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대한소화기내시경학회> Gut and Liver> Efficacy of Tegoprazan for Improving the Susceptibility of Antimicrobial Agents against Antibiotic-Resistant Helicobacter pylori

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Efficacy of Tegoprazan for Improving the Susceptibility of Antimicrobial Agents against Antibiotic-Resistant Helicobacter pylori

Jung Won Lee , Nayoung Kim , Ryoung Hee Nam , Jeong Eun Yu , Joo Hee Son , Sun Min Lee , Dong Ho Lee
  • : 대한소화기내시경학회
  • : Gut and Liver 15권1호
  • : 연속간행물
  • : 2021년 01월
  • : 53-60(8pages)

DOI


목차

INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONFLICTS OF INTEREST
ACKNOWLEDGEMENTS
AUTHOR CONTRIBUTIONS
ORCID
REFERENCES

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Background/Aims: Favorable outcomes of potassium-competitive acid blocker (PCAB)-containing eradication therapy have been reported. In fact, tegoprazan, a recently developed PCAB, was presumed to show good eradication efficacy even for resistant Helicobacter pylori. We aimed to investigate the anti-H. pylori efficacy of tegoprazan compared with that of vonoprazan.
Methods: A total of 220 resistant clinical H. pylori isolates were utilized. The anti-H. pylori efficacy of PCABs was determined by evaluating the minimum inhibitory concentrations (MICs) of clarithromycin, fluoroquinolone, metronidazole, and amoxicillin in combination with vonoprazan or tegoprazan by the agar dilution method. The impact of the mutations responsible for resistance development, such as 23S rRNA, gyrA, rdxA, frxA, and pbp1 mutations, was also analyzed.
Results: H. pylori growth was significantly inhibited in a medium containing 1 μg/mL clarithromycin with tegoprazan (128 μg/mL). The MICs of clarithromycin (46.3%), fluoroquinolone (46.7%), metronidazole (55.6%), and amoxicillin (34.5%) against resistant H. pylori isolates improved after tegoprazan administration. Tegoprazan demonstrated more frequent susceptibility acquisition with metronidazole than with vonoprazan (20.6% vs 4.7%, p=0.014). However, there were no significant differences depending on the mutational status of each antimicrobial agent.
Conclusions: Tegoprazan administration may improve the susceptibility of antimicrobial-resistant H. pylori, independent of acid suppression. (Gut Liver 2021;15:53-60)

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간행물정보

  • : 의약학분야  > 내과학
  • : KCI등재
  • : SCI
  • : 격월
  • : 1976-2283
  • :
  • : 학술지
  • : 연속간행물
  • : 2007-2021
  • : 1333


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1Fecal Microbiota Transplantation Is Effective for the Treatment of Partially Treated Clostridioides difficile Infection

저자 : Young-seok Cho

발행기관 : 대한소화기내시경학회 간행물 : Gut and Liver 15권 1호 발행 연도 : 2021 페이지 : pp. 1-2 (2 pages)

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2Precision Medicine Approaches to Prevent Gastric Cancer

저자 : Juntaro Matsuzaki , Hitoshi Tsugawa , Hidekazu Suzuki

발행기관 : 대한소화기내시경학회 간행물 : Gut and Liver 15권 1호 발행 연도 : 2021 페이지 : pp. 3-12 (10 pages)

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Gastric cancer remains one of the most common causes of cancer-related death worldwide, although the incidence is declining gradually. The primary risk factor for gastric cancer is Helicobacter pylori infection. The Kyoto global consensus report recommends eradication of H. pylori in all infected patients. However, because it is difficult to stratify the risk of carcinogenesis among patients with a history of H. pylori infection, annual endoscopic surveillance is performed for everyone after eradication. This review summarizes the current approaches used to screen for novel molecules that could assist in the diagnosis of gastric cancer and reduce mortality. Most well-studied molecules are tissue protein biomarkers expressed by the gastric epithelium and associated with metaplasia-dysplasia-carcinoma sequences. Other strategies focus on the origin of cancer stem cell-related markers, such as CD44, and immune reaction-related markers, such as matrix metallopeptidases. Noninvasive methods such as blood-based approaches are more attractive. Serum pepsinogen levels predict the severity of gastric mucosal atrophy before H. pylori eradication, whereas plasma ghrelin levels are associated with atrophy even after eradication. Cell-free DNAs and RNAs are attractive tools for the early detection of cancer. These ideas could lead to the development of more personalized strategies for cancer prevention based on cuttingedge technologies. (Gut Liver 2021;15:3-12)

