Patrick Bontems

Prospective multicentre study on antibiotic resistance of Helicobacter pylori strains obtained from children living in Europe

Aim: To prospectively assess the antibacterial resistance rate in Helicobacter pylori strains obtained from symptomatic children in Europe. Methods: During a 4-year period, 17 paediatric centres from 14 European countries reported prospectively on patients infected with H pylori, for whom antibiotic susceptibility was tested. Results: A total of 1233 patients were reported from Northern (3%), Western (70%), Eastern (9%) and Southern Europe (18%); 41% originated from outside Europe as indicated by mother’s birth-country; 13% were <6 years of age, 43% 6–11 years of age and 44% >11 years of age. Testing was carried out before the first treatment (group A, n = 1037), and after treatment failure (group B, n = 196). Overall resistance to clarithromycin was detected in 24% (mean, A: 20%, B: 42%). The primary clarithromycin resistance rate was higher in boys (odds ratio (OR) 1.58; 1.12 to 2.24, p = 0.01), in children <6 years compared with >12 years (OR 1.82, 1.10 to 3.03, p = 0.020) and in patients living in Southern Europe compared with those living in Northern Europe (OR 2.25; 1.52 to 3.30, p<0.001). Overall resistance rate to metronidazole was 25% (A: 23%, B: 35%) and higher in children born outside Europe (A: adjusted. OR 2.42, 95% CI: 1.61 to 3.66, p<0.001). Resistance to both antibiotics occurred in 6.9% (A: 5.3%, B: 15.3%). Resistance to amoxicillin was exceptional (0.6%). Children with peptic ulcer disease (80/1180, 6.8%) were older than patients without ulcer (p = 0.001). Conclusion: The primary resistance rate of H pylori strains obtained from unselected children in Europe is high. The use of antibiotics for other indications seems to be the major risk factor for development of primary resistance.

Detection of Helicobacter pylori infection in children with a standardized and simplified 13C-urea breath test.

BACKGROUND The 13C-urea breath test, a reliable noninvasive method of detection of Helicobacter pylori in adults, needs validation in children. METHODS In order to evaluate the diagnostic accuracy of 13C-urea breath test in children, the results of this test performed in 144 children were correlated with the histology and culture of contemporaneous gastric (antral and fundic) biopsy specimens. The test was performed with 2 mg/kg body weight 13C-Urea (maximum, 100 mg) ingested after a fat-rich test meal. Samples of expired breath taken at 0, 5, 10, 20, and 30 minutes were assayed with mass spectrometry. Results were considered positive when the curve of excretion of labeled carbon dioxide in the expired breath increased by 5%O or more above the baseline. RESULTS Discrepancies in H. pylori status were observed in 14 children. To improve and simplify the test, the results were reanalyzed using different cutoff values for each sampling time. The best results, with sensitivity of 95.7% and specificity of 95.2%, were obtained with a cutoff of 3.5%O at 20 minutes. CONCLUSIONS The 13C-urea breath test is a reliable method for the noninvasive detection of H. pylori infection in children. The test can be simplified and its accuracy improved using only the 0- and 20-minute breath samples and a cutoff of 3.5%O instead of the classical 5%O used in adults. The need for modification of the cutoff value may reflect the higher production of endogenous CO2 in children.

Results from the pediatric European register for treatment of Helicobacter pylori (PERTH).

Background and Aim:  Data on the eradication treatment for childhood Helicobacter pylori are scanty. A register was established on the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) website to collect data on treatment performed by European pediatricians to ascertain what is practiced in the field.

Helicobacter pylori Modulation of Gastric and Duodenal Mucosal T Cell Cytokine Secretions in Children Compared with Adults

Background. In contrast to adults, ulcers are un‐common in Helicobacter pylori‐infected children. Since immunological determinants influence the outcome of H. pylori infection, we have investigated mucosal T cell responses in H. pylori‐infected children and compared them with those of adults and negative controls.

