Linda Best

Is Helicobacter pylori eradication associated with gastroesophageal reflux disease

OBJECTIVES:A recent report has suggested an association between Helicobacter pylori eradication and the development of gastroesophageal reflux disease (GERD). We therefore assessed the incidence of GERD among comparable patients having undergone successful versus failed H. pylori eradication in a controlled trial. We also compared the H. pylori strains in the subjects that developed GERD to those that did not.METHODS:Patients with a history of proven duodenal ulcer and H. pylori infection were randomised into a H. pylori eradication study. Patients subsequently underwent gastroscopy with gastric biopsies every 3 months for 1 yr. At each visit, the presence of GERD symptoms and endoscopic esophagitis were noted, and the incidence of these variables among patients in whom H. pylori eradication was successful was compared to those in whom it was not. In a subgroup, the presence of the cagA, cagE, and vacA genotypes and of cagA antibodies were determined.RESULTS:Of 98 patients randomized into this study, 11 dropped out before determination of H. pylori eradication, leaving 87 patients with analyzable results. H. pylori eradication was successful in 63 (72%). By the end of the follow-up period, patients with GERD symptoms or endoscopic esophagitis were more prevalent in the successful than in the failed eradication group (37% [95% CI: 25–50%] vs 13% [95% CI: 3–32%], p = 0.04, 95% CI for the difference: 6–42%), as were patients with GERD symptoms alone (29% [95% CI: 18–41%] vs 8% [95% CI: 1–27%], p = 0.04, 95% CI for the difference: 4–36%) or esophagitis alone (21% [95% CI: 12–33%] vs 4% [95% CI: 0–21%], p = 0.10, 95% CI for the difference: 4–29%, respectively). Multivariate analysis revealed no significant association between the incidence of symptoms or esophagitis and age, gender, Quetelet index, caffeine or alcohol intake, smoking, weight change, or the presence of a hiatus hernia. There were also no differences in the prevalence of H. pylori genotypes from patients who developed GERD as compared to those who did not.CONCLUSIONS:In this patient population, the incidence of new GERD-type symptoms or endoscopic esophagitis was greater in patients in whom successful eradication was achieved. This difference does not appear to be attributable to weight gain, habits, or specific H. pylori strains.

Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases

OBJECTIVE:Helicobacter pylori (H. pylori) is a recognized pathogen, but it may also have a protective effect for gastroesophageal reflux disease (GERD). We compared the prevalence of potential virulence factors (cagA, cagE, vacA genotypes) in GERD to other upper gastrointestinal diseases and controls.METHODS:A total of 405 patients underwent gastroscopy with H. pylori isolation and serum testing. Patient diagnostic subgroups were prospectively defined. Genotypes were determined by amplification using polymerase chain reaction. CagA antibodies were determined by western blot, enzyme-linked immunosorbent, and flow microsphere immunofluorescent assays.RESULTS:Patients were grouped as follows: nonulcer dyspepsia (26%), GERD (20%), gastric ulcer (17%), duodenal ulcer (12%), gastric cancer (6%), or controls (19%). The cagA gene was present in 94–97% of subjects in all categories, but the cagA antibody was less prevalent in nonulcer dyspepsia (69%, 95% CI: 48–86%, p = 0.02) and GERD (69%, CI: 39–91%, p < 0.05) than in those with gastroduodenal pathology including gastric ulcer, duodenal ulcer, and gastric cancer (92%, CI: 81–98%). The cagE gene and vacA S1 genotype were more frequent in patients with gastroduodenal pathology (p < 0.01). GERD was associated with a significantly lower rate of vacA S1 genotype than controls (29% (CI: 10–56%) versus 80% (CI: 59–93%), p < 0.01). The vacA S1 genotype was associated with the presence of cagA antibodies.CONCLUSIONS:The cagE and vacA S1 genotypes are more prevalent in patients with peptic ulcer or gastric cancer, suggesting a potential function in virulence for these genes. However, the vacA S1 genotype was also more prevalent in controls than GERD, suggesting a potential protective effect against GERD.

