The epidemiology of Helicobacter pylori resistance in a university affiliated hospital: a comparison between two time periods-a cross-sectional design.

PURPOSE: During the last few decades, the increased use of various types of antibiotics in the general population caused a significant change in regional Helicobacter pylori (H. pylori) antibiotic resistance. Our aim is to study the changes in H. pylori resistance in patients who had undergone an esophagogastroduodenoscopy (EGD) and susceptibility testing and found positive for H. pylori. The study was conducted in a university affiliated hospital between 2013-2020. METHODS: A cross-sectional study was performed on all consecutive patients who had undergone an EGD and tested positive for H. pylori at the Kaplan Medical Center, Israel. The study period was divided into two sub-periods: 2013-2016 and 2017-2020. Data on age, sex, comorbidities, previous treatments, and antimicrobial susceptibility testing for six antimicrobial agents were compared. RESULTS: The resistance rates of H. pylori to clarithromycin and dual resistance to clarithromycin and metronidazole were found significantly higher during the late period. Multivariable analysis showed that the later period, older age, and diabetes mellitus were independent predictors for antimicrobial resistance. CONCLUSIONS: Our study has shown that there is an increasing resistance of H. pylori to clarithromycin and metronidazole while its susceptibility is unaffected with time to other antibiotics. More recent cross-sectional studies with larger samples are warranted in order to evaluate the changes in the resistance patterns of H. pylori to various antibiotics with time.

Ethical Considerations Within the ESPGHAN Community.

There are limited data on ethical issues related to the daily practice of members of the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). The role of the ESPGHAN Ethics Committee (EC) is to provide advice on such matters to its members. The present survey aimed to evaluate the current function, and reasons that ESPGHAN members consulted the ECs. One hundred and five participants from 24 different countries answered the questionnaire. Thirty-five point seven percent of the participants used the ESGHAN EC to ask about clinical practice problems and patient-related issues whereas 21.4% ask about human research questions. An important additional finding was that 66.3% of respondents consulted their hospital's EC when they had ethical concerns and 17.4% consulted with other colleagues with expertise. This is the first survey in the ESPGHAN and Europe that analyses ethical issues that are important to members of the National Societies for Pediatric Gastroenterology Hepatology and Nutrition.

High Metronidazole and Clarithromycin Resistance of Helicobacter Pylori Isolated from Previously Treated and Naïve Patients.

BACKGROUND: Antimicrobial resistance is the main determinant for Helicobacter pylori treatment failure. Regional antimicrobial susceptibility testing is essential for appropriate antibiotic selection to achieve high eradication rates. OBJECTIVES: To assess primary and secondary H. pylori resistance in isolates recovered from Israeli naïve and treatment failures. To identify predictors of resistance. METHODS: In this retrospective study, in vitro activity of isolated H. pylori in Israel was tested against metronidazole, clarithromycin, tetracycline, amoxicillin, and levofloxacin in 128 isolates: 106 from treatment failures and 22 from naïve untreated patients. The minimal inhibitory concentration values were determined according to the Etest instructions. Treatment failures previously failed at least one treatment regimen. RESULTS: No resistance to amoxicillin and tetracycline was detected. Resistance to metronidazole and clarithromycin was high in H. pylori isolates both from treated and untreated patients: 68.9%, 68.2% for metronidazole (P = 0.95); 53.8%, 59.1% for clarithromycin (P = 0.64), respectively. Dual resistance to clarithromycin and metronidazole was seen in 45.3% and 50%, respectively (P = 0.68). Resistance to levofloxacin was detected in two (1.9%) isolates from treated patients. Simultaneous resistance to clarithromycin, metronidazole, and levofloxacin was seen in an isolate from a treated patient. Age was the only predictor of resistance to metronidazole and clarithromycin. CONCLUSIONS: The resistance rates to both single and dual metronidazole and clarithromycin in isolates recovered from both Israeli naïve and treated patients is high. Low resistance renders levofloxacin an attractive option for second or third line treatment. Therapeutic outcome would benefit from susceptibility testing after treatment failure.

The Association of Helicobacter pylori Seropositivity with All-Cause Mortality among Colorectal Cancer Patients Undergoing PET/CT Scans.

