Review article: diagnosis of Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection can be diagnosed by invasive techniques requiring endoscopy and biopsy (histological examination, culture, polymerase chain reaction) and by noninvasive techniques (serology, urea breath test, urine or blood, detection of H. pylori antigen in stool specimen). At present, no single test can be absolutely relied upon to detect colonization by H. pylori, and a combination of two tests is recommended if feasible. The tests used should depend on the clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy, and the availability of the tests. Some clinical circumstances warrant invasive studies, principally patients with alarm symptoms (bleeding, weight loss, etc.) as well as older patients with new-onset dyspepsia. Endoscopy may also be advisable in patients who have failed eradication therapy and need culture and antimicrobial sensitivity testing to determine an appropriate regimen. Recent studies have also demonstrated that a strategy to 'test and treat' for H. pylori in uninvestigated, young (< 50 years), dyspeptic patients in primary care is safe and reduces the need for endoscopy. Indeed, a number of clinical guidelines recommend noninvasive testing followed by treatment of H. pylori for dyspeptic patients in primary care based on clinical and economic analyses.     

Review article: the treatment of Helicobacter pylori infection

The discovery of Helicobacter pylori has stimulated great interest in its role in gastritis, non-ulcer dyspepsia and peptic ulceration. Treatment regimens to eradicate this organism from gastric mucosa have also received considerable attention. Current recommendations limit the use of triple drug combinations only to specific patient groups.     

Review article: the treatment of refractory Helicobacter pylori infection

The occurrence of refractory Helicobacter pylori infection is increasing. When the bacteria are not eradicated it means that the antibiotics have not reached the gastric mucosa at a sufficient concentration and over a sufficient time lapse to kill them. The main reasons for this are poor patient compliance, resistant bacteria, low gastric pH and a high bacterial load. Therefore, when administering a new treatment, it is important to choose antibiotics which do not face resistance problems and which increase the dosage of antisecretory drugs and the duration of treatment and, if possible, to add a topical agent such as bismuth salt. The recommended empirical strategy is to prescribe quadruple therapy or, alternatively, 2-week triple therapy including amoxicillin-metronidazole, tetracycline-metronidazole or amoxicillin-rifabutin. However, when H. pylori is susceptible, clarithromycin can still be used. In the case of a high level of metronidazole resistance, furazolidone can be employed. In each case, it is important to ensure good patient compliance, and counselling is helpful in this regard. However, the best approach remains the prevention of refractory H. pylori infection and, for this purpose, antimicrobial susceptibility testing before first-line therapy is important and should be encouraged.     

Review article: the cost of diagnosing Helicobacter pylori infection

Non-invasive testing and treatment for Helicobacter pylori has been recommended for dyspeptic patients in primary care and a number of recent studies have demonstrated the cost-effectiveness of this approach. As the prevalence of H. pylori infection declines, the positive and negative predictive values of individual tests will change. Cost-effectiveness is important in determining the appropriate test in individual populations. Recent studies have shown that the stool antigen test and the urea breath test have high sensitivity and specificity in the detection of H. pylori infection before and after therapy. Cost-effectiveness studies have shown that when the prevalence of H. pylori infection is low or intermediate, serological tests have relatively poor accuracy compared with the stool test or the urea breath test. In populations with low or intermediate prevalence (<60%) these tests should be preferred to ELISA serology or office-based whole-blood test or serology. This is particularly true when the prevalence of H. pylori infection is less than 30% as is seen in many developed countries. When the prevalence of H. pylori infection is high (>60%), low-cost antibody tests are cost-effective.     