3Helicobacter pylori Treatment Strategies in Singapore

저자 : Tiing Leong Ang , Daphne Ang

발행기관 : 대한소화기내시경학회 간행물 : Gut and Liver 15권 1호 발행 연도 : 2021 페이지 : pp. 13-18 (6 pages)

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The management of Helicobacter pylori infection in Singapore remains a clinical challenge. Similar to other regions, there has been an increase in antibiotic resistance rates through the years. Nonetheless, over the past two decades, clarithromycin-based triple therapy has continued to be used as the first line treatment option, with an eradication rate exceeding 90%, although the accepted treatment duration must now be lengthened from 1 to 2 weeks to maintain efficacy. Concomitant and sequential therapies did not demonstrate superiority over standard triple therapy. Current empiric second line treatment utilizes either bismuth-based quadruple therapy or levofloxacin-based triple therapy, but outcomes remain less than ideal. Identifying options to further improve treatment success rates is challenging. Strategies being considered include the use of potent acid suppressants, such as vonoprazan, and H. pylori culture and antibiotic susceptibility testing-guided therapy. (Gut Liver 2021;15:13-18)

4Expanding Indications for Liver Transplant: Tumor and Patient Factors

저자 : Kevin Ka-wan Chu , Kelly Hiu-ching Wong , Kenneth Siu-ho Chok

발행기관 : 대한소화기내시경학회 간행물 : Gut and Liver 15권 1호 발행 연도 : 2021 페이지 : pp. 19-30 (12 pages)

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During the past few decades, liver transplant has developed from a high-mortality procedure to an almost routine procedure with good survival outcomes. The development of living donor liver transplant has increased the availability of liver grafts, and the scope of indications for liver transplant has been expanding ever since. The aim of this review is to provide an overview of such an expansion of scope. Various criteria have been proposed to expand the eligibility of patients with hepatocellular carcinoma exceeding the Milan criteria for liver transplant. Furthermore, liver transplant is increasingly performed as a treatment modality for cholangiocarcinoma, neuroendocrine liver metastasis and colorectal liver metastasis. The number of elderly patients receiving liver transplant is on the rise. Combined organ transplantation has also been adopted to treat patients with multiple organ failure. Going forward, further development of preoperative noninvasive predictors in tumor, patient and even donor factors is needed to identify patients at risk of poor outcomes and hence optimize patient management. (Gut Liver 2021;15:19-30)

5Molecular Features of the Serrated Pathway to Colorectal Cancer: Current Knowledge and Future Directions

저자 : Carla Satorres , María García-campos , Marco Bustamante-balén

발행기관 : 대한소화기내시경학회 간행물 : Gut and Liver 15권 1호 발행 연도 : 2021 페이지 : pp. 31-43 (13 pages)

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Serrated lesions are the precursor lesions of a new model of colorectal carcinogenesis. From a molecular standpoint, the serrated pathway is thought to be responsible for up to 30% of all colorectal cancer cases. The three major processes of this molecular mechanism are alterations in the mitogen-activated protein kinase pathway, production of the CpG island methylation phenotype, and generation of microsatellite instability. Other contributing processes are activation of WNT, alterations in the regulation of tumor suppressor genes, and alterations in microRNAs or in MUC5AC hypomethylation. Although alterations in the serrated pathway also contribute, their precise roles remain obscure because of the various methodologies and definitions used by different research groups. This knowledge gap affects clinical assessment of precursor lesions for their carcinogenic risk. The present review describes the current literature reporting the molecular mechanisms underlying each type of serrated lesion and each phenotype of serrated pathway colorectal cancer, identifying those areas that merit additional research. We also propose a unified serrated carcinogenesis pathway combining molecular alterations and types of serrated lesions, which ends in different serrated pathway colorectal cancer phenotypes depending on the route followed. Finally, we describe some key issues that need to be addressed in order to incorporate the newest technologies in serrated pathway research and to improve overall knowledge for developing specific prevention strategies and new therapeutic targets. (Gut Liver 2021;15:31-43)

6Clinicopathologic Features of Submucosal Papillary Gastric Cancer Differ from Those of Other Differentiated-Type Histologies

저자 : Seung Yong Shin , Jie-hyun Kim , Myeong-cherl Kook , Do Youn Park , Keun Won Ryu , Il Ju Choi , Sung Hoon Noh , Hyunki Kim , Yong Chan Lee

발행기관 : 대한소화기내시경학회 간행물 : Gut and Liver 15권 1호 발행 연도 : 2021 페이지 : pp. 44-52 (9 pages)