Multicenter Survey of Routine Determinations of Resistance of Helicobacter pylori to Antimicrobials over the Last 20 Years (1990 to 2009) in Belgium

ABSTRACT We analyzed the rates of antimicrobial resistance of Helicobacter pylori strains isolated from patients from 1990 to 2009 and identified risk factors associated with resistance. Gastric biopsy specimens were collected from several digestive disease centers in Brussels, Belgium. We routinely performed antimicrobial susceptibility testing for clarithromycin (CLR), metronidazole, amoxicillin, tetracycline, and ciprofloxacin. Evaluable susceptibility testing was obtained for 9,430 strains isolated from patients who were not previously treated for Helicobacter pylori infection (1,527 isolates from children and 7,903 from adults) and 1,371 strains from patients who were previously treated (162 isolates from children and 1,209 from adults). No resistance to amoxicillin was observed, and tetracycline resistance was very rare (<0.01%). Primary metronidazole resistance remained stable over the years, with significantly lower rates for isolates from children (23.4%) than for isolates from adults (30.6%). Ciprofloxacin resistance remained rare in children, while it increased significantly over the last years in adults. Primary clarithromycin resistance increased significantly, reaching peaks in 2000 for children (16.9%) and in 2003 for adults (23.7%). A subsequent decrease of resistance rates down to 10% in both groups corresponded to a parallel decrease in macrolide consumption during the same period. Multivariate logistic regression revealed that female gender, age of the patient of 40 to 64 years, ethnic background, the number of previously unsuccessful eradication attempts, and the different time periods studied were independent risk factors of resistance to clarithromycin, metronidazole, and ciprofloxacin. Our study highlights the need to update local epidemiological data. Thus, the empirical CLR-based triple therapy proposed by the Maastricht III consensus report remains currently applicable to our population.

Chronic hepatitis B infection: long term comparison of children receiving interferon alpha and untreated controls.

Objectives: To investigate the virological outcome of chronic hepatitis B (CH-B) in children who received interferon alpha (IFN) compared with no treatment. Methods: Seventy-four children with CH-B (median age, 6.1 years; 44 boys) selected from a cohort of 158 cases were included and divided into two groups: IFN-treated (n = 37) and control (n = 37). The controls were matched with the treated children by baseline alanine aminotransferase (ALT) levels, sex and age. The Kaplan-Meier method was performed to estimate the time to clearance of hepatitis B e antigen (HbeAg) and hepatitis B surface antigen (HbsAg). Results: Mean duration of follow-up was comparable in two groups (5.2 ± 3.8 years in treatment group versus 5.2 ± 3.7 years in control group, NS). HBeAg and HBsAg loss occurred in 20 (54.1%) and three treated children versus 13 (35.1%) and one untreated children (NS), respectively. The 7-year cumulative HBeAg and HBsAg clearance rates were 47.5% and 8.9% after the first visit in the treatment group versus 33.5% and 4.0% in untreated children (NS), respectively. Elevated baseline ALT (two times upper limit of normal) had a significant effect on the long-term cumulative rate of HBeAg seroconversion in treated patients (P = 0.01) but not in the untreated group. Conclusions: These findings show that the overall long-term virological outcome does not differ significantly between IFN-treated and untreated children but that a significant benefit of treatment on the long term rate of HBeAg seroconversion is obtained in children with higher baseline ALT levels.

Accuracy of serology and 13C-urea breath test for detection of Helicobacter pylori in children.

BACKGROUND Indirect noninvasive methods, such as the 13C-urea breath test and serology, can be useful for the detection of Helicobacter pylori infection in children. We analyzed retrospectively the diagnostic accuracy of these two methods. PATIENTS AND METHODS Between September, 1989, and October, 1996, H. pylori status was determined in 139 children by means of culture and histologic study of gastric biopsies. We performed 146 13C-urea breath tests and serologic assays (Cobas core; Roche). RESULTS H. pylori infection was detected in 91 of 139 (65%) children. The 13C-urea breath test was discordant with H. pylori status in 4 of 146 tests; serology was discordant in 24 and indeterminate in 7 of 146. The 13C-urea breath test was more sensitive than serology (98% vs. 79%, P < 0.01) but comparable in specificity (96% vs. 92%). The serology yielded false negative results more often in children younger than 5 years of age (P < 0.05). CONCLUSIONS The 13C-urea breath test is more reliable than serology for the detection of active H. pylori infection in children. Below 10 years of age serology is insufficiently sensitive for clinical purposes, whereas the 13C-urea breath test remains a reliable test.

