13C-urea breath test for the diagnosis of Helicobacter pylori infection in children: a systematic review and meta-analysis

Background: The ¹³C‐urea breath test (¹³C‐UBT) is a safe, noninvasive and reliable method for diagnosing H. pylori infection in adults. However, the test has shown variable accuracy in the pediatric population, especially in young children. We aimed to carry out a systematic review and meta‐analysis to evaluate the performance of the ¹³C‐UBT diagnostic test for H. pylori infection in children. Methods: We conducted a systematic review of the PubMed, Embase and Liliacs databases including studies from January 1998 to May 2009. Selection criteria included studies with at least 30 children and reporting the comparison of ¹³C‐UBT against a gold standard for H. pylori diagnosis. Thirty‐one articles and 135 studies were included for analysis. Children were stratified in subgroups of <6 and ≥6 years of age, and we considered variables such as type of meal, cutoff value, tracer dose, and delta time for the analysis. Discussion: The ¹³C‐UBT performance meta‐analyses showed 1, good accuracy in all ages combined (sensitivity 95.9%, specificity 95.7%, LR+ 17.4, LR? 0.06, diagnostic odds ratio (DOR) 424.9), 2, high accuracy in children >6 years (sensitivity 96.6%, specificity 97.7%, LR+ 42.6, LR? 0.04, DOR 1042.7), 3, greater variability in accuracy estimates and on average a few percentage points lower, particularly specificity, in children ≤6 years (sensitivity 95%, specificity 93.5%, LR+ 11.7, LR? 0.12, DOR 224.8). Therefore, the meta‐analysis shows that the ¹³C‐UBT test is less accurate for the diagnosis of H. pylori infection in young children, but adjusting cutoff value, pretest meal, and urea dose, this accuracy can be improved.     

Role of 13C-urea breath test in experimental model of Helicobacter pylori infection in mice

Background: Animal models have been widely used to study Helicobacter pylori infection. Evaluation of H. pylori infection status following experimental inoculation of mice usually requires euthanasia. The ¹³C‐urea breath test (¹³C‐UBT) is both sensitive and specific for detection of H. pylori in humans. Thus, it would be very useful to have such a test with the same accuracy for the follow‐up of this infection in animal models of gastric infection. Accordingly, the purpose of this study was to develop and evaluate a ¹³C‐UBT method for following the course of H. pylori infection in a mouse model. Material and Methods: A total of 50 female C57BL/6 mice were gavaged three times with either 10⁸ colony‐forming units of H. pylori (n = 29) or saline solution only (n = 21). After 2 months of infection, mice were fasted for 14 hours and ¹³C‐UBT was performed using 300 μg of ¹³C‐urea. The mice were killed, and the stomach was removed and processed for immunohistochemistry and PCR. Results: The optimal time for breath sample collection in mice was found to be 15 minutes. The ¹³C‐UBT cutoff was set at 3.0‰δPDB. Using PCR as the gold standard, the sensitivity of ¹³C‐UBT and immunohistochemistry was 96.6 and 72.4%, respectively, while the specificity was 85.7 and 95.2%, respectively. Conclusions: ¹³C‐UBT was shown to be a reliable method for the detection of H. pylori infection in C57BL/6 mice and was even more accurate than immunohistochemistry. The use of ¹³C‐UBT in the mouse model of H. pylori infection can be very useful to detect the bacterium without the need to kill the animals in long‐term time course studies.     

13C-urea breath test during hospitalization for the diagnosis of Helicobacter pylori infection in peptic ulcer bleeding

Objective: To evaluate the accuracy of ¹³C‐urea breath test (UBT) to detect Helicobacter pylori infection in patients hospitalized with peptic ulcer bleeding and treated with proton pump inhibitors (PPIs). Methods: Patients hospitalized with peptic ulcer bleeding, and treated with omeprazole, had a first UBT performed the day after resuming oral feeding. Patients with a negative UBT during hospitalization underwent a repeated UBT 15 days after stopping PPIs. Results: The first UBT during hospitalization was positive in 86% of 131 patients. Time between admission and performance of the test was longer in patients with negative versus positive UBT (5.2 ± 0.7 versus 4.3 ± 0.5 days; p < .001). The repeated UBT became positive in 15 of 18 (83%) patients with a negative first UBT. In the multivariate analysis, the only variable associated with a negative first UBT was the time elapsed between admission and performance of the test (odds ratio = 6.6; 95%CI = 2.9–15.1). Conclusion: Most H. pylori‐positive patients with ulcer bleeding have a positive UBT (performed just after resuming oral feeding) despite previous treatment with high‐dose PPIs. Nevertheless, to preclude false‐negative results due to PPI therapy, the UBT should be performed as early as possible. If the infection cannot be demonstrated with this first UBT, H. pylori still needs to be definitively excluded with a second UBT performed after stopping PPIs.     

