Antibiotic resistance patterns of Helicobacter pylori in North Israel - A six-year study.

BACKGROUND: One main challenge in Helicobacter pylori (H. pylori) eradication is its increasing antibiotic resistance. Additionally, resistance rates vary between geographic areas and periods. However, data are limited since susceptibility testing is not routinely performed. Thus, it is valuable to gather data regarding H. pylori's resistance rates in Israel that would aid in better adjustment of treatment. MATERIALS AND METHODS: The study included 540 H. pylori isolates, recovered from gastric biopsy samples of patients who had undergone endoscopy, during 2015-2020, at the Padeh Poriya Medical Center. Antibiotic susceptibility testing to amoxicillin, clarithromycin, metronidazole, levofloxacin, rifampicin, and tetracycline was performed using the Etest technique. Data regarding participants' sex, age, and ethnic group were collected. For every antibiotic and for multi-resistance, generalized linear models were used to estimate crude and adjusted estimated differences in mean MIC and odds ratios (ORs) for every year, compared with the reference year 2015. RESULTS: The highest resistance rates were for clarithromycin and metronidazole (46.3% and 16.3%, respectively). Patients above 18 had higher resistance rate to rifampicin and multi-resistance (3.3% and 14.8%), compared with patients under 18 (0.5% and 8.4%, respectively). Resistance rates for levofloxacin, rifampicin, and multi-resistance were significantly higher among Arab patients, compared with Jewish patients. During the 6-year surveillance, a significant annual trend in MIC for metronidazole and in ORs for metronidazole, levofloxacin, and multi-resistance were observed (after adjustment). During 2020 compared with 2015, significant increased ORs were observed for levofloxacin and metronidazole [5.72 (1.03-31.84); 4.28 (1.30-14.14), respectively]. CONCLUSIONS: In light of the remarkable changes in antibiotic resistance of H. pylori during the study's period and the increasing resistance rates to various antibiotics, it is very important to continuously monitor H. pylori antibiotic susceptibly. In order to increase eradication rates of this bacterium, therapy regimes must be based on an updated antibiotic resistance data.

Monitoring Enables Progress: A Nationwide Quality Improvement Program in Children With Crohn Disease.

OBJECTIVES: In this quality improvement program, named quality in pediatric inflammatory bowel disease, we constructed a nation-wide platform that prospectively recorded clinically important quality indicators in pediatric inflammatory bowel diseases (PIBD), aiming at improving clinical management across the country. METHODS: Representatives of all 21 PIBD facilities in Israel formed a Delphi group to select quality indicators (process and outcomes), recorded prospectively over 2 years in children with Crohn's disease 2-18 years of age seen in the outpatient clinics. Monthly anonymized reports were distributed to all centers, allowing comparison and improvement. Trends were analyzed using the Mann-Kendall test, reporting τ (tau) values. RESULTS: The indicators of 3254 visits from 1709 patients were recorded from September 2017 to September 2019 (mean age 14.7 ±â€Š3.1 years, median disease duration 1.8 years (interquartile range 0.69-4.02)). An increase in three of five process indicators was demonstrated: obtaining drug levels of anti-tumor necrosis factor (TNF) (τ = 0.4; P = 0.005), utilization of fecal calprotectin (τ = 0.38; P = 0.008) and bone density testing (τ = 0.45; P = 0.002). Among outcome indicators, three of nine improved as measured during the preceding year: calprotectin <300 µg/mg (τ = 0.35; P = 0.015), and "resolution of inflammation" defined as a composite of endoscopy, imaging and fecal calprotectin (τ = 0.39; P = 0.007). Endoscopic healing reached borderline significance (τ = 0.28; P = 0.055). An increase in the use of biologics throughout the study was observed (τ = 0.47; P = 0.001) with a concurrent decrease in the use of immunomodulators (τ = -0.47; P = 0.001). CONCLUSIONS: Quality improvement nationwide programs can be implemented with limited resources while facilitating standardization of care, and may be associated with improvements in measured indicators.

Dietary Therapies Induce Rapid Response and Remission in Pediatric Patients With Active Crohn's Disease.

