Author(s): Thung, I; Aramin, H; Vavinskaya, V; Gupta, S; Park, JY; Crowe, SE; Valasek, MA | Abstract: BackgroundHelicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma.AimTo review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms.MethodsA PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing.ResultsThe prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced.ConclusionsSince the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance.

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Review article: the global emergence of Helicobacter pylori antibiotic resistance.

Antibacterial photodynamic therapy (APDT) has drawn increasing attention from the scientific society for its potential to effectively kill multidrug-resistant pathogenic bacteria and for its low tendency to induce drug resistance that bacteria can rapidly develop against traditional antibiotic therapy. The review summarizes the mechanism of action of APDT, the photosensitizers, the barriers to PS localization, the targets, the in vitro-, in vivo-, and clinical evidence, the current developments in terms of treating Gram-positive and Gram-negative bacteria, the limitations, as well as future perspectives. Relevance for patients: A structured overview of all important aspects of APDT is provided in the context of resistant bacterial species. The information presented is relevant and accessible for scientists as well as clinicians, whose joint effort is required to ensure that this technology benefits patients in the post-antibiotic era.

Antibacterial photodynamic therapy: overview of a promising approach to fight antibiotic-resistant bacterial infections.

Core tip: Because of the rising frequency of antimicrobial resistance, management of Helicobacter pylori (H. pylori) infections is a challenge for physicians. We found global frequency rate of resistance is high in Africa. The most sensitive drug is rifabutin and the lowest sensitive drug is metronidazole in the world. The worldwide H. pylori antibiotic resistance to clarithromycin and levofloxacin has increased during the last 6 years. Resistances to antimicrobial agent’s reports describe dramatic decrease of antibiotics efficacy.

Prevalence of antibiotic resistance in Helicobacter pylori: A recent literature review

Background Since "Helicobacter pylori (H. pylori) infection" was set as the indication in the Japanese Society for Helicobacter Research (JSHR) Guidelines 2009, eradication treatment for H. pylori gastritis is covered under insurance since 2013 in Japan, and the number of H. pylori eradication has rapidly increased. Under such circumstances, JSHR has made the third revision to the "Guidelines for diagnosis and treatment of H. pylori infection" for the first time in 7 years. Methods The Guideline Committee held 10 meetings. Articles published between the establishment of the 2009 Guidelines and March 2016 were reviewed and classified according to the evidence level; the statements were revised on the basis of this review. After inviting public comments, the revised statements were finalized using the Delphi method. Results There was no change in the basic policy that H. pylori infectious disease is an indication for eradication. Other diseases presumed to be associated with H. pylori infection were added as indications. Serum pepsinogen level, endoscopic examination, and X-ray examination were added to the diagnostic methods. The effects of 1-week triple therapy consisting of potassium-competitive acid blocker (P-CAB), amoxicillin, and clarithromycin have improved, and high eradication rates can also be expected with proton pump inhibitors (PPI) or P-CAB combined with amoxicillin and metronidazole. If the susceptibility test is not performed, the triple PPI or P-CAB/amoxicillin/metronidazole therapy should be chosen, because the PPI/amoxicillin/metronidazole combination demonstrated a significantly higher eradication rate than PPI/amoxicillin/clarithromycin. In the proposal for gastric cancer prevention, we divided gastric cancer prevention measures by age from adolescent to elderly, who are at an increased gastric cancer risk, and presented measures for gastric cancer prevention primarily based on H. pylori eradication. Conclusion We expect the revised guidelines to facilitate appropriate interventions for patients with H. pylori infection and accomplish its eradication and prevention of gastric cancer.

Guidelines for the management of Helicobacter pylori infection in Japan: 2016 Revised Edition.

Helicobacter pylori (H. pylori) is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. H. pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth–containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility–based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan–containing triple therapies, quintuple therapies, high–dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori.

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Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance

Background
Eradication of Helicobacter pylori (H. pylori) at a younger age is considered to be effective in preventing gastric cancer. This study assessed the characteristics of eradication therapy in young patients.

Materials and Methods
We enrolled 1073 patients with H. pylori infection between 2000 and 2013. The subjects were divided into three groups according to age into the young (≤30 years), middle-aged (31–50 years), and elder (≥51 years) groups. We also examined 472 cases to investigate clinical eradication characteristics.