BACKGROUND: Evidence has been emerging that Helicobacter pylori may also impact colorectal cancer (CRC). Positron emission tomography/computed tomography (PET/CT) imaging can predict overall survival in CRC patients. OBJECTIVES: To determine a possible association between H. pylori seropositivity and all-cause mortality among CRC patients evaluated by PET/CT scans. METHODS: This prospective cohort study was comprised of 110 consecutive CRC patients who had undergone a PET/CT evaluation in a tertiary academic medical center. Data included demographics, body mass index (BMI), tumor node metastasis stage at diagnosis, treatment, time from diagnosis to PET/CT, and PET/CT findings. All patients were tested for anti-H. pylori immunoglobulin G (IgG) antibodies and followed for 36 months from the day of the PET/CT scan. Mortality was documented. Univariate and multivariate Cox regression was used to estimate the hazard ratio (HR) of H. pylori serological status. RESULTS: During the follow-up period, of the 110 CRC patients 41 (37.3%) died and 69 (62.7%) survived. Of the 41 patients, 26 (63.4%) were H. pylori seropositive and 15 (36.6%) were seronegative. Multivariate analysis showed that H. pylori seropositivity was associated with increased mortality (HR 3.46, 95% confidence interval 1.63-7.32), stage IV at diagnosis, metastatic disease found on PET/CT, longer time from diagnosis to PET/CT, lower BMI, and older age. CONCLUSIONS: Our findings suggest that H. pylori infection may be a risk factor for all-cause mortality among CRC patients who are evaluated by PET/CT. Multicenter studies with larger patient groups are needed to confirm our findings.

Primary and Secondary Antibiotic Resistance of Helicobacter pylori in Israeli Children and Adolescents.

BACKGROUND: Empiric treatment for Helicobacter pylori is influenced by antibiotic susceptibility of infecting strains. A rise in the resistance rate to clarithromycin and metronidazole has been reported in pediatric populations. OBJECTIVES: To assess the primary and secondary antibiotic resistance of H. pylori isolates in Israeli children and adolescents. METHODS: A retrospective review of H. pylori isolates cultured from antral biopsies of consecutive children aged 1 to 18 years, who were referred to the Pediatric Gastroenterology Unit, Kaplan Medical Center, over a 2.8 year period, was performed. Antibiotic susceptibility to clarithromycin, metronidazole, amoxicillin, tetracycline, and levofloxacin was determined by E-test. Data on the age of the patient, indication for endoscopy, and antibiotic treatment for H. pylori in previously treated children was collected. RESULTS: Cultures for H. pylori yielded 123 isolates. In children not previously treated (n=95), the primary global resistance was 38% with resistance to clarithromycin 9.5%, metronidazole 32.6 %, and to both 4.2%. Respective rates of resistance in previously treated children (n=28) were 71% (P = 0.002), 29% (P = 0.02), and 61% (P = 0.007). Simultaneous resistance to both drugs was found in 18% (P = 0.02). All H. pylori strains were susceptible to amoxicillin, tetracycline, and levofloxacin. Past eradication treatment was the only independent risk factor for antibiotic resistance in multivariate analysis. CONCLUSIONS: Significantly higher resistance rates were found in previously treated patients, stressing the need to refrain from empiric treatment using the "test and treat strategy." Culture-based treatment strategy should be considered in all previously treated children.

Non-pharmacological treatment of Helicobacter pylori.

Many food and plant extracts have shown in vitro anti-Helicobacter pylori (H. pylori) activity, but are less effective in vivo. The anti-H. pylori effects of these extracts are mainly permeabilitization of the membrane, anti-adhesion, inhibition of bacterial enzymes and bacterial grown. We, herein, review treatment effects of cranberry, garlic, curcumin, ginger and pistacia gum against H. pylori in both in vitro, animal studies and in vivo studies.

Helicobacter pylori: friend or foe?

Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is "anyone with a fear of gastric cancer" which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection.

Association of Helicobacter pylori with coronary artery disease and myocardial infarction assessed by myocardial perfusion imaging.

BACKGROUND: The relationship between Helicobacter pylori infection and coronary artery disease (CAD) has as yet not been fully examined. The myocardial perfusion imaging (MPI) stress test has proven its efficacy as an integral part of diagnosing CAD. OBJECTIVES: To investigate the association between CAD and H. pylori infection using MPI. METHODS: This prospective study evaluated CAD positivity among consecutive patients referred to a tertiary medical center for a stress/rest MPI. All patients were tested for serum anti-H. pylori and CagA protein immunoglobulin G antibodies. The CAD positivity group included patients with ischemia and/or myocardial infarction (MA) on a stress MPI, coronary artery bypass graft surgery (CABG), or percutaneous coronary interventions (PCI). CAD-negative subjects were defined as participants with a normal MPI, no pathological Q waves in resting ECG tracing, and no history of CAD. Both groups were compared for H. pylori and CagA seropositivity. Patients' demographic data, risk factors for CAD, and childhood socioeconomic status were recorded. RESULTS: The study group consisted of 300 consecutive patients, 170 men and 130 women; 64% (110/173) CAD-positive patients and 47% (60/127) CAD-negative participants were found seropositive for H. pylori infection (P = 0.005). In the adjusted analysis, H. pylori infection was found to be associated with CAD positivity (odds ratio 1.83, 95% confidence interval 1.06-3.17, P = 0.031), and MI (fixed perfusion defects on MPI) (OR 3.36, 95% CI 1.44-7.84, P = 0.005). No association was noted with CagA positivity. CONCLUSIONS: In patients undergoing a stress MPI, serum anti-H. pylori antibodies positivity was found to be associated with CAD, independent of traditional cardiovascular risk factors.

