5 Rights and H pylori Treatment

For medication administration, there are five “rights” that are needed for optimal results:

  • Right drug
  • Right dose
  • Right route (e.g., oral, intravenous, topical)
  • Right patient
  • Right time 

The recent article below highlights the fact that the “right drug” for H pylori can be dependent on resistance patterns. Previous articles (see below) have shown that the right dose is equally-important to improve cure rates.

C Chan et al. J Pediatr Gastroenterol Nutr. 2025;81:1133–1141. Antimicrobial susceptibility-guided treatment is superior to empiric therapy for Helicobacter pylori infection in children

Methods: Retrospective study with 218 children who had histologically-proven H pylori infection.  Susceptibility-guided treatment (SGT) was given to 123 and empiric therapy (ET) to 95. Testing for susceptibility was via a send-out assay to an outside specialty laboratory (Mayo Clinic Laboratories).

Key findings:

  • Eradication success was significantly higher in the SGT group (89.4%,110/121) compared to the ET group (70.2%, 66/94) (p < 0.001).
  •  Amoxicillin resistance was strongly associated with failure (27.3% vs. 0.9%, p = 0.002), as was dual clarithromycin-metronidazole resistance (36.4% vs. 8.2%, p = 0.018).

My take: This study shows the huge improvement when therapy is adjusted based on known susceptibility.

Related blog posts:

Amicalola Falls State Park

Also, more on changes to CDC website:

Benjamin Mazer, The Atlantic; 11/21/25: Open Access! Do Childhood Vaccines Cause Tornadoes? It hasn’t been ruled out (Related blog post: CDC Website Changed to Include False Claims About Autism and Vaccines)

Global Evidence of Gastric Cancer Prevention with Helicobacter pylori Eradication

Several recent articles have confirmed the benefits of H pylori eradication on reducing the risk of gastric cancer. This is in both Western and Eastern populations.

In this retrospective study from Nordic countries (Denmark, Sweden, Norway, Finland, and Iceland), researchers followed outcomes among ~700,000 people treated for H. pylori infection. The incidence of gastric adenocarcinoma was twice that of the general population in the first 5 years after treatment, likely reflecting H. pylori–related carcinogenesis that already was underway, but after 11 years, the incidence fell to that of the general population and remained there.

Discussion points:

  • The results of this study from 5 entire Western countries are in line with systematic reviews from Asian populations, indicating that H pylori eradication reduces the risk of gastric cancer
  • In addition, it has been proposed that eradication of H pylori might increase the risk of esophageal adenocarcinoma, but our recent study based on the NordHePEP found no such increase (Ref: Gastroenterology. 2024; 167:485-492.e3)

In this population-based study with more than 900,000 individuals, gastric cancer incidence and mortality rates were significantly lower in H pylori-treated individuals than in the general population.

In this meta-analysis of 11 randomized trials and 13 cohort studies researchers compared outcomes in treated and untreated H. pylori–positive adults. In both groups of studies, gastric cancer incidence was 40% lower in people who underwent H. pylori eradication. All but two of these studies were from eastern Asia.

 “In 2025, the IARC Working Group has issued a new report reaffirming H pylori eradication as a globally actionable and cost-effective intervention for the primary prevention of GC.18…Also, addressing the global public health challenge of antibiotic resistance remains essential, necessitating the development of susceptibility-guided or empirically optimized regimens tailored to local resistance patterns.

My take (borrowed from the commentary): “Despite the challenges, collectively, the emerging evidence from diverse populations reinforces the significant benefits of H pylori eradication in reducing GC incidence and mortality. These findings continuously support that H pylori eradication remains an effective preventive strategy across demographic settings, highlighting its relevance as a critical public health measure globally.”

Related blog posts:

Elevated Fecal Calprotectin Levels in Pediatric Patients with H pylori Infection

P Villalba-Davila et al. J Pediatr Gastroenterol Nutr. 2025;80:617–622 Helicobacter pylori infection is associated with significant elevations to fecal calprotectin, systemic inflammatory markers

In this retrospective study from a high immigrant density community, patients aged 6–18 years old who had an fecal calprotectin (FC) level within 6 months prior to EGD and who were tested for HP infection were included in the study. 

Key findings:

  • Of 129 patients, 37 (28.7%) tested positive for HP infection.
  • The mean FC level was significantly elevated in HP-positive patients (241.2) as compared with HP-negative patients (88.1) (p < 0.001)
  • HP-positive patients were also found to have small but notably higher elevations of CRP and ESR levels

My take: This study confirms what I have seen in my own practice. Patients with H pylori frequently have elevated calprotectin levels. Checking stool for H pylori may help avoid some colonoscopies. H pylori infection, however, can be present in patients with inflammatory bowel disease as well.