Treatment of Helicobacter pylori infection using a novel antiadhesion compound (3'sialyllactose sodium salt). A double blind,placebo-controlled clinical study

Background and Aim. 3′ sialyllactose sodium salt (3′SL) is an oligosaccharide that occurs naturally in human and bovine milk. It can inhibit the adhesion of H. pylori to human epithelial cells in vitro. The aim of this study was to test whether this oligosaccharide can suppress or cure H. pylori colonization in vivo and to determine its safety in humans. Methods. Seventy‐one consecutive dyspeptic patients with H. pylori infection documented by histology and ¹³C‐Urea Breath Test (UBT) were initially recruited to this study. Patients with UBT values < 15 were excluded, thus reducing the enrolment to 65 patients. They were given two different dosages of 3′SL (10 g or 20 g/day) in three daily administrations before meals or placebo for 4 weeks, according to a randomised double‐blind protocol. A standardized ¹³C‐UBT (using 100 mg of ¹³C labelled urea) was repeated in all patients at fixed intervals during treatment (at the end of weeks 1, 2 and 4) and 4 weeks after treatment withdrawal. Patients compliance and side‐effects were evaluated at each weekly visit. Results. Five patients were excluded from the PP analysis due to violation of the protocol (noncompliance, lost to follow‐up), whereas 61 patients completed correctly the study: 17 received 3′SL 10 g/day, 22 were treated with 3′SL 20 g/day and 21 were given placebo. The three treatment groups did not significantly differ in demographic or clinical patient characteristics. No serious adverse events were observed during therapy in any of the three groups. No patients became UBT negative (< 4) during or after treatment but UBT values decreased significantly during the study period in both treatment groups and placebo. Conclusions. Antiadhesive therapy was safe and well tolerated but did not suppress or cure H. pylori colonization in humans. The observed decrease in UBT values could be explained by a regression towards the mean effect.     

Helicobacter pylori eradication in patients on long-term H2 receptor antagonists. Economic and symptomatic benefits. A large prospective study in primary care

Background. A large proportion of patients in primary care are still being maintained on long‐term acid suppression, without any attempts to identify Helicobacter pylori status and to treat those that test positive. Objectives. To assess the prevalence and economic and symptomatic benefits of H. pylori eradication in patients maintained on long‐term H₂ receptor antagonists (H₂RA) in primary care. Patients and Methods. Patients on long‐term (i.e. 6 months or longer) H₂RA were identified from the computerised records of six practices in north England. Helicobacter pylori status was identified using serology and H. pylori positive patients were then offered standard 7‐day proton pump based triple therapy, followed by a urea breath test (UBT) to confirm H. pylori eradication. Those who had a positive UBT were offered a second line course of H. pylori eradication therapy. Follow up period was 1 year. The main outcome measures were improvement in dyspepsia symptom scores, amount of H₂RA being consumed, and economic benefits after H. pylori eradication. Results. One thousand and seven patients (1.5%) were identified on long‐term H₂RA, of whom 471 (46%) ultimately had their H. pylori serology assessed. Sixty‐three (297) percent of the patients tested had a positive serology for H. pylori, the majority of whom (58%, 172) had prior evidence of peptic ulcer disease. The mean duration of therapy and mean time since endoscopy/barium studies was significantly longer in patients with peptic ulcer disease compared to their counterparts with nonulcer dyspepsia and gastro‐oesophageal reflux disease, p= .0002 and .0001, respectively. After successful H. pylori eradication (which was possible in 84% of the patients), at the end of the 1‐year study period, on an intention to treat basis 62% of the patients could either stop or significantly reduce dosage of their H₂RA. There was also significant reduction in the mean dose of H₂RA being consumed and severity of symptoms at the end of the study period (p < .00001). Conclusion. Almost two‐thirds of patients on long‐term H₂RA in primary care will have a positive serology for H. pylori; the majority of these will have peptic ulcer disease. In over 60% of cases H. pylori eradication led to significant improvement in symptom scores and reduction in dosage of H₂RA being consumed. Cessation or reduction in long‐term H₂RA prescribing is cost effective.     