Helicobacter pylori infection is associated with advanced colorectal neoplasia.

OBJECTIVE: The aim of this article was to evaluate the prevalence of Helicobacter pylori infection in patients diagnosed with advanced colorectal neoplasia undergoing a colonoscopy compared to patients without neoplasia. MATERIAL AND METHODS: This cross-sectional study investigated the association of neoplastic lesions diagnosed on colonoscopy with H. pylori infection in a consecutive series of subjects who had undergone a pancolonoscopy in a single academic medical center. All patients were tested by ELISA and the immunoblot technique for serum anti-H. pylori and CagA protein IgG antibodies. Multivariate analyses were adjusted for potential-relevant confounders, including age, sex, smoking, childhood socioeconomic status, and family history of colorectal cancer. RESULTS: Two hundred and seventy-three patients were included in the study: 75% (84/112), diagnosed with neoplastic colorectal lesions and 48% (77/161) without neoplastic lesions, were found to be seropositive for H. pylori infection (p < 0.001). H. pylori infection was found in 66/77 (86 %) patients with advanced neoplasia, 18/35 (51%) patients with nonadvanced neoplasia, and 48% (77/161) patients without neoplasia (p < 0.001). In the adjusted analysis, H. pylori infection was found to be associated with advanced colorectal neoplasia (odds ratio, OR 9.57; 95% CI 4.31-21.2; p < 0.001) and CRC (OR 7.98;95% CI 3.16-20.16; p < 0.001). There was no association in patients who were CagA positive. CONCLUSION: H. pylori infection is associated with the development of advanced colorectal neoplasia. More studies are needed to confirm our findings.

Neurologic presentation in children with ataxia-telangiectasia: is small head circumference a hallmark of the disease?

OBJECTIVE: To define the neurologic characteristics and course of ataxia-telangiectasia (A-T). STUDY DESIGN: Retrospective cross-sectional chart study of 57 children (ages 2 to 19 years) followed at an A-T clinic. Cerebellar and extracerebellar symptoms were graded according to degree of functional impairment. Head circumferences were plotted from the charts and z-scores were calculated and compared with that of family members. RESULTS: Ataxia was present in 87.7%, followed by dysarthria (82.1%), dysmetria (75.4%), bradykinesia (69.2%), hyperkinetic movements (58.9%), and dystonia (15.8%). All features aggravated with age. The most striking clinical observation in our patients was low head circumference (z-score below 1), which was present in 60.9%; 17% had true microcephaly (z-score below 2). Microcephaly appeared postnatally, was proportionate to height and weight, and did not correlate with severity of ataxia or genotype. CONCLUSIONS: In addition to cerebellar ataxia, extrapyramidal symptoms, especially bradykinesia, were frequent and disabling. Microcephaly is an integral part of A-T; understanding its pathogenesis may shed light on the mechanism by which ATM mutation causes dysfunction in the nervous system.

Antibiotic resistance of Helicobacter pylori in Israeli children.

OBJECTIVES: To determine the antibiotic susceptibility of Helicobacter pylori isolates from Israeli children; assess the role of previous antibiotic use in the development of antibiotic resistance and examine the possibility of simultaneous colonization of strains with different resistance patterns in the same patients. MATERIAL AND METHODS: A prospective case-series design was used. The study group included 174 patients aged 1-18 years referred to the Schneider Children's Medical Center of Israel for gastroscopy over a 2.5-year period. Antibiotic susceptibility to amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin was determined by E-test on gastric biopsies (2 per patient). Clinical and demographic data were obtained by questionnaire. RESULTS: Cultures for H. pylori yielded 55 isolates from 53 children. In treatment-naïve children, the prevalence rate of primary resistance to clarithromycin was 25% and to metronidazole, 19%. Respective rates in children previously treated for H. pylori infection were 42% (p = 0.22) and 52% (p = 0.016). Simultaneous resistance to both drugs was found in 13% of isolates (n = 7), all from children with previous treatment failure. No resistance was found to amoxicillin, tetracycline or levofloxacin. Clarithromycin resistance was associated with macrolide use for any indication during the previous year (p = 0.033). In 2 patients (3.8%), a different H. pylori strain was cultured from each biopsy. CONCLUSIONS: H. pylori resistance to clarithromycin and metronidazole is high in Israeli children, particularly in those previously treated for H. pylori infection, in whom culture-based treatment should be considered. The simultaneous colonization of multiple strains in a minority of patients needs to be further characterized.