Review article: Helicobacter pylori infection in peptic ulcer haemorrhage

In this overview, medical advice for routine clinical practice regarding peptic ulcer haemorrhage (PUH) is given, based on the extensive literature about Helicobacter pylori and the controversial results about the interaction of H. pylori infection and nonsteriodal anti-inflammatory drug (NSAID) use. PUH remains an important emergency situation with an incidence between 32 and 51/100 000 persons per year. There is a high association between H. pylori infection and peptic ulcer disease. The association between H. pylori infection and PUH is less clear, but a strong argument for the aetiological role is the fact that eradication of H. pylori decreases recurrence of bleeding. NSAID use is another important risk factor for PUH. H. pylori infection and NSAID use seem to act independently, although some studies show a synergistic interaction while other studies report that H. pylori is protective against the development of PUH in NSAID users. All patients with PUH should be tested for H. pylori infection, regardless of the use of NSAIDs. Because invasive tests are less sensitive in PUH patients, negative tests in patients with no other risk factors should be confirmed by serology or urea breath test (UBT). Eradication therapy with a proton pump inhibitor or ranitidine bismuth citrate-based triple therapy should be given to all H. pylori-positive patients. Only for nonaspirin-NSAID users does the effect of eradication therapy on the healing of gastric ulcers remain controversial, but currently we also advise eradication of H. pylori in this subgroup. After eradication therapy, acid-suppressant therapy is advised to heal the ulcer. The success of eradication should always be confirmed because of the risk of recurrence of peptic ulcer disease and bleeding in H. pylori-infected patients.     

Review article: Helicobacter pylori infection from pathogenesis to treatment--a critical reappraisal

The main areas of this review are Helicobacter pylori and disease pathogenesis; the relationship of H. pylori to lower gastrointestinal diseases, liver disease and extra-gastrointestinal conditions; the relationship of H. pylori to gastro-oesophageal reflux disease; infection in the very young and very old; diagnostic techniques; and management of H. pylori infections with particular emphasis on eradication regimens and antibiotic resistance.     

Review article: gastro-oesophageal reflux disease and Helicobacter pylori infection

Gastro-oesophageal reflux disease (GERD) and Helicobacter pylori infection are common conditions that frequently coexist. Controversy continues regarding the role of H. pylori infection in GERD. The results of some studies suggest that eradication of H. pylori may increase the risk for developing GERD, and some experts have suggested that chronic H. pylori infection may be of benefit. This article reviews the data on H. pylori infection and GERD and its treatment.     

Review article: rifabutin in the treatment of refractory Helicobacter pylori infection

Aliment Pharmacol Ther 2012; 35: 209–221

Summary

Background Even with the current most effective treatment regimens, a relevant proportion of patients will fail to eradicate Helicobacter pylori infection. Aim To evaluate the role of rifabutin in the treatment of H. pylori infection. Methods Bibliographical searches were performed in MEDLINE. Data on the efficacy of rifabutin‐containing regimens on H. pylori eradication were combined and meta‐analysed using the generic inverse variance method. Results Rifabutin shows good in vitro activity against H. pylori. Mean H. pylori rifabutin resistance rate (calculated from 11 studies including 2982 patients) was 1.3% (95% confidence interval = 0.9–1.7%). When only studies including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.6%). On the other hand, higher values of rifabutin resistance were calculated (1.59%) when only post‐treatment patients were considered. Overall, mean H. pylori eradication rate (intention‐to‐treat analysis) with rifabutin‐containing regimens (1008 patients) was 73% (67–79%). Respective cure rates for second‐line (223 patients), third‐line (342 patients) and fourth/fifth‐line (95 patients) rifabutin therapies were 79% (67–92%), 66% (55–77%) and 70% (60–79%) respectively. For treating H. pylori infection, almost all studies have administered rifabutin 300 mg/day; this dose seems to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10‐ to 12‐day regimens are generally recommended. The mean rate of adverse effects was 22% (19–25%). Myelotoxicity is the most significant, although this complication was rare. Until now, all patients have recovered of leucopenia uneventfully in a few days, and there have been no reports of infection or other adverse outcomes related to it. Conclusion Rifabutin‐containing rescue therapy constitutes an encouraging strategy after multiple (usually three) previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin.     

Review article:invasive and non-invasive tests for Helicobacter pylori infection

There are two general ways in which a diagnosis of infection by Helicobacter pylori can be made: by using either an invasive or non-invasive procedure. The invasive procedures involve an endoscopy and biopsy. A biopsy is essential because often the mucosa may appear macroscopically normal but nevertheless be inflamed. A biopsy is obtained by histological examination, culture, polymerase chain reaction or detection of the presence of urease activity in biopsy material. The non-invasive tests that can be used to diagnose the infection are serology, detection of labelled metabolic products of urea hydrolysis in the breath (13CO2, 14CO2), the urine or the blood, and detection of H, pylori antigen in a stool specimen. At present no single test can be relied upon to detect definitely colonization by H. pylori, and a combination of two is recommended if this is feasible. The choice of the test to be used is not straightforward and may vary according to the clinical condition and local expertise.     

