice. Currently, a proton pump inhibitor-based triple therapy containing clarithromycin, amoxicillin or nitroimidazole for 7 days is the recommended first-line treatment approach with an expected eradication success rate of approximately 80%. As a second-line treatment option in the case of failure, a ranitidine bismuth citrate-based quadruple therapy is currently recommended curing another 80% of patients, leaving a subset of patients with persistent H. pylori infection. For these patients, promising rescue options have been evaluated including regimens that contain rifabutin, quinolones, furazolidone or high-dose amoxicillin. The role of susceptibility testing is still under discussion. It is not generally recommended prior to first-line treatment but guidelines propose a role for culture and antibiotic sensitivity testing after failure of the second attempt. Meanwhile, data on the geographic distribution of resistance pattern are available and may guide therapeutic decisions with regard to the combination of antibiotics chosen for the individual patients aiming at 100% cure rate in each individual patient.

[Helicobacter pylori: clinical pictures of an infectious disease with pathogen persistence]. / Helicobacter pylori: Krankheitsbilder einer Infektionskrankheit mit Erregerpersistenz.

It is the aim of this paper to provide survey of the very fast developing field of medical research on Helicobacter pylori which includes as different branches as gastroenterology, pharmacology or microbiology. After examination of the several diseases, pathological mechanisms, the diagnostical techniques and the therapeutical regimens, the authors of this study favorize an early indication for eradication of helicobater pylori. Since research on Helicobacter pylori is divided into many fields, there is the attempt to come to a clear and more rational point of view concerning therapeutical strategies and management of the infection. It is another focal point to emphasize the important role that chronical gastritis induced by Helicobacter pylori plays as an important risk factor for gastric carcinoma.