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Background/Aims: Papillary gastric cancer (GC) is classified as differentiated adenocarcinoma, together with well-differentiated (WD) and moderately differentiated (MD) adenocarcinoma. This study evaluated the risk of lymph node metastasis (LNM) in submucosal (SM) invasive papillary GC compared with other differentiated early GC types.
Methods: This retrospective study involved three tertiary hospitals and enrolled 1,798 lesions with differentiated SM invasive GC treated with curative gastrectomy between March 2001 and December 2012. All pathology slides were reviewed, and clinicopathologic findings associated with LNM, including tumor size, location, gross type, ulceration, depth and width of SM invasion, and lymphovascular invasion (LVI), were analyzed.
Results: The proportion of SM papillary GC was 2.8% (n=51). SM papillary GC was associated with larger tumor size and deeper and wider SM invasion than other differentiated GC types. LNM was significantly higher in the papillary type than in the MD and WD types. LNM was found in 27.5% of SM papillary GC patients (WD: 9.0%, MD: 21.2%). LVI was the only significant risk factor for LNM in SM papillary GC. The depth or width of SM invasion was not associated with LNM in papillary GC. Lower third location or elevated gross appearance was significantly associated with LVI.
Conclusions: SM papillary GC had the highest LNM rate, with features different from those of other differentiated SM invasive GCs. The treatment strategy for SM papillary GC should be carefully approached, especially for lesions located in the lower third or of the elevated gross type. (Gut Liver 2021;15:44-52)

7Efficacy of Tegoprazan for Improving the Susceptibility of Antimicrobial Agents against Antibiotic-Resistant Helicobacter pylori

저자 : Jung Won Lee , Nayoung Kim , Ryoung Hee Nam , Jeong Eun Yu , Joo Hee Son , Sun Min Lee , Dong Ho Lee

발행기관 : 대한소화기내시경학회 간행물 : Gut and Liver 15권 1호 발행 연도 : 2021 페이지 : pp. 53-60 (8 pages)

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Background/Aims: Favorable outcomes of potassium-competitive acid blocker (PCAB)-containing eradication therapy have been reported. In fact, tegoprazan, a recently developed PCAB, was presumed to show good eradication efficacy even for resistant Helicobacter pylori. We aimed to investigate the anti-H. pylori efficacy of tegoprazan compared with that of vonoprazan.
Methods: A total of 220 resistant clinical H. pylori isolates were utilized. The anti-H. pylori efficacy of PCABs was determined by evaluating the minimum inhibitory concentrations (MICs) of clarithromycin, fluoroquinolone, metronidazole, and amoxicillin in combination with vonoprazan or tegoprazan by the agar dilution method. The impact of the mutations responsible for resistance development, such as 23S rRNA, gyrA, rdxA, frxA, and pbp1 mutations, was also analyzed.
Results: H. pylori growth was significantly inhibited in a medium containing 1 μg/mL clarithromycin with tegoprazan (128 μg/mL). The MICs of clarithromycin (46.3%), fluoroquinolone (46.7%), metronidazole (55.6%), and amoxicillin (34.5%) against resistant H. pylori isolates improved after tegoprazan administration. Tegoprazan demonstrated more frequent susceptibility acquisition with metronidazole than with vonoprazan (20.6% vs 4.7%, p=0.014). However, there were no significant differences depending on the mutational status of each antimicrobial agent.
Conclusions: Tegoprazan administration may improve the susceptibility of antimicrobial-resistant H. pylori, independent of acid suppression. (Gut Liver 2021;15:53-60)

8Factors Related to Outcomes of Fecal Microbiota Transplantation in Patients with Clostridioides difficile Infection

저자 : Hyuk Yoon , Hyun Ik Shim , Mijin Seol , Cheol Min Shin , Young Soo Park , Nayoung Kim , Dong Ho Lee

발행기관 : 대한소화기내시경학회 간행물 : Gut and Liver 15권 1호 발행 연도 : 2021 페이지 : pp. 61-69 (9 pages)