Twelve year observation of primary and secondary antibiotic-resistant Helicobacter pylori strains in children

BACKGROUND The effectiveness of Helicobacter pylori eradication regimens is influenced by antibiotic susceptibility of infecting strains. Data concerning antibiotic resistance in children are limited. We report the evolution of primary and secondary resistance in a series of Belgian children during the last 12 years. PATIENTS AND METHODS From 1989 through 2000, H. pylori gastritis was diagnosed in 569 children, and antibiotic susceptibility tests were performed in 555. Eradication, using different schemes, failed in 128 of 457 treated children. After eradication failure antibiotic susceptibility determination was performed in 87 of 128. Comparison of antibiotic susceptibility of strains isolated from the gastric body and from the antrum was performed in 238 samples. RESULTS Resistance to amoxicillin was not observed. The rate of primary resistance to nitroimidazole derivatives was 18.0% (101 of 555) and remained constant throughout this period, whereas primary resistance to macrolides increased from an average of 6.0% (range, 0 to 10%) before 1995 to 16.6% (range, 10 to 25%, P < 0.001) thereafter. Antibiotic consumption in Belgium, especially macrolides, did not show important fluctuations during the study period. Secondary resistance developed in 39 of 87 patients (46%). Strains isolated from different gastric locations show identical susceptibility testing in all but 5 of 238. CONCLUSIONS Resistance of H. pylori to macrolides increased in our pediatric population which did not appear to correlate with macrolides prescription habits in our country. After eradication failure acquired secondary resistance was observed in one-half of the patients.

Sequential Therapy Versus Tailored Triple Therapies for Helicobacter pylori Infection in Children.

Aims: The aim of the study was to compare sequential versus tailored triple therapy regimens on Helicobacter pylori (H pylori) eradication rates in children and to assess the effect of antimicrobial susceptibility. Patients and Methods: Prospective, open-label, multicenter study. Children received randomly either a 10-day sequential treatment comprising omeprazole (OME) with amoxicillin for 5 days and OME, clarithromycin (CLA), and metronidazole (MET) for the remaining 5 days, or a 7-day triple therapy comprising OME with amoxicillin and CLA in cases of a CLA-susceptible strain or MET in cases of CLA-resistant strain. H pylori eradication was assessed by 13C-urea breath test. Results: One hundred sixty-five children, 95 girls and 70 boys, of median age 10.4 years, were included. The intention-to-treat (ITT) eradication rate was 76.9% (sequential 68/83 = 81.9%, triple therapy 59/82 = 71.9%, ns), and the per-protocol (PP) eradication rate was 84.6% (sequential 68/77 = 88.3%, triple therapy 59/73 = 81.8%, ns). Eradication rates tended to be higher using the sequential treatment, but the difference was only statistically significant for ITT analysis in children harboring both CLA- and MET-susceptible strains (87.8% vs 68.5%, odds ratio [OR] 3.3, P = 0.03). Both ITT and PP eradication rates were significantly lower with sequential treatment in CLA-resistant compared with CLA-susceptible strains (ITT: 56.2% vs 72.7%, OR 5.5, P = 0.008; PP 64.3% vs 80.0%, OR 7.9, P = 0.009). Both treatments were well tolerated. Conclusions: Sequential treatment is greatly effective for eradicating H pylori in children except in CLA-resistant strains. Sequential treatment can be used as a first-line therapy, but only in areas with a low CLA resistance rate.

Frequency and risk factors of gastric and duodenal ulcers or erosions in children: a prospective 1-month European multicenter study

There are no solid figures of the frequency of ulcer disease during childhood in Europe. We assessed its frequency and analyzed known risk factors. Patients and methods Ulcers, erosions, indications, and risk factors were recorded in all children undergoing an upper gastrointestinal endoscopy in a prospective study carried out during 1-month simultaneously in 19 centers among 14 European countries. Results Ulcers and/or erosions were observed in 56 out of 694 children. Children with ulcers/erosions were significantly older than those without lesions (10.3±5.5 vs. 8.1±5.7 years, P=0.002). Helicobacter pylori infection was present in 15 of 56 children (27%) where NSAIDs were used in eight, steroids in five, immune-suppressive drugs in five, antibiotics in six, antacids in one, H2-blockers in six and proton pump inhibitors in eight children (more than one risk factor was detected in 32 of 56 children). No risk factors were observed in 24 of 56 children (43%). The main indications for endoscopy were epigastric or abdominal pain (24%) and suspicion of gastroesophageal reflux disease (15%). Similarly, epigastric tenderness, hematemesis, melena, and weight stagnation were significantly associated with ulcers/erosions, whereas sex, H. pylori infection, socioeconomic and lifestyle factors were equally distributed. Conclusion Although limited by the short-time duration and the heterogeneity of the patients included throughout the 19 centers, our study shows a frequency of 8.1% of ulcers and/or erosions in children, occurring mainly in the second decade of life. H. pylori infection and gastrotoxic medications were less frequently implicated than expected.