Related blog posts:

Phang Nga Bay, Thailand

Key Advances in 2024: An Overview from GutsandGrowth (Part 3)

This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

Dr. Benjamin Gold: 2024 Pediatric H pylori Guidelines (Part 2)

We had a brilliant lecture given to our group by Dr. Benjamin Gold. I have had the good fortune of getting to know Ben and working alongside Ben for more than 15 years. Most readers of this blog are very familiar with Dr. Gold who is a leader in our field.

My notes below may contain errors in transcription and in omission.

Guidelines:

  • Bismuth-based quadruple therapy recommended when antimicrobial sensitivity testing (AST) is not available
  • Routine use of CLO test is NOT recommended during endoscopy
  • Routine testing for H pylori is NOT recommended for children with recurrent abdominal pain
  • Stool PCR testing is NOT recommended
  • Test for cure should be done at 6-8 weeks after completion of treatment

During endoscopy at CHOA in which H pylori is suspected, complete a microbiology form and ask for a culture to arrange for resistance testing.  Submit a sample (or multiple) in a sterile tube/cup.  Completed results will include clarithromycin sensitivity.  Additional testing for other antibiotic resistance can be requested subsequently.  Testing can be done with paraffin block as well.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Dr. Benjamin Gold: 2024 Pediatric H pylori Guidelines (Part One)

We had a brilliant lecture given to our group by Dr. Benjamin Gold. I have had the good fortune of getting to know Ben and working alongside Ben for more than 15 years. Most readers of this blog are very familiar with Dr. Gold who is a leader in our field.

My notes below may contain errors in transcription and in omission.

.Key points:

  • While H pylori prevalence has decreased, it is becoming more difficult to treat
  • Knowing if there is clarithromycin resistance in individuals with H pylori infection is most likely to impact treatment success. Metronidazole resistance can often be overcome with adequate dosing
  • H pylori is an infectious disease with GI manifestations (rather than a GI disease).  It needs to be treated as such, using tools like antimicrobial sensitivity
  • Improving water supply in endemic areas reduces reacquisition of infection
  • Transmission can occur from one generation to the next.  Dr. Gold (& coauthors) has published a study showing transmission from grandfather to mother to child using DNA fingerprinting
  • Eradication of H pylori lowers the risk of developing gastric cancer
  • Vonoprazan has been an effective part of treatment in adults. Pediatric studies are underway

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Getting Rid of H pylori Does Not Increase the Risk of Esophageal Adenocarcinoma

A-K Wiklund, et al. Gastroenterol 2024; 167: 485-492. Risk of Esophageal Adenocarcinoma After Helicobacter pylori Eradication Treatment in a Population-Based Multinational Cohort Study

Background: Helicobacter pylori infection is associated with a decreased risk of esophageal adenocarcinoma, and the decreasing prevalence of such infection might contribute to the increasing incidence of this tumor. For this reason, the authors examined the hypothesis that eradication treatment of H pylori increases the risk of esophageal adenocarcinoma.

Methods: Using national registries with Nordic population adults (≥18 years, n=661,987) receiving H pylori eradication treatment from 1995–2018, the authors evaluated 5,495,552 person-years after eradication treatment.

Key findings:

  • The standardized incidence ratios (SIR) did not increase over time after eradication treatment, but rather decreased and was 0.73 at 11–24 years after treatment
  • The overall SIR of esophageal squamous cell carcinoma, calculated for comparison, showed no association (SIR = 0.99)

My take: Eradication of H pylori lowers the risk of gastric cancer. This study shows that treatment does NOT result in an unintended consequence of increasing esophageal cancer.

Related blog posts:

Helicobacter Pylori Stool Susceptibility in Children –How Good Is It?

S Bonilla et al. JPGN 2023; 77: 623-627. Helicobacter pylori Antimicrobial Resistance Using Next-Generation Sequencing in Stool Samples in a Pediatric Population

Background: Stool H pylori testing “has become available and is based on the detection of mutations in H pylori genome associated with antimicrobial resistance and corresponds well with resistance determined by culture”

Methods: The authors obtained stool susceptibility testing using a novel NGS-based analysis and compared results with the current “gold standard” of gastric biopsy culture via agar dilution in 20 pediatric patients with evidence of H pylori in gastric biopsies. Stool samples were sent to American Molecular Laboratories (description in supplemental material). Gastric samples were sent to Mayo Laboratories.