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Background/Aims: The aim of this study was to evaluate factors related to outcomes of fecal microbiota transplantation (FMT) in patients with Clostridioides difficile infection (CDI) and viability of frozen stock for FMT.
Methods: Clinical data of patients who had received FMT for CDI were prospectively collected. Next-generation 16S rRNA gene sequencing of bacteria was performed from donors' and recipients' stool. Colony-forming units (CFUs) of cultures from frozen stock solutions for FMT were measured at 0, 4, 8, 12, 24, 48 weeks after preparation of the solutions.
Results: In total, 25 FMT procedures were performed in 20 cases (14 fresh and 11 frozen FMT). Forty-five percent of cases involved fulminant CDI. The overall success rate was 55% after the 1st FMT and 75% after the 2nd FMT. The success rate was significantly higher in partially treated CDI than in refractory CDI (100% vs 71.4%; p=0.001). In successful cases only, the decrease in alpha-diversity in the recipient stool microbiomes was recovered after FMT to a level similar to that in donor stools. There was a significant difference in the microbiome composition in pre-FMT recipients' stool between successful and failed cases (p=0.001). The CFUs of frozen solution for FMT did not decrease for 48 weeks in both aerobic and anaerobic cultures.
Conclusions: FMT is highly effective in partially treated CDI but not in refractory CDI. The microbiome differs between failed and successful cases. Frozen stock for FMT is viable up to 48 weeks. (Gut Liver 2021;15:61-69)

9Expression of Chemokine CCL28 in Ulcerative Colitis Patients

저자 : Dong Seok Lee , Kook Lae Lee , Ji Bong Jeong , Sue Shin , Su Hwan Kim , Ji Won Kim

발행기관 : 대한소화기내시경학회 간행물 : Gut and Liver 15권 1호 발행 연도 : 2021 페이지 : pp. 70-76 (7 pages)

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Background/Aims: Ulcerative colitis (UC) is an inflammatory bowel disease for which new serological markers are required. The purpose of this study was to assess the role of the mucosaassociated epithelial chemokine CCL28 in UC.
Methods: The study included 50 patients; of these, 25 were patients with UC, and 25 were healthy controls. The levels of serum CCL28 were analyzed using enzyme-linked immunosorbent assay. CCL28 expression was analyzed by immunohistochemistry (IHC) in 15 representative colon tissues biopsied based on disease activity (UC patients with severe activity, five samples; UC patients with mild activity, five samples; healthy controls, five samples).
Results: The serum CCL28 levels were remarkably higher (p<0.05) in patients with UC (median, 235.7 pg/mL; IQR, 63.8 to 117.2 pg/mL) than in healthy controls (median, 48.9, pg/mL; IQR, 35.9 to 42.0 pg/mL). However, there was no significant difference in serum CCL28 according to disease extent or activity. In contrast, IHC analysis revealed a significant difference in CCL28 consistent with disease status, disease extent, and disease activity.
Conclusions: CCL28 could be useful for diagnosing UC. However, further validations of CCL28 on disease activity and severity are needed. (Gut Liver 2021;15:70-76)

10Long-term Prognosis of Localized Lymphoid Hyperplasia of the Rectum

저자 : Ji Taek Hong , Eun Ran Kim , Sung-wook Park , Ji Won Kim , Sung Noh Hong , Dong Kyung Chang , Young-ho Kim , Jun Hun Cho

발행기관 : 대한소화기내시경학회 간행물 : Gut and Liver 15권 1호 발행 연도 : 2021 페이지 : pp. 77-84 (8 pages)

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Background/Aims: Although localized lymphoid hyperplasia (LLH) of the rectum is occasionally observed, its clinical implications are unclear. This study aimed to investigate the clinical course and significance of LLH of the rectum.
Methods: We identified 65 patients diagnosed with LLH of the rectum using a histopathologic examination and who received follow-up endoscopies between January 2009 and June 2015. Patients with a history of inflammatory bowel disease, lymphoma, familial adenomatous polyposis, or uncontrolled malignancy and patients who underwent scar biopsy after endoscopic resection or surgery were excluded. Endoscopic findings and clinical courses were analyzed.
Results: During the median follow-up of 31 months (interquartile range, 19 to 40 months), 81.5% (53/65) of LLHs of the rectum were resolved. Clinically significant diseases, including ulcerative colitis (UC, n=5) and mucosa-associated lymphoid tissue (MALT) lymphoma (n=1), were diagnosed in 9.2% of patients (6/65). The other six patients showed no significant changes in the lesion (n=3) or a waxing and waning appearance (n=3). According to endoscopic findings, all of the 47 polypoid types showed resolution or waxing and waning patterns. Five of the 11 nodular types (45.5%) developed into UC. One of the seven submucosal tumor (SMT)-like types (14.3%) developed into MALT lymphoma.
Conclusions: LLH of the rectum with persistent symptoms or the endoscopic appearance of the nodular or SMT-like type may lead to clinically significant disease. Risk stratification according to endoscopic findings and careful surveillance are required for these lesions. (Gut Liver 2021;15:77-84)

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