High eradication rates of Helicobacter pylori infection following sequential therapy: the Israeli experience treating naïve patients

Background: Helicobacter pylori eradication rates following triple therapy are decreasing. Cure rates as low as 57%, mainly to claritromycin resistance, have been reported in Israel. Studies performed in Italy have shown eradication rates of 93%, following sequential therapy. Our aim was to evaluate the effect of sequential therapy on eradication rates of H. pylori in naïve Israeli patients. Material and Methods: Consecutive patients referred for esophagogastroduodenoscopy with a positive rapid urease test and positive ¹³C urea breath test were included. Patients received omeprazole 20 mg bid and amoxicillin 1 g bid for 5 days followed by omeprazole 20 mg bid, clarithromycin 500 mg bid and tinidazole 500 mg bid for the subsequent 5 days. A second ¹³C urea breath test was performed at least 4 weeks after completion of therapy. Patients were asked to avoid antibiotics, bismuth compounds or proton pump inhibitor until after the second ¹³C urea breath test. Adverse effects were documented by a questionnaire. Results: One hundred and twenty‐four patients (mean age 56.1 ± 12.5 years, 55.6% women) were included; 120/124 (96.8%) completed treatment and performed the second ¹³C urea breath test. Two patients (1.6%) were lost to follow‐up; 2 (1.6%) were noncompliant with study regulations. One hundred and fifteen patients achieved eradication of H. pylori. The eradication rate was 95.8% by per protocol analysis and 92.7% by intention to treat analysis. Conclusion: The sequential regimen attained significantly higher eradication rates in naïve patients than usually reported for conventional triple therapy. Sequential therapy may be an alternative first‐line therapy in eradicating H. pylori in Israel.     

Quadruple therapy with medications containing either rufloxacin or furazolidone as a rescue regimen in the treatment of Helicobacter pylori-infected dyspepsia patients: a randomized pilot study

Background: The eradication rates of first‐line treatment for Helicobacter pylori infection are not satisfactory. Various regimens including quadruple therapies have been recommended as rescue therapies after the first H. pylori eradication attempt failed. Aims: To compare the efficacy and safety between quadruple therapies with medications containing either rufloxacin or levofloxacin in the Chinese nonulcer dyspepsia patients infected with H. pylori. Methods: One hundred and thirty‐eight patients after an unsuccessful 10‐day standard triple therapy were enrolled in this study. They were randomized to receive a 14‐day quadruple therapy with pantoprazole, bismuth citrate, and furazolidone in combination with either rufloxacin (Group Ruf, n = 70) or levofloxacin (Group Lev, n = 68). The H. pylori eradication was evaluated by ¹³C‐urea breath test 4 and 12 weeks after therapy was completed. Results: One hundred and twenty‐seven patients (65 in Group Ruf and 62 in Group Lev) completed the study. The H. pylori eradication rates in Group Ruf were 81.4% for intention‐to‐treat (ITT) analysis and 87.7% for per‐protocol (PP) analysis. The rates were statistically significantly higher than those in Group Lev (66.2% and 72.6%) (p < 0.05). There were no severe adverse effects found in these two groups. Conclusions: Fourteen‐day quadruple therapy with a combination of proton‐pump inhibitor, bismuth citrate, furazolidone, and rufloxacin is considered an effective and safe rescue therapy for H. pylori eradication after failure of standard triple treatment.     

Helicobacter pylori infection in asymptomatic children: comparison of diagnostic tests