Review article: natural history and epidemiology of Helicobacter pylori infection

Helicobacter pylori is a common bacterium infecting about half the world's population. It is causally linked with a diverse spectrum of gastrointestinal clinical disorders including peptic ulcer disease, gastric cancer, and gastric MALT lymphoma. The principal reservoir is the human stomach, and transmission probably occurs by person-to-person passage. Prevalence rates are generally much higher in developing countries compared to developed countries, although there are subgroups within many regions with higher H. pylori prevalence than in the general population. The prevalence of H. pylori varies by geographical location, ethnic background, socioeconomic conditions, and age. Recent studies suggest decreasing prevalence in developed countries or those with rapidly improving socioeconomic conditions. Comparative studies of the two fully sequenced H. pylori genomes are providing understanding of its large genetic diversity and bacterial virulence factors. The discovery of the type IV secretion system in H. pylori and its role in translocation of the CagA protein from the bacterial cell into the host epithelial cell provides insight into how host-bacterial interaction may lead to host disease. Cytokine promoter polymorphisms are determinants important in host gastric acid secretion status. Understanding the changing trends in H. pylori epidemiology, details of its transmission pathways, and the bacterial and host determinants leading to gastroduodenal disease remain the challenges in this area. Global epidemiological studies, advances in technology, and medical interventions have converged to help clarify the mechanisms of interaction between this ubiquitous micro-organism and its host that result in its diverse clinical manifestations.     

Review article: nitroimidazole resistance in Helicobacter pylori

The efficacy of a nitroimidazole-containing regimen for the treatment of Helicobacter pylori infection is decreased by nitroimidazole resistance. Nitroimidazoles are meta- bolized by H. pylori by several nitro-reductases of which an oxygen-insensitive NADPH nitroreductase encoded by the rdxA gene is the most important. Null mutations in this gene are associated with resistance.
Susceptibility testing to nitroimidazoles may give variable results. This is not only related to the slow growth under specific conditions, but also to variability in the activity of the other nitroreductases and the ability to deactivate toxic metabolites of an NI and to repair DNA damage. Moreover, co-infections with resistant and susceptible bacteria are frequently found. The presence of nitroimidazole resistance is related to the previous use of this drug. The prevalence of resistance is rising and nowadays 10–50% of the isolates are resistant.
Resistance reduces the efficacy of a treatment regimen to a variable degree. This is related to efficacy of the other components of the regimen and the treatment duration. Whether a nitroimidazole is still effective in resistant strains remains unresolved.
When nitroimidazole resistance is present, a nitro-imidazole-containing regimen should be avoided or a regimen with other highly effective components should be used.     

Review article: treatment of Helicobacter pylori infection and factors influencing eradication

Currently available Helicobacter pylori eradication therapies are considered very effective and safe. The most recent eradication guidelines proposed in the Maastricht 2-2000 Consensus Report recommend the use of proton pump inhibitors (standard b.d.) along with clarithromycin (500 mg b.d.) and amoxycillin (1000 mg b.d.) or metronidazole (500 mg b.d.) for a minimum of 7 days. The combination of amoxycillin and clarithromycin is preferred because it may favour best results with a second-line proton pump inhibitor quadruple therapy. The recommended second-line therapy includes a combination of a proton pump inhibitor (standard b.d.) with bismuth salt (subsalicylate/subcitrate 120 mg q.d.s.), metronidazole (500 mg t.d.s.), and tetracycline (500 mg q.d.s.) for a minimum of 7 days. Extended proton pump inhibitor-based triple therapy can be used if bismuth is not available. Specialists should manage subsequent failures. Based on direct and indirect evidence from well-designed studies and clinical experience, eradication is recommended in gastric and duodenal ulcers, MALToma, atrophic gastritis, postgastric cancer resection, and in first-degree relatives of gastric cancer patients. The most common reason for treatment failure is poor compliance with eradication guidelines. Antibiotic resistance may be a significant factor in certain geographical areas. Proton pump inhibitors are an integral part of the eradication regimens as proved by meta-analyses of clinical trials. Novel agents used in secondary failure are few and depend on the use of new antibiotics. The role of H. pylori-specific antibiotics, probiotics, and vaccines is not established as yet. Widespread acceptance of the eradication guidelines should be regarded as the single most important factor in eradication success.     