BACKGROUND & AIMS: Dietary therapies based on exclusion of usual dietary elements induce remission in children with Crohn's disease (CD), whereas re-exposure induces rebound inflammation. We investigated whether a short trial of dietary therapy, to identify patients with and without a rapid response or remission on the diet (DiRe), can be used to predict success or failure of long-term dietary therapy. METHODS: We collected data from the multicenter randomized trial of the CD exclusion diet (CDED). We analyzed data from 73 children with mild to moderate CD (mean age, 14.2 ± 2.7 y) randomly assigned to groups given either exclusive enteral nutrition (EEN, n = 34) or the CDED with 50% (partial) enteral nutrition (n = 39). Patients were examined at baseline and at weeks 3 and 6 of the diet. Remission was defined as CD activity index scores below 10 and response was defined as a decrease in score of 12.5 points or clinical remission. Inflammation was assessed by measurement of C-reactive protein. RESULTS: At week 3 of the diet, 82% of patients in the CDED group and 85% of patients in the EEN group had a DiRe. Median serum levels of C-reactive protein had decreased from 24 mg/L at baseline to 5.0 mg/L at week 3 (P < .001). Among the 49 patients in remission at week 6, 46 patients (94%) had a DiRe and 81% were in clinical remission by week 3. In multivariable analysis, remission at week 3 increased odds of remission by week 6 (odds ratio, 6.37; 95% CI, 1.6-25; P = .008) whereas poor compliance reduced odds of remission at week 6 (odds ratio, 0.75; 95% CI, 0.012-0.46; P = .006). CONCLUSIONS: For pediatric patients with active CD, dietary therapies (CDED and EEN) induce a rapid clinical response (by week 3). Identification of patients with and without a rapid response to diet might help identify those who, with compliance, will be in clinical remission by week 6 of the diet. ClinicalTrials.gov no: NCT01728870.

Crohn's Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial.

BACKGROUND & AIMS: Exclusive enteral nutrition (EEN) is recommended for children with mild to moderate Crohn's disease (CD), but implementation is challenging. We compared EEN with the CD exclusion diet (CDED), a whole-food diet coupled with partial enteral nutrition (PEN), designed to reduce exposure to dietary components that have adverse effects on the microbiome and intestinal barrier. METHODS: We performed a 12-week prospective trial of children with mild to moderate CD. The children were randomly assigned to a group that received CDED plus 50% of calories from formula (Modulen, Nestlé) for 6 weeks (stage 1) followed by CDED with 25% PEN from weeks 7 to 12 (stage 2) (n = 40, group 1) or a group that received EEN for 6 weeks followed by a free diet with 25% PEN from weeks 7 to 12 (n = 38, group 2). Patients were evaluated at baseline and weeks 3, 6, and 12 and laboratory tests were performed; 16S ribosomal RNA gene (V4V5) sequencing was performed on stool samples. The primary endpoint was dietary tolerance. Secondary endpoints were intention to treat (ITT) remission at week 6 (pediatric CD activity index score below 10) and corticosteroid-free ITT sustained remission at week 12. RESULTS: Four patients withdrew from the study because of intolerance by 48 hours, 74 patients (mean age 14.2 ± 2.7 years) were included for remission analysis. The combination of CDED and PEN was tolerated in 39 children (97.5%), whereas EEN was tolerated by 28 children (73.6%) (P = .002; odds ratio for tolerance of CDED and PEN, 13.92; 95% confidence interval [CI] 1.68-115.14). At week 6, 30 (75%) of 40 children given CDED plus PEN were in corticosteroid-free remission vs 20 (59%) of 34 children given EEN (P = .38). At week 12, 28 (75.6%) of 37 children given CDED plus PEN were in corticosteroid-free remission compared with 14 (45.1%) of 31 children given EEN and then PEN (P = .01; odds ratio for remission in children given CDED and PEN, 3.77; CI 1.34-10.59). In children given CDED plus PEN, corticosteroid-free remission was associated with sustained reductions in inflammation (based on serum level of C-reactive protein and fecal level of calprotectin) and fecal Proteobacteria. CONCLUSION: CDED plus PEN was better tolerated than EEN in children with mild to moderate CD. Both diets were effective in inducing remission by week 6. The combination CDED plus PEN induced sustained remission in a significantly higher proportion of patients than EEN, and produced changes in the fecal microbiome associated with remission. These data support use of CDED plus PEN to induce remission in children with CD. Clinicaltrials.gov no: NCT01728870.

Antimicrobial susceptibility of Helicobacter pylori strains isolated from children in Israel.