Multilaboratory Comparison of Proficiencies in Susceptibility Testing of Helicobacter pylori and Correlation between Agar Dilution and E Test Methods

ABSTRACT Susceptibility testing was performed at seven Canadian microbiology laboratories and the Helicobacter Reference Laboratory, Halifax, Nova Scotia, Canada, to assess susceptibility testing proficiency and the reproducibility of the results for clarithromycin and metronidazole and to compare the Epsilometer test (E test) method to the agar dilution reference method. Control strain Helicobacter pylori ATCC 43504 (American Type Culture Collection) and 13 clinical isolates (plus duplicates of four of these strains including ATCC 43504) were tested blindly. The National Committee for Clinical Laboratory Standards (NCCLS) guidelines for agar dilution testing were followed, and the same suspension of organisms was used for agar dilution and E test. Antimicrobials and E test strips were provided to the investigators. Methods were provided on a website (www.Helicobactercanada.org ). Each center reported MICs within the stated range for strain ATCC 43504. Compared to the average MICs, interlaboratory agreements within 2 log2 dilutions were 90% (range, 69 to 100%) for clarithromycin by agar dilution, with seven very major errors [VMEs], and 85% (range, 65 to 100%) by E test, with three VMEs. Interlaboratory agreements within 2 log2 dilutions were 83% (range, 50 to 100%) for metronidazole by agar dilution, with six VMEs and eight major errors (MEs), and 75% (range, 50 to 94%) by E test, with four VMEs and four MEs. At lower and higher concentrations of antibiotic, E test MICs were slightly different from agar dilution MICs, but these differences did not result in errors. When a standardized protocol based on NCCLS guidelines was used, most participants in this study correctly identified clarithromycin- and metronidazole-susceptible and -resistant strains of H. pylori 93% of the time by either the agar dilution or E test method, and the numbers of errors were relatively equivalent by both methods.

Helicobacter pylori: Primary Susceptibility to Clarithromycin in vitro in Nova Scotia

Resistance to antimicrobial agents is a major determinant of the efficacy of regimens to eradicate Helicobacter pylori. Clarithromycin (CLA) has become one of the most commonly used antibiotics for treatment of H pylori infection. In this study, the rate of primary resistance to CLA in H pylori isolated from patients was determined. One hundred sixty-two strains were recovered from patients before treatment. Strains were grown and inoculated onto Mueller-Hinton agar with 7% sheep blood. CLA epsilometer gradient agar diffusion test (E test) strips were used to test for susceptibility. Appropriate control organisms were tested to validate the assay. Plates were incubated at 37 degrees C in a microaerophilic atmosphere for up to five days. E test results were easy to interpret. Strains were considered resistant if the minimum inhibitory concentration (MIC) was 2 micrograms/mL or greater. Three strains were resistant (two strains with MIC 8 micrograms/mL and one strain with MIC 12 micrograms/mL) and 159 strains were sensitive (MICs ranged from less than 0.016 to 0.38 micrograms/mL). Ninety per cent of the strains had MICs of 0.023 micrograms/mL. Primary resistance was 1.8%. These susceptibility data support the use of CLA for the treatment of H pylori in the Nova Scotia population.

Rescue Therapy Using a Rifabutin-Based Regimen is Effective for Cure of Helicobacter pylori Infection