Review article: gastric cancer and Helicobacter pylori

Gastric cancer is the second commonest cause of death from malignancy in the world. Its pathogenesis is comparatively well understood and its aetiology multifactorial. Non-cardia gastric cancer usually arises in a stomach that has been inflamed over a long period and where atrophy and intestinal metaplasia have supervened. The commonest cause of gastric inflammation is infection with Helicobacter pylori. Colonization with this organism increases the relative risk of developing this cancer by about six [Helicobacter and Cancer Collaborative Group. Gut 2001; 49: 347-53]. Its likelihood increases with the severity and extent of the gastritis. Severity is influenced by the virulence of the infecting organism, the genetics of the host, bile reflux, dietary factors and the presence of hypochlorhydria which influences the extent, as well as the severity, of the inflammation. The only predisposing factor which can easily be manipulated is H. pylori infection, which can be successfully treated in 80-90% of cases using a 1-week therapeutic regimen.     

Review article: Helicobacter pylori and gastric adenocarcinoma

Gastric adenocarcinoma is still the second most common cause of death from cancer, even though it is on the decline in developed countries. Although H. pylori gastritis appears to be a necessary antecedent to the development of gastric adenocarcinoma, it is not a sufficient factor in and of itself. Other required factors for the progression of this disease are poorly understood. Patients with antral predominant gastritis seem protected from the disease, while patients with pangastritis are predisposed to both diffuse- and intestinal-type adenocarcinoma. Development of a vaccine against H. pylori might yield promising results in decreasing the incidence of gastric adenocarcinoma.     

Review article: Helicobacter pylori and reflux disease

The falling prevalence of Helicobacter pylori infection and related diseases (peptic ulcer disease, gastric cancer) in developed countries has been paralleled by an increased recognition of gastro-oesophageal reflux and its complications. These epidemiological data do not support a role for H. pylori in the pathogenesis of reflux disease, but suggest a negative association with the increasing incidence of oesophageal diseases. This has led some investigators to propose a 'protective' role of H. pylori infection against the development of oesophageal diseases. In these patients, pre-existing lower oesophageal sphincter dysfunction, susceptibility to reflux, unmasking of latent reflux and the patterns and severity of gastritis are probably important factors contributing to the development of oesophageal diseases. The most likely mechanism by which H. pylori infection may protect against reflux is by decreasing the potency of the gastric refluxate in patients with corpus-predominant gastritis. The prevalence of H. pylori infection in patients with reflux disease is probably no greater than that in those without reflux, and there are conflicting data indicating that reflux symptoms or erosive oesophagitis develop after H. pylori eradication. It is also unclear whether H. pylori augments the antisecretory effects of proton pump inhibitors or accelerates the development of atrophic gastritis.     

Review article: Helicobacter pylori vaccines-the current status

In this review, we take a look at the current status in the development of a vaccine against the human pathogenic bacterium, Helicobacter pylori, a major aetiological factor in peptic ulcer disease and gastric adenocarcinoma. Various animal models are now in use from mice infected with H. pylori, through gnotobiotic pigs and primates to ferrets naturally infected with their own Helicobacter, H. mustelae. A significant problem remains the requirement for a suitable mucosal adjuvant. Detoxification or the use of low doses of adjuvants already available may provide a solution and new immune stimulating compounds have been tested with some success. New approaches include the delivery of Helicobacter antigens by DNA immunization, microparticles or live vectors such as attenuated salmonella and the examination of alternative routes of vaccine administration. The phenomenon of post-immunization gastritis and improvements in vaccine efficacy are also discussed. A major area of interest is the mechanism by which immunization actually influences Helicobacter colonization. This remains a mystery: antibodies appear to be unimportant whereas CD4+ T-cells essential. Finally, a viewpoint is given on whom should be immunized when a final vaccine becomes available.     