OBJECTIVES: Helicobacter pylori is a bacterial pathogen causing inflammation of the gastric mucosa that may lead to peptic ulcer, perforation or malignancy. Children are at risk of contracting H. pylori and developing subsequent morbidity. Diagnosis and management in children are difficult and merit a different approach compared with adults. This study aimed to describe the antimicrobial resistance rates of H. pylori to amoxicillin, tetracycline, clarithromycin, metronidazole, levofloxacin and rifampicin. METHODS: Biopsies (n=154) collected during endoscopic examinations were cultivated for 10days using a growth medium selective for H. pylori, of which 89 were H. pylori-positive. Antimicrobial resistance of the strains was assessed by Etest to establish minimum inhibitory concentrations (MICs) according to British Society for Antimicrobial Chemotherapy guidelines. RESULTS: Resistance rates were most notable for amoxicillin and clarithromycin at 12% and 35% with MICs of 0.74µg/mL and 2.51µg/mL, respectively. Resistance rates to tetracycline and levofloxacin were 8% and 2% with MICs of 2.57µg/mL and 2.0µg/mL, respectively. Resistance rates to rifampicin and metronidazole were 3% and 8% with MICs of 2.0µg/mL and 9.71µg/mL, respectively. CONCLUSION: Current rising antibiotic resistance rates for H. pylori are of concern. Performance of culture enables determination of the susceptibility profile, which may lead to a better choice of, and perhaps narrower spectrum, antibiotic agent. In light of these findings, we suggest that optimising the choice of antibiotic agent in children with H. pylori infection remains a challenge for clinicians and thus requires further investigation in randomised clinical trials.

GenoType® HelicoDR test in comparison with histology and culture for Helicobacter pylori detection and identification of resistance mutations to clarithromycin and fluoroquinolones.

BACKGROUND: There are several methods for Helicobacter pylori infection diagnosis. AIM: The efficacies of three methods for H. pylori identification directly from a biopsy were compared: histology, culture, and molecular GenoType® HelicoDR test. MATERIALS & METHODS: Eighty-five triplicates of stomach antrum biopsies were obtained during gastroscopy procedures for culture, histology, and molecular assay. In addition, we performed molecular identification of genes encoding resistance to clarithromycin and fluoroquinolones. RESULTS: The results have shown that the most specific method with the highest number of positive specimens was by molecular kit, compared to culture and histology (94.3%, 77.1%, and 71.4%, respectively). There was a higher rate of resistance mutations to clarithromycin than to fluoroquinolones (68.26% vs 20%). The most common mutations for clarithromycin and fluoroquinolones resistance were found in alleles A2143G and N87K, respectively. The highest rate of positive specimens was identified by the molecular. DISCUSSION: GenoType HelicoDR kit (94.3%), which has several advantages: direct identification, strain resistance characterization, mixture of genotypes detection, and no transport or storage limitations; thus, it is an excellent epidemiological screening tool. This work has demonstrated a lower resistance rate to fluoroquinolones; it is possible that in the investigated geographic area treatment with fluoroquinolones may be preferable to clarithromycin. GenoType® HelicoDR test eliminates the need for culture performance and susceptibility tests for several common antibiotic agents and enables optimal and specific antibiotic treatment adjustment. CONCLUSION: We recommend a combination of PCR assay and bacterial culture for a quick method of screening and more efficient identification of H. pylori strains and resistance patterns.

Improvement and optimization of the classical gastric biopsy culture technique for Helicobacter pylori diagnosis using trypsin.

Helicobacter pylori infection represents a key factor in the aetiology of various gastrointestinal diseases. H. pylori infection diagnosis is generally achieved using both invasive (e.g. biopsy of the gastric epithelium) and non-invasive methods. Therefore, cultivation on a growth medium becomes complex. Trypsin is a proteinase enzyme that plays a role in an early stage of tissue digestion. In this study, we used trypsin in order to improve the diagnostic sensitivity of the H. pylori cultivation technique. We used 46 duplicate antrum biopsy specimens, divided into trypsin-treated and non-treated groups. The tissues were seeded on a selective H. pylori growth agar medium. We demonstrated that the classic H. pylori culture technique misses the growth of a large number of H. pylori colonies. Significantly more colonies were found in the trypsin-treated specimens group.

An efficiency comparison between three invasive methods for the diagnosis of Helicobacter pylori infections: Culture from stomach biopsy, rapid urease test (CUTest(®)), and histologic examination of gastric biopsy.