OBJECTIVE To evaluate the efficacy of rescue therapy using rifabutin, amoxicillin and a proton pump inhibitor (PPI) in the eradication of Helicobacter pylori in patients who have failed at least one course of PPI-based triple therapy. METHODS The present study was a single-centre case series of 16 consecutive patients who had received at least one course of standard eradication therapy. Pretreatment evaluation included endoscopy with biopsies for histology and culture for H pylori infection. Treatment consisted of a one-week regimen containing a PPI twice daily, amoxicillin (A) 1 g twice daily and rifabutin (R) 300 mg once daily (PPI-AR). Post-treatment evaluation consisted of a repeat endoscopy with biopsy for histology and culture, or a validated urea breath test at least four weeks after treatment was completed. Pretreatment antibiotic susceptibility to metronidazole, clarithromycin and A was evaluated using a validated epsilometer test. RESULTS Of the 16 patients, four had previously received one course of triple therapy, 10 had received two courses and two had received more than two courses. The overall success rate of PPI-AR was 63% (10 of 16). Resistance to A was 0% (0 of 13), metronidazole 77% (10 of 13), clarithromycin 70% (seven of 10), and both metronidazole and clarithromycin 60% (six of 10). There was no correlation between resistance patterns and cure rate. CONCLUSIONS An R-containing regimen such as PPI-AR is a viable option as rescue therapy for H pylori infection.

Use of LARA-urea breath test in the diagnosis of Helicobacter pylori infection in children and adolescents: A preliminary study

BACKGROUND An accurate diagnosis of Helicobacter pylori infection in children currently relies upon histological assessment or culture of gastric biopsies obtained at endoscopy. Noninvasive testing would permit simpler assessment of children with dyspeptic symptoms. The primary aim of the present study was to prospectively evaluate a novel urea breath testing method in children undergoing diagnostic assessment of dyspeptic symptoms and secondarily to consider the roles of other noninvasive tests in these children. METHODS Laser associated ratio analysis (LARA)-13C urea breath testing was performed on children presenting with upper gastrointestinal symptoms for diagnostic endoscopy. Serum and stool were collected for performance of serology and stool antigen testing, respectively. Histology and culture of endoscopic biopsies of the gastric antrum were used to establish H pylori infection status. RESULTS Eight (36%) of 22 children were H pylori-positive by histology or culture of gastric biopsies. Urea breath testing showed a sensitivity of 75%, but specificity of 100%. The deletion of a test meal from the urea breath test protocol in eight patients did not alter the utility of the test. Serology provided sensitivity of 87.5%, but a specificity of only 75%. Stool antigen testing in eight available samples provided sensitivity of 50% and specificity of 100%. CONCLUSIONS The LARA-urea breath testing method provided less sensitivity in this group of children than suggested from previous studies. However, urea breath testing in children is easy to complete and provides rapid noninvasive results. Breath testing protocols require standardization; for instance, the addition of a test meal may not be necessary in older children. Although noninvasive tests for the presence of H pylori in children may provide accurate results and can be considered for use in the initial assessment of dyspeptic children, further work is required to establish the most accurate testing methods.

Chemical structure of bismuth compounds determines their gastric ulcer healing efficacy and anti-Helicobacter pylori activity.

The recognition of the role of Helicobacterpylori in the pathogenesis of peptic ulcer disease hasled to renewed interest in bismuth pharmacology sincebismuth compounds have both anti-Helicobacter pylori and ulcer healing properties. The precisechemical structure of current bismuth compounds is notknown. This has hindered the development of new andpotentially more efficacious formulations. We havecreated two new compounds,2-chloro1,3-dithia-2-bismolane (CDTB) and1,2-[bis(1,3-dithia-2-bismolane)thio]ethane (BTBT), withknown structure. In a rat model of gastric ulceration,BTBT was comparable to, and CDTB was significantly less effective thancolloidal bismuth subcitrate in healing cryoprobeinducedulcers. However, both BTBT and CDTB inhibited H. pylorigrowth in vitro at concentrations <1/10 that of colloidal bismuth subcitrate. The effects onulcer healing are not mediated by suppression of acidsecretion, pepsin inhibition, or prostaglandinproduction. Since all treated animals received the same amount of elemental bismuth, it appears thatthe efficacy of bismuth compounds varies with compoundstructure and is not simply dependent on the delivery ofbismuth ion. Because the structure of the novel compounds is known, our understanding of therelationship of bismuth compound structure and tobiologic activity will increase. In the future it may bepossible to design other novel bismuth compounds with more potent anti-H. pylori and ulcer healingeffects.