Key findings:

  • Stool NGS-based antimicrobial susceptibility analysis was highly concordant with agar dilution (gastric biopsies) for no resistance (100% agreement), as well as clarithromycin, levofloxacin, and amoxicillin resistance (100%, 67%, and 100% agreement, respectively) but not concordant for metronidazole in our cohort of patients.
  • 35% of patients had antibiotic resistance identified

My take: Since H pylori is difficult to treat, identifying susceptibility patterns can be very helpful. This study shows that stool specimens have good agreement with gastric biopsy testing. While the results for metronidazole are not as good, resistance to metronidazole can often be overcome as part of multidrug regimens.

Lisbon and the Tegas River

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Synergistic Dangers: Helicobacter Pylori and Cancer Genes

Y Usui et al. NEJM 2023; 388: 1181-1190. Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer

Background: Gastric cancer is the fifth most common neoplasm and the fourth leading cause of death from cancer worldwide.1 Helicobacter pylori has been classified as a group I carcinogen and is an environmental risk factor for gastric cancer.2 Although H. pylori infection affects more than half the world population

Methods: This study evaluated the association between germline pathogenic variants in 27 cancer-predisposing genes and the risk of gastric cancer in a sample of 10,426 patients with gastric cancer and 38,153 controls from BioBank Japan. This retrospective study also assessed the combined effect of pathogenic variants and H. pylori infection status on the risk of gastric cancer and calculated the cumulative risk in 1433 patients with gastric cancer and 5997 controls from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC).

Key findings:

  • Germline pathogenic variants in nine genes: (APCATMBRCA1BRCA2CDH1MLH1MSH2MSH6, and PALB2) were associated with the risk of gastric cancer.
  • At 85 years of age, persons with H. pylori infection and a pathogenic variant had a higher cumulative risk of gastric cancer than noncarriers infected with H. pylori (45.5% vs. 14.4%).
  • Limitation: The study population was from East Asia and thus, the findings may be different in other populations.

My take: H. pylori infection has a synergistic effect in increasing the risk of gastric cancer in individuals with germline pathogenic variants in homologous-recombination genes. To minimize the risk of gastric cancer, H pylori eradication is important; however, it is especially in those with cancer-predisposing variants.

From NEJM Twitter Feed

Related blog posts:

Understanding FDA Approval of Vonoprazan-Based Therapies for Helicobacter Pylori

Pharmacy Times (5/4/22): FDA Approves Pair of Vonoprazan Treatments for Helicobacter Pylori Infection

“The (FDA) has approved 2 vonoprazan-based medications for the treatment of Helicobacter pylori (H. pylori) infection.

Phathom Pharmaceuticals announced the approvals of both the Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin) based on positive safety and efficacy data from the phase 3 PHALCON-HP trial.”

WD Chey et al. Gastroenterol 2022; 163: 608-619. Open Access! Vonoprazan Triple and Dual Therapy for Helicobacter pylori Infection in the United States and Europe: Randomized Clinical Trial

Key findings from this randomized, controlled trial with treatment-naive 1046 adults:

  • In all patients, vonoprazan triple and dual therapy were superior to lansoprazole triple therapy (80.8% and 77.2%, respectively, vs 68.5% (both superior)
  • In patients with clarithromycin resistance, vonoprazan triple therapy was effective in 65.8%, dual therapy in 69.6%, vs lansoprazole triple therapy 31.9% (both superior)
  • Vonoprazan increases intragastric pH rapidly “and maintains it to a greater degree than PPI; this has been associated with higher H pylori eradication rates” (in prior studies as well)

The associated editorial: CA Fallone (Open Access!) The Current Role of Vonoprazan in Helicobacter pylori Treatment

Based on this new information, the author proposes the treatment algorithm below and notes that “the role of increased acid suppression by PPI substitution with vonoprazan should be examined in other H pylori regimens.” The author favors bismuth quadruple therapy in those with clarithromycin resistance as non-bismuth quadruple therapy utilizes an unnecessary antibiotic (clarithromycin).

Other points:

  • Metronidazole resistance is fairly common, but bismuth quadruple therapy can overcome much of the metronidazole resistance
  • Levofloxacin resistance is quite high in certain regions and should only be used with caution, given recent warnings from the US Food and Drug Administration of aortic rupture in susceptible individuals
  • Rifabutin can cause some bone marrow suppression

My take: With the more widespread availability of susceptiblity testing (beyond clarithromycin), I anticipate more targeted treatments. At the same time, vonoprazan-based treatments are likely to be important in increasing eradication rates.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.