Background. Childhood is known to be a major risk period for acquiring Helicobacter pylori infection. Studies of the epidemiology of H. pylori infection depend on the validity of the diagnostic tools used to detect the infection in the pediatric setting. This study aims to conduct a combination of diagnostic tests on the same children, evaluate the sensitivity and the specificity of IgG antibody testing compared with the ¹³C‐urea breath test, and examine the variability in the prevalence of H. pylori infection in asymptomatic children based on the use of different diagnostic tests. Methods. ¹³C‐urea breath test (¹³C‐UBT), whole blood FlexSure (systemic antibodies), and OraSure (salivary antibodies) tests were conducted on 287 asymptomatic children (151 boys, 136 girls; ages 2–18 years). The three tests were conducted on each child during the same day. The prevalence was calculated using each test independently. Results. H. pylori infection was detected in 32%, 22%, or 18% of the studied children, based on UBT, OraSure, or FlexSure, respectively. A total of 103 children tested positive for any one test (92 on UBT, 8 on FlexSure, 3 on OraSure), giving a prevalence of 35% based on the “parallel” method. Only 39 children tested positive in all three tests, giving a prevalence of 14% based on the “serial” method. Using the UBT as the gold standard, the sensitivity of FlexSure and OraSure were 48% and 65%, respectively, and the specificity of both tests was greater than 95%. When we applied the parallel method, the sensitivity and specificity of the combined antibody tests (FlexSure+OraSure) compared to the UBT were 71% and 95%, respectively. Conclusions. Among asymptomatic children, there is a wide variation in the prevalence of H. pylori infection based on the diagnostic test used. The study shows that antibody assays are less suitable than the UBT. However, under certain conditions, the IgG assays (combined systemic, salivary, or both) are less expensive alternative tools to the UBT for epidemiological studies in children.     

Does the Diagnostic Accuracy of the 13C‐Urea Breath Test Vary with Age Even After the Application of Urea Hydrolysis Rate?

Background: Endogenous CO₂ production may be a possible explanation for higher false‐positive results reported for ¹³C‐urea breath test (UBT) in children below 6 years. In this study, we evaluated whether age affects the diagnostic accuracy of the ¹³C‐UBT even after the application of urea hydrolysis rate (UHR) in children. Methods: A total of 612 ¹³C‐UBTs and endoscopic biopsies were performed on children divided into two groups; children under 6 years (n = 126) and children aged 6–18 years (n = 486). For ¹³C‐UBT, 75 mg ¹³C‐urea was ingested, and breath sample was collected 30 minutes later. Delta over baseline (DOB) was determined, and UHR was calculated to normalize the DOB values for endogenous CO₂ production. Results: There was significant difference between the DOB values of children under 6 years and those of children over 6 years in H. pylori‐positive (p = .029) and ‐negative groups (p = .002). On applying the UHR, no significant difference was observed between the UHR values of children under 6 years and those of children over 6 years in H. pylori‐positive (p = .877) and ‐negative groups (p = .427). In 12.6% children under 6 years, false‐positive results were observed on applying the DOB, and in 9.0% on applying the UHR (p = .125). Conclusions: The ¹³C‐UBT is a noninvasive method exhibiting high diagnostic accuracy with both UHR as well as DOB. However, high false‐positive results for ¹³C‐UBT were noted in children below 6 years on applying both UHR as well as DOB. Thus, this may not only be due to the effects of endogenous CO₂ production but also due to other factors.     

Evaluation of a four-drug, three-antibiotic, nonbismuth-containing "concomitant" therapy as first-line Helicobacter pylori eradication regimen in Greece

Background: The eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing worldwide as in Greece. Studies with new antibiotic combinations are needed to find better methods of eradication. Therefore, the aim of this study was to evaluate efficacy and tolerability of a 10‐day, four‐drug, three‐antibiotic, nonbismuth–containing concomitant regimen. Materials and Methods: This is a prospective, open‐label, multicenter study that included 131 patients infected with H. pylori. All patients were diagnosed with peptic ulcer disease or nonulcer dyspepsia by endoscopy. H. pylori infection was established by at least two positive tests among rapid urease test, gastric histology, and ¹³C‐urea breath test. For 10 days, all patients received esomeprazole 40 mg, amoxycillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg, all b.d. eradication was assessed with ¹³C urea breath test 8 weeks after the start of treatment. Intention‐to‐treat and per‐protocol eradication rates were determined. Results: One hundred and twenty‐seven of the 131 patients completed the study. At intention‐to‐treat analysis, the eradication rate was 91.6% (95% confidence interval (CI), 85.5–95.7%). For the per‐protocol analysis, the eradication rate was 94.5% (95% CI, 89–97.8%). Adverse events were noted in 42 of 131 (32.1%); drug compliance was excellent with 96.9% of the patients taking more than 90% of the prescribed medication. Conclusion: A 10‐day concomitant regimen appears to be an effective, safe, and well‐tolerated treatment option for first‐line H. pylori eradication in Greece.     