Effect of cranberry juice on eradication of Helicobacter pylori in patients treated with antibiotics and a proton pump inhibitor.

Cranberry constituents are known to exert anti-adhesion activity on H. pylori in vitro. To determine their possible additive effect to triple therapy with omeprazole, amoxicillin and clarithromycin (OAC), a double-blind randomized clinical study was carried out. One-hundred-seventy-seven patients with H. pylori infection treated with OAC for 1 week were randomly allocated to receive 250 mL of either cranberry juice (cranberry-OAC, n = 89) or placebo beverage (placebo-OAC, n = 88) twice daily and only cranberry juice or placebo beverage for the next 2 weeks. Treatment outcome was determined with the(13)C urea breath test ((13)C-UBT). An additional control group consisted of patients referred to the same center during the same period who were treated with OAC alone for 1 week (non-placebo-OAC, n = 712). Overall, the rate of H. pylori eradication ((13)C-UBT < 3.5) was 82.5%, with no statistically significant difference among the three arms. Analysis by gender revealed that for female subjects, the eradication rate was higher in the cranberry-OAC arm (n = 42, 95.2%) than in the placebo-OAC arm (n = 53, 86.8%) and significantly higher than in the non-placebo-OAC group (n = 425, 80%; p = 0.03). For males, the rate was nonsignificantly lower in the cranberry-OAC arm (n = 35, 73.9%) than in the placebo-OAC arm (n = 45, 80.0%) and non-placebo-OAC group (n = 287, 85.0%). These results suggest that the addition of cranberry to triple therapy improves the rate of H. pylori eradication in females.

Elevated 13C urea breath test values females infected with Helicobacter pylori.

(13)C-urea breath test (UBT) for the diagnosis of Helicobacter pylori requires a high density and active bacteria and has the potential to provide a noninvasive index of bacterial growth. We describe the gender differences in delta over baseline (13)C-UBT values in 7373 patients (4531 females and 2842 males) who underwent (13)C-UBT test for the diagnosis of H. pylori infection. A significantly (P<.001) higher mean +/- SD excess delta (13)CO(2) excretion was recorded in females (24.7+/-17.4) compared to males (17.6+/-11.8) aged 10-80 years. The age-adjusted difference between sexes was 7.1 (95% confidence interval, 6.4-7.9). Our analysis demonstrates quantitatively for the first time gender associated differences in H. pylori host interaction. This study suggests that infected females have a higher bacterial load and therefore may potentially infect their children at a higher degree than males.

Susceptibility-guided vs. empiric retreatment of Helicobacter pylori infection after treatment failure.

Successful eradication of Helicobacter pylori after failure of standard triple therapy is difficult because of the higher resistance to metronidazole and clarithromycin. We evaluated the efficacy of susceptibility-guided vs. empiric retreatment for H. pylori after at least one treatment failure and determined the prevalence of posttreatment antibiotic resistance. Forty-nine patients in whom at least one treatment regimen for H. pylori eradication had failed underwent gastric biopsy and culture and were retreated according to the in vitro susceptibility results. Findings were compared with those for 49 control patients referred to our center for a (13)C-urea breath test. H. pylori eradication was assessed by urea breath test at least 6 weeks after retreatment in both groups. Susceptibility-guided retreatment was associated with better eradication rates than empiric treatment. The difference remained significant in stratified and multivariate analysis. Susceptibility-guided retreatment appears to be significantly more effective than empiric retreatment in eradicating H. pylori after at least one previous treatment failure.

Helicobacter pylori and Clostridium difficile in cystic fibrosis patients.