BACKGROUND: Helicobacter pylori is one of the most prevalent pathogenic bacteria in the world, and humans are its principal reservoir. There are several available methods to diagnose H. pylori infection. Disagreement exists as to the best and most efficient method for diagnosis. METHODS: In this paper, we report the results of a comparison between three invasive methods for H. pylori diagnosis among 193 patients: culture, biopsy for histologic examination, and rapid urease test (CUTest(®)). RESULTS: We found that all three methods have a high sensitivity and specificity for the diagnosis of infections caused by H. pylori. However, the culture method, which is not used routinely, also showed high sensitivity, probably due to biopsies' seeding within 30 minutes, using warm culture media, non-selective media, and longer incubation. CONCLUSIONS: Although not a routine test, culture from biopsy can be meaningful in identification of antibiotic-resistant strains of H. pylori and should therefore be considered a useful diagnostic tool.

Susceptibility of Helicobacter pylori to Levofloxacin and Rifampicin in Israel.

The aim of this study was to assess the resistance level of Helicobacter pylori to levofloxacin and rifampicin from samples collected from pediatric and adult Israeli patients from 2012 to 2013. A total of 117 isolate samples of H. pylori were collected between 2012 and 2013. Isolates were cultured from stomach antrum biopsies and identified by the microbiology laboratory. Isolates were considered susceptible to levofloxacin and rifampicin by an Etest. Out of 117 isolates, 105 were found susceptible and 12 resistant to levofloxacin. For rifampicin, 104 isolates were susceptible and 13 were resistant. Study results estimate an alarming resistance rate, which reiterates the need for prudent use of alternative antibiotics to prevent further spread of resistant strains. Therefore, we suggest subjecting cultures from biopsy samples to susceptibility testing for the purpose of identification of strains resistant to levofloxacin and rifampicin among other antibiotic agents. This will allow for successful monitoring of microbial resistance and will assure prudent use of antimicrobial modalities.

Comparison of two dosing methods for induction of response and remission with oral budesonide in active pediatric Crohn's disease: a randomized placebo-controlled trial.

BACKGROUND: Oral budesonide has been found to be comparable to systemic corticosteroids in mild to moderately active Crohn's disease (CD). Remission rates in pediatric studies to date have been suboptimal (47%-55%), even though patients with colonic involvement were excluded in some studies. In addition, the optimal pediatric dosing regimen has never been evaluated before. METHODS: This was a randomized, controlled, double-blind study in 70 children with mild or moderately active CD randomized to 1 of 2 groups: Group 1: Standard dose budesonide (9 mg/day) for 7 weeks followed by 6 mg budesonide daily for an additional 3 weeks. Group 2: Induction with 12 mg/day for the first month followed by the same regimen as Group 1. Outcome measures included a decrease in Pediatric Crohn's Disease Activity Index and remission rates. Patients with colonic disease were not excluded. RESULTS: At week 7 a clinical response was obtained in 51.4% in Group 1 versus 74.3% in Group 2. A significant decrease in C-reactive protein was seen only in Group 2. At the end of treatment, remission was obtained in 42.9% in Group 1 versus 65.7% in Group 2 (P = 0.054). There was no significant difference in adverse events or serum cortisol. CONCLUSIONS: Use of an induction dose of budesonide followed by a budesonide taper resulted in a trend to higher rates of clinical remission and a decrease in inflammation, without an increase in steroid-associated side effects. Budesonide was also useful for patients with ileocolonic disease.

A comparison of budesonide and prednisone for the treatment of active pediatric Crohn disease.

OBJECTIVES: Budesonide has been found effective in patients with mild and moderate Crohn disease and has been found to cause fewer side effects than prednisone. The use of oral budesonide has not been prospectively evaluated in children with Crohn disease. Therefore, the authors initiated a trial to compare remission and tolerance to budesonide and prednisone in children with mild or moderately active Crohn disease. METHODS: A prospective randomized open controlled 12-week trial was carried out comparing pH modified release budesonide, 9 mg, versus prednisone, 40 mg, in children with active mild to moderate pediatric Crohn disease. RESULTS: Thirty-three patients (20 boys and 13 girls; mean age, 14.3 years) enrolled and completed the study. The groups treated with budesonide and prednisone did not differ by age, onset of disease, location of disease, or disease activity. The remission rate at 12 weeks was 47% in the budesonide treatment group and 50% in the prednisone treatment group. Side effects occurred in 32% and 71% of patients treated with budesonide and prednisone, respectively (P< 0.05). Severity of cosmetic side effects was significantly lower in patients treated with budesonide (P< 0.01). CONCLUSIONS: Remission rates for Crohn disease with budesonide and prednisone treatment in this study were similar. Pediatric patients treated with budesonide had significantly fewer side effects than patients treated with prednisone. Budesonide should be considered an alternative to prednisone in pediatric patients with mild to moderate disease activity.