Efficacy and safety of faropenem in eradication therapy of Helicobacter pylori

Aims: While triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin is the standard therapy for Helicobacter pylori eradication, it is ineffective against clarithromycin‐resistant strains. To seek a better regimen for eradication therapy, we assessed the sensitivity of clinical strains seen in Japan to faropenem and then evaluated the efficacy and safety of eradication therapy containing this antibiotic. Methods: Minimum inhibitory concentrations (MICs) of faropenem were determined in 78 Japanese clinical H. pylori isolates using the agar dilution method. H. pylori‐positive patients were consecutively assigned to a 7‐day eradication therapy protocol with LAF (lansoprazole 60 mg/day, amoxicillin 2000 mg/day, and faropenem 600 mg/day), and then to a 14‐day protocol. The outcomes of the therapies were assessed by ¹³C‐urea breath tests. Results: All 78 strains showed MICs of faropenem that were equal to or less than 0.2 µg/mL. The eradication rates according to intention‐to‐treat analyses were 46.5% with the 7‐day therapy (n = 43) and 62.5% with the 14‐day therapy (n = 32). No special measures were required to treat the adverse events observed in approximately one‐third of the patients. Conclusions: Faropenem was found to have good antimicrobial action against H. pylori in vitro. The 14‐day LAF therapy successfully eradicated H. pylori in about two‐thirds of the patients although the incidence of adverse events was high.     

Acid inhibitory potency of twice a day omeprazole is not affected by eradication of Helicobacter pylori in healthy volunteers

Background & Aims. The acid inhibitory effect of proton pump inhibitors is reported to be greater in the presence than in the absence of an H. pylori infection. This study was undertaken to test the hypothesis that the acid inhibitory effect of omeprazole given twice a day is greater in H. pylori infected healthy volunteers than in the same individuals following eradication because of differences in the pharmacodynamics of omeprazole, greater duodenogastric reflux, the effects of ammonia produced by the H. pylori, or lower gastric juice concentrations of selected cytokines, which may inhibit gastric acid secretion. Materials and Methods. We undertook 24‐hour pH‐metry in 12 H. pylori‐positive healthy volunteers: (1) when on no omeprazole; (2) when on omeprazole 20 mg bid for 8 days; (3) 2 months after eradication of H. pylori and when on no omeprazole; and (4) after eradication of H. pylori and when on omeprazole 20 mg twice a day. Results. In subjects given omeprazole, eradication of H. pylori reduced pH and percentage pH ≥ 3, as well as increasing the area under the H⁺ concentration‐time curve. These differences were not due to alterations in (1) gastric juice concentrations of IL‐1α, IL‐8, IL‐13, epidermal growth factor, or bile acids; (2) serum gastrin concentrations; or (3) the pharmacokinetics of omeprazole. There was no change in the difference in the H⁺ concentration‐time curve ‘without omeprazole’ minus ‘with omeprazole’, when comparing ‘after’ versus ‘before’ eradication of H. pylori. Conclusions. Eradication of H. pylori was not associated with an alteration in the acid inhibitory potency when comparing the difference in gastric acidity ‘with’ versus ‘without’ omeprazole. When the results were expressed by simply taking into account the acid measurements while on omeprazole before versus after eradication of H. pylori, the acid inhibition with omeprazole was greater in the presence than in the absence of a H. pylori infection. The clinical significance of the small difference is not clear.     

Evaluation of a Western blot test,Helico blot 2.1, in the diagnosis of Helicobacter pylori infection in a pediatric population

Background. Noninvasive diagnostic tests are useful as screening tools for Helicobacter pylori infection in pediatric populations. The aim of this study was to evaluate performance of the immunoblot assay, Helico Blot 2.1, for the diagnosis of H. pylori infection in symptomatic children. Materials and Methods. Immunoblot assay was used for detection of IgG antibodies to specific H. pylori proteins and to a recombinant H. pylori antigen, CIM marker. The study was performed on sera collected from 134 symptomatic, untreated children (mean age, 9.1 ± 3.2 years; range, 1–14 years). H. pylori infection status was determined by culture, histology and rapid urease test. Results. Immunoblot assay yielded a positive result in 71 of the 72 infected patients (sensitivity 98.6%) and in eight of the 62 noninfected ones (specificity 87.1%). The predictive values for a positive and a negative result were 89.9% and 98.2%, respectively. The performance of the CIM band alone, as a marker for H. pylori infection status, was also evaluated. This band was present on the blot of 71 infected patients and on four of the 62 H. pylori‐negative patients. The sensitivity, specificity, PPV and NPV of the CIM antigen were 98.6%, 93.5%, 94.7% and 98.3%, respectively. Conclusions. The immunoblot assay Helico Blot 2.1 is a suitable noninvasive test for the serodiagnosis of H. pylori infection in children. The good level of performance demonstrated by the novel recombinant antigen CIM suggests it may be a useful contribution to the qualitative and quantitative performance of the Helico Blot 2.1 in pediatric populations.     