We describe the prevalence of H. pylori and toxigenic Clostridium difficile (CD) infection and its relationship with gastrointestinal symptoms and pancreatic sufficiency (PS) or insufficiency (PI) in cystic fibrosis (CF) patients. Stool specimens from 30 consecutive patients with CF, aged 1-44, and from 30 healthy similarly aged subjects were tested for the H. pylori antigen by specific monoclonal antibodies and for CD toxins by Tox A/B assay and Tox A assay. CF patients were assessed clinically and tested for specific H. pylori serum antibodies and for mutations. In CF patients, the prevalence of H. pylori antigen was 16.6% (5/30), compared to 30% (9/30) in controls. Of the 26 CF patients with PI, only 2 (7.6%) were infected by H. pylori, compared with 3 of the 4 (75%) patients with PS (P=0.001). H. pylori infection was diagnosed in 3 of 5 (60%) CF patients carrying mild mutations, compared to 1 of 25 (4%) CF patients carrying severe mutations (P=0.01). Fourteen of 30 (46.6%) stool specimens from CF patients tested positive in the ToxA/B assay, and 3 of 14 tested positive for ToxA. No significant differences in antibiotic use, severity of lung disease, PI, chronic abdominal pain, or genotype were found between the two groups. None of the controls was positive for CD toxins. Prevalence of H. pylori infection in CF patients was lower than in similarly aged non-CF controls. CF patients with PI or a history of distal intestinal obstruction syndrome and those carrying mutations associated with a severe phenotype were protected against H. pylori infection. Almost half of the CF patients were asymptomatic carriers of CD producing mostly toxin B. More studies are needed to confirm our results in a larger group of CF patients.

In vitro activity of levofloxacin against Helicobacter pylori isolates from patients after treatment failure.

We tested the in vitro activity of levofloxacin (LEV), amoxicillin (AMP), clarithromycin (CLA), metronidazole (MET), and tetracycline (TET) against 70 clinical isolates of Helicobacter pylori recovered from 70 dyspeptic patients. All patients had previously failed 2 treatment regimens: first-line triple therapy with omeprazole, AMP, and CLA, and second-line quadruple therapy with omeprazole, MET, TET, and bismuth. Resistance to CLA, MET, and LEV was found in 65.7%, 57.1%, and 18.6% of isolates, respectively. Resistance to both CLA and MET was found in 32.8%, and to CLA, MET, and LEV in 12.8%. Only 4 of the isolates were resistant to both CLA and LEV, and none was resistant to LEV alone or to MET and LEV. Physicians should consider triple therapy with omeprazole, LEV, and AMP in patients unsuccessfully treated with first- and second-line regimens.

Helicobacter pylori infection in pediatrics.

The diagnosis of Helicobacter pylori infection continues to challenge practicing physicians around the world. In the last year, several reports from Africa tried to examine the epidemiology of H. pylori infection in nursing babies, while others investigated the association between recurrent abdominal pain symptoms and H. pylori. In the diagnostic arena, attempts were made to improve diagnostic accuracy, mainly by using a new monoclonal version of the stool antigen test, and by applying the urea breath test in smaller children. In the current report, the most important studies on H. pylori infection in children published in the last year are also reviewed.

Association of CagA+ Helicobacter pylori infection with aortic atheroma.

BACKGROUND: To investigate possible association between infection with CagA(+) strains of Helicobacter pylori and aortic atheroma diagnosed by transesophageal echocardiography. METHODS AND RESULTS: One hundred and eighty-eight consecutive subjects prospectively examined for presence of aortic atheroma (localized intimal thickening of >/=3mm) by transesophageal echocardiography were tested for serum IgG antibodies against H. pylori (enzyme-linked immunosorbent assay) and CagA protein (Western blot assay). The association between infection with H. pylori, CagA status of the infecting H. pylori strains, and aortic atherosclerosis was evaluated after adjusting for coronary artery disease risk factors. There was a linear trend for presence of atheroma in subjects with CagA-positive H. pylori infection (51/81, 63%) compared to subjects with CagA-negative H. pylori infection (21/45, 46.7%) and uninfected subjects (18/62, 29%) (p=0.003). H. pylori seropositivity was not associated with aortic atheroma (OR 2.9; 95% CI, 0.8-10.3; p=0.11) when CagA status is not taken into account. On multivariate analysis, parameters associated with risk of aortic atheroma were CagA-positive H. pylori seropositivity (OR 4.4; 95% CI, 1.4-14.7; p=0.01), older age (OR 1.2; 95% CI, 0.9-14.7; p=0.01), having ever smoked cigarettes (OR 3.6; 95% CI, 1.3-10.0; p<0.001), and elevated serum triglyceride level (OR 3.4; 95% CI, 1.3-9.4; p=0.02). CONCLUSIONS: After controlling for H. pylori infection and coronary artery disease risk factors, infection with a CagA-positive strain of H. pylori was independently associated with aortic atherosclerosis. This study suggests a gradient of atherosclerosis between uninfected individuals and patients with CagA-positive H. pylori infection and should prompt research into the role of CagA-positive H. pylori infection in the inflammatory atherosclerotic process.