Review article: Helicobacter pylori and uninvestigated dyspepsia

Although dyspepsia is a very common disorder, the incidence of Helicobacter pylori infection in Western medical clinics is very low (20-35%). In cases where H. pylori is detected, elimination of it may be cost-effective in the long term, but even eradication is not a guarantee for long-term relief. Further studies to determine the connection between H. pylori and dyspepsia need to be completed before H. pylori eradication becomes the treatment of choice for that minority of patients. The majority of dyspeptic patients are not as simple to diagnose, and may need several empirical trials of therapy, or more specific diagnostic assessment.     

Review article: Helicobacter pylori and NSAID gastropathy

Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori are known to share a number of pathogenic mechanisms, but there is no evidence to show a significant synergic action between the two risk factors. Studies assessing this subject have differed in almost every aspect of their methodology, including the definition of a NSAID user as well as the types, doses, duration and their indications for NSAID use. They also differed in their end-points, the definition of dyspepsia and the regimes used for eradication of H. pylori. However, some conclusions may be drawn from the results of clinical trials. In H. pylori-positive patients without mucosal lesions, NSAIDs may aggravate dyspeptic symptoms but, with the exception of elderly patients, they do not present a definite major risk of gastric and duodenal lesions and, above all, of ulcer-correlated complications. So what recommendations can be made with regard to H. pylori eradication in patients requiring treatment with NSAIDs? The microorganism and the anti-inflammatory drugs are undoubtely independent causes of gastric and duodenal damage. Patients taking NSAIDs who are found to have gastric or duodenal ulcers should therefore be tested for the bacterium and specifically treated, since H. pylori and NSAID-induced ulcers may be macroscopically indistinguishable. Whether asymptomatic patients taking NSAIDs should be tested and treated for H. pylori infection is still a matter of debate.     

Review article: Helicobacter pylori and nonulcer dyspepsia

Although up to 50% of patients diagnosed with nonulcer dyspepsia (NUD) have Helicobacter pylori infection and underlying chronic gastritis, it remains controversial whether any causal relationship exists. The results of worldwide epidemiological studies have been unconvincing. No clear-cut link has been documented between H. pylori and any specific symptom profile or pathophysiological mechanism in NUD. In the randomized controlled trials, methodological weaknesses may explain in part the conflicting results, but even in the well-conducted trials controversy persists. Although meta-analyses have attempted to resolve the issue, inherent methodological difficulties with meta-analysis remain a problem. Moreover, even the methodologically sound meta-analyses have reported conflicting results. In addition, predictors of treatment response remain obscure, and there continue to be theoretical concerns about the treatment of H. pylori infection in all patients with NUD. Hence, the management of these patients is challenging, but eradication of H. pylori infection may be beneficial in a small subgroup of cases with NUD that cannot be identified before treatment.     

Review article: esomeprazole in the treatment of Helicobacter pylori

Proton pump inhibitor-based triple therapy is the most commonly used treatment for eradication of Helicobacter pylori, with pooled eradication rates of approximately 90%. In the USA, per protocol eradication rates with 10-day proton pump inhibitor-based triple therapy are approximately 85%. Esomeprazole, a new proton pump inhibitor that is the S-isomer of omeprazole and produces a greater inhibition of acid secretion than omeprazole, has recently been evaluated in the treatment of H. pylori. Seven-day twice daily triple therapy with esomeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg provided intention-to-treat eradication rates of 86-90% and per protocol eradication rates of 90-91% in duodenal ulcer patients in Europe and Canada. Ten-day triple therapy with esomeprazole 40 mg q.d.s., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. achieved intention-to-treat eradication rates of 77-78% and per protocol eradication rates of 84-85% in USA duodenal ulcer patients. Thus, esomeprazole triple therapy with amoxicillin and clarithromycin is effective in the treatment of H. pylori, with eradication rates comparable to previously studied proton pump inhibitor-based triple therapies.