Eradication of Helicobacter pylori infection improves blood pressure values in patients affected by hypertension

Background. Arterial hypertension is a risk factor for atherosclerosis of whose pathogenesis is unknown. Growing evidence underscores the causative role of endothelial dysfunction. A possible association between Helicobacter pylori infection and cardiovascular and autoimmune disorders has been found. The release of cytotoxic substances either of bacterial origin or produced by the host may represent mediators of these systemic sequelae. The aim of our study was to determine the prevalence of H. pylori infection in hypertensive patients and the effects of H. pylori eradication on blood pressure and on digestive symptoms. Materials and Methods. Seventy‐two hypertensive patients (34 male and 38 female; mean age 53 ± 12 years) and 70 normotensive controls (35 male and 35 female; mean age 52 ± 10 years) were enrolled. All patients were subjected to a first ambulatory blood pressure monitoring (ABPM) at enrollment, a ¹³C urea breath test and a test for IgG‐CagA antibodies, and completed the validated dyspepsia questionnaire. H. pylori‐positive patients were treated with triple therapy (amoxicillin, clarithromycin and ranitidine bismute citrate) for 7 days. Control of eradication was assessed by ¹³C urea breath test, and all patients underwent a second ABPM 6 months after enrollment. Results. H. pylori infection was 55% in hypertensive patients, with 90% CagA positivity, and 50% in controls, with 60% CagA positivity. At the first ABPM, blood pressure values were similar in H. pylori‐positive and ‐negative individuals; positive patients showed a significant increase in pyrosis and epigastric pain compared to negative patients. H. pylori was eradicated in 80% of patients and in 85% of controls. At the second ABPM, we found a statistically significant decrease in 24‐hour mean blood pressure values when compared to the first ABPM only in the eradicated hypertensive group. Conclusions. Our study demonstrated a significant decrease in blood pressure values, in particular in diastolic blood pressure values, after H. pylori eradication in hypertensive patients. A high prevalence of CagA positivity was found. The association between cardiovascular disease and H. pylori infection seems pronounced only in CagA‐positive patients. The possible links between hypertensive disease and H. pylori infection may involve the activation of the cytokine cascade with the release of vasoactive substances from the primary site of infection, or molecular mimicry between the CagA antigens of H. pylori and some peptides expressed by endothelial cells and smooth muscle cells.     

First-time urea breath tests performed at home by 36,629 patients: a study of Helicobacter pylori prevalence in primary care

Background: The aim of the current study was (1) to describe the use of a ¹³C‐urea breath test (UBT) that was performed by patients at their homes as a part of a test‐and‐treat strategy in primary care and (2) to investigate the prevalence of Helicobacter pylori in patients taking a first‐time UBT. Material and Methods: The patients performed UBTs at home based on the discretion of the general practitioner and mailed the breath bags to a central laboratory for analysis. Each patient was identified by a unique civil registration number. The study was population‐based, and the background population was approximately 700,000 people. Results: From 2003 to 2009, 44,487 UBTs were performed. Of these, 36,629 were first‐time UBTs. In total, 726 of 45,213 breath bags received (1.6%) were unable to be analyzed because of errors with the bags. For both women and men who were ≤45 years of age, positive H. pylori declined over the time course of the study (women: 19.6% in 2003 to 17.6% in 2009, p < .01; men: 20.7% in 2003 to 16.9% in 2009, p < .001). Patients who were older than 45 years had significantly higher positive H. pylori results than younger patients. Conclusions: A test‐and‐treat system was possible to implement that allowed patients to perform UBTs at their homes. The results of the first‐time UBTs demonstrated that approximately one of five patients who presented with dyspepsia in the clinical setting of Danish primary care was infected with H. pylori.     