Results
The rate of clarithromycin (CAM) resistance was 57.9%, 34.5%, and 35.2% in the young, middle-aged, and elder group, respectively, in 2012–2013 and was significantly higher in the young group than in the elder group (p = .01). Metronidazole (MNZ) resistance was similar among the three groups at each time point. While CAM resistance rose over the study period, MNZ resistance was noted to have decreased of late. The overall initial eradication success rate was 91.9% (95% CI, 89.1–94.1) in our cohort. Eradication efficiency was comparable in the young, middle-aged, and elder group at 94.3% (95% CI, 87.4–97.5), 90.2% (95% CI, 82.9–94.6), and 91.8% (95% CI, 88.1–94.5) respectively. Side effects such as skin rash were observed in 14.8%, 3.9%, and 3.5% of the respective groups. There were significant differences in the incidence of side effects between the young group and other groups (p < .05, respectively).

Conclusion
Since CAM resistance and the incidence of side effects are higher in young individuals, it is especially important to select eradication regimens based on testing for antimicrobial susceptibility.

Antimicrobial resistance and characteristics of eradication therapy of Helicobacter pylori in Japan: a multi-generational comparison.

https://www.omicsonline.org/2161-069X/2161-069X.C1.031_002.pdf

Screening to identify and eradicate Helicobacter pylori infection in teenagers in Japan

Superficially located enlarged lymphoid follicles characterise nodular gastritis

Background/aims This study examined the accuracy of endoscopic evaluation for determining the Helicobacter pylori infection status in patients with mild atrophy who might not exhibit characteristic endoscopic findings. Methods Forty endoscopists determined the H. pylori infection status of 50 randomly presented H. pylori-positive and H. pylorinegative cases on the basis of a list of established findings. Results The median clinical endoscopy experience was 7 years (range, 1-35 years), including 22 board-certified endoscopists (55%) of the Japan Gastroenterological Endoscopy Society. The mean accuracy rate of endoscopic diagnosis was 67% and was unrelated to experience status (experienced vs. trainee: 69% vs. 65%, p=0.089) and total years of experience (R2 =0.022). The most frequently selected endoscopic findings were regular arrangement of collecting venules (59%), atrophy (45%), and red streak (22%), which had fair accuracy rates of 67%, 65%, and 73%, respectively. By contrast, the accuracy rates of nodularity (89%) and mucosal swelling (77%) were highest. The 20 endoscopists who more frequently identified these findings diagnosed H. pylori infection significantly more accurately than did the other endoscopists (71% vs. 64%, p=0.008). Conclusions Careful attention to nodularity and mucosal swelling in patients with mild atrophy may enhance diagnosis, enable prompt treatment, and avoid possible long-term carcinogenesis.

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Accuracy of Endoscopic Diagnosis for Mild Atrophic Gastritis Infected with Helicobacter pylori.

A 46-year-old man underwent gastrointestinal endoscopy while visiting the hospital for a general physical check-up. Coarse mucosa in the antrum with superficial erosions was found by endoscopic gastrointestinal examination, but no atrophic changes were seen in the corpus. Histopathological examination of gastric biopsy specimens revealed mucosa-associated lymphoid tissue (MALT) lymphoma. Although Helicobacter pylori was not detected in our patient, H. heilmannii was identified histologically and by polymerase chain reaction analysis, resulting in the diagnosis of H. heilmannii-associated gastric MALT lymphoma. We successfully eradicated H. heilmannii and achieved complete remission of gastric MALT lymphoma by antibiotic therapy. H. heilmannii usually causes milder gastritis than H. pylori, but it has been more closely associated with MALT lymphoma. As such, when H. pylori infection is excluded in patients with gastric MALT lymphoma, physicians should next consider the possibility of H. heilmannii. Furthermore, our research suggests that eradication therapy is effective for treatment of localized H. heilmannii-associated gastric MALT lymphoma.

A case of Helicobacter heilmannii -associated primary gastric mucosa-associated lymphoid tissue lymphoma achieving complete remission after eradication

Takuma Okamura

Papers

Antimicrobial resistance and characteristics of eradication therapy of Helicobacter pylori in Japan: a multi-generational comparison.

Screening to identify and eradicate Helicobacter pylori infection in teenagers in Japan

Superficially located enlarged lymphoid follicles characterise nodular gastritis

Accuracy of Endoscopic Diagnosis for Mild Atrophic Gastritis Infected with Helicobacter pylori.

A case of Helicobacter heilmannii -associated primary gastric mucosa-associated lymphoid tissue lymphoma achieving complete remission after eradication