Effectiveness and safety of repeated quadruple therapy in Helicobacter pylori infection after failure of second-line quadruple therapy: repeated quadruple therapy as a third-line therapy

Backgrounds: Quadruple therapy using a proton‐pump inhibitor, bismuth, metronidazole, and tetracycline is a standard second‐line therapy for Helicobacter pylori infection, achieving an eradication rate of about 80% in Korea. A standard third‐line therapy is not currently established, although various protocols have been proposed. We performed this study to evaluate the effectiveness of a retrial with quadruple therapy before starting a third‐line treatment with new drugs. Materials and Methods: In 80 of 746 patients treated with a second‐line quadruple therapy at the Korea University Ansan Hospital between January 2002 and September 2010, treatment for H. pylori had failed, and 45 of these patients were eligible for this study. Eradication of H. pylori was assessed by repeated endoscopy or by the ¹³C‐urea breath test at least 4 weeks after therapy. The patients with treatment failure were treated again with quadruple regimen for 2 weeks and reevaluated for treatment effectiveness and safety. Results: The eradication rate with second‐line quadruple therapy was 86.9%. Of the 80 patients who failed treatment for H. pylori with the initial second‐line quadruple therapy, 64 patients were treated again with the same regimen. Of the 45 retreated patients in this study, three patients were lost to follow‐up and two complied poorly with medication. The eradication rate in the 40 patients retreated was 75.0% at per‐protocol analysis. Seventeen patients experienced mild adverse events. Conclusions: A retrial of quadruple therapy before use of a third‐line therapy may be safe and effective for patients who fail to respond to second‐line quadruple therapy.     

Quantitative PCR of string-test collected gastric material: A feasible approach to detect Helicobacter pylori and its resistance against clarithromycin and levofloxacin for susceptibility-guided therapy

Background

As the reduced eradication rate of Helicobacter pylori (H. pylori), we introduced string-test and quantitative PCR (qPCR) for susceptibility-guided therapy innovatively. The practicality of the string test was evaluated.

Methods

It was an open-label, non-randomized, parallel, single-center study, in which subjects tested by ¹³C- urea breath test (UBT) and string-qPCR were enrolled. Based on the results of string-qPCR, we calculated clarithromycin and levofloxacin resistance rates and gave ¹³C-UBT positive patients 14 days susceptibility-guided bismuth quadruple therapy. In the empirical therapy group, we retrospectively analyzed the treatment results of ¹³C-UBT positive patients also treated with bismuth quadruple at Shenzhen Luohu People's Hospital from January 2021 to May 2022. The eradication rate was compared between susceptibility-guided therapy and empirical therapy groups.

Results

The diagnosis of H. pylori infection using the string-qPCR had an overall concordance rate of 95.9% with the ¹³C-UBT results. Based on the results of string-qPCR, the clarithromycin and levofloxacin resistance rates were 26.1% and 31.8%, respectively. The patients who were given 14 days susceptibility-guided bismuth-based quadruple therapy achieved a high H. pylori eradication rate of 91.8%. Retrospective analysis of patient treatment data from January 2021 to May 2022 available in the hospital database revealed an overall success rate of 82.3% for those who received empirical bismuth-based quadruple therapies, which is marginally significantly lower than that of the string-qPCR susceptibility-guided group (p = 0.084).

Conclusion

The high treatment success rate of 91.8% indicates that the string-qPCR test is a valuable and feasible approach for clinical practice to help improve H. pylori treatment success rate.     

Nonbismuth quadruple (concomitant) therapy: empirical and tailored efficacy versus standard triple therapy for clarithromycin-susceptible Helicobacter pylori and versus sequential therapy for clarithromycin-resistant strains

Background:  Using quadruple clarithromycin‐containing regimens for Helicobacter pylori eradication is controversial with high rates of macrolide resistance. Aim:  To evaluate antibiotic resistance rates and the efficacy of empirical and tailored nonbismuth quadruple (concomitant) therapy in a setting with cure rates <80% for triple and sequential therapies. Methods:  209 consecutive naive H. pylori‐positive patients without susceptibility testing were empirically treated with 10‐day concomitant therapy (proton pump inhibitors (PPI), amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg; all drugs b.i.d.). Simultaneously, 89 patients with positive H. pylori culture were randomized to receive triple versus concomitant therapy for clarithromycin‐susceptible H. pylori, and sequential versus concomitant therapy for clarithromycin‐resistant strains. Eradication was confirmed with ¹³C‐urea breath test or histology 8 weeks after completion of treatment. Results:  Per‐protocol (PP) and intention‐to‐treat eradication rates after empirical concomitant therapy without susceptibility testing were 89% (95%CI:84–93%) and 87% (83–92%). Antibiotic resistance rates were: clarithromycin, 20%; metronidazole, 34%; and both clarithromycin and metronidazole, 10%. Regarding clarithromycin‐susceptible H. pylori, concomitant therapy was significantly better than triple therapy by per protocol [92% (82–100%) vs 74% (58–91%), p = 0.05] and by intention to treat [92% (82–100%) vs 70% (57–90%), p = 0.02]. As for antibiotic‐resistant strains, eradication rates for concomitant and sequential therapies were 100% (5/5) vs 75% (3/4), for clarithromycin‐resistant/metronidazole‐susceptible strains and 75% (3/4) vs 60% (3/5) for dual‐resistant strains. Conclusions:  Empirical 10‐day concomitant therapy achieves good eradication rates, close to 90%, in settings with multiresistant H. pylori strains. Tailored concomitant therapy is significantly superior to triple therapy for clarithromycin‐susceptible H. pylori and at least as effective as sequential therapy for resistant strains.     

A modified bismuth-containing quadruple therapy including a short course of furazolidone for Helicobacter pylori eradication after sequential therapy failure

Background: Helicobacter pylori eradication has still remained a challenge, especially in case of failure to novel treatments. Therefore, we designed a study to evaluate the effects of a modified bismuth‐containing quadruple therapy including a short course of furazolidone on a group of patients whose sequential therapy had been unsuccessful. Materials and Methods: Thirty‐six H. pylori‐positive patients who had previously failed a clarithromycin‐containing sequential therapy enrolled the study. They received pantoprazole (40 mg‐bid), amoxicillin (1 g‐bid), and bismuth subcitrate (240 mg‐bid) for 2 weeks and furazolidone (200 mg‐bid) just during the first week. Eight weeks after treatment, H. pylori eradication was reassessed using C14‐urea breath test. Results: Thirty five patients completed the study. H. pylori eradication rates were 80.6% (95% CI = 67.6–93.5) and 82.9% (95% CI = 70.6–95.2) according to intention‐to‐treat and per‐protocol analyses, respectively. All patients had excellent compliance to treatment, and no one interrupted therapy owing to adverse effects. Conclusion: Regarding the eradication rate (>80%), low price, and very low adverse effects, a 2‐week bismuth‐containing quadruple regimen including a short course of furazolidone can be an encouraging regimen for second‐line H. pylori eradication in case of sequential therapy failure. Possibly, it can be improved by alterations in dose, dosing intervals, and/or duration.     

Low efficacy of clarithromycin including sequential regimens for Helicobacter pylori infection

Background: Sequential treatment for Helicobacter pylori (H. pylori) appears to achieve a better eradication rate than triple therapy. However, most of the data have been reported from the Italy, and studies from different population are needed before it is recommended in clinical practice. The present study aimed to assess and compare the efficacy of two separate clarithromycin including sequential regimens in Turkey which is well known with high clarithromycin and metronidazole resistance to H. pylori. Methods: Consecutive H. pylori ‐positive patients with non‐ulcer dyspepsia were randomly allocated to one of the two sequential regimens; the first group was given lansoprazole 30 mg b.i.d. plus amoxicillin 1 g b.i.d. for the first week, followed by lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg t.i.d. for the second week (LA‐CM). The second arm was given the same regimen but tetracycline500 g q.i.d. instead of metronidazole (LA‐CT). H. pylori was detected with urea breath test (UBT) and histology before enrollment. UBT was repeated at 6th weeks after treatment. Results: A total of 200 patients were enrolled in groups and 179 of them completed their protocols. The cumulative per protocol (“PP”) and intention‐to‐treat (“ITT”) eradication rates were 74.3% and 66.5% in all patients, respectively. Both “PP” (78.2% vs 70.1%) and “ITT” (72% vs 61%) eradication rates were better in LA‐CT group than LA‐CM group, but the differences were not statistically significant (p > .05). Both regimens were well tolerated, and the incidence of adverse effects was comparable. Conclusion: Two weeks clarithromycin including sequential regimens with metronidazole or tetracycline were not achieved acceptable eradication rates in Turkey.