“Evidence-Practice Gap” and How It Applies to H pylori Treatment

There is a well-described “evidence-practice gap” which has been cited to describe the lag between initial discovery and widespread, evidence-based clinical implementation (M Beauchemin et al. ANS Adv Nurs Sci. 2019 Oct-Dec;42(4):307–324); it has been suggested that this gap is typically about 17 years.

I was looking this up after reading a “practice tips” article on H pylori and was surprised at how infrequentlly practitioners follow guidelines for optimal treatment.

M Ventoso, SF Moss. Gastroenterology & Hepatology 2026; 22: 80-86. Open Access! Practice Tips From the Updated Helicobacter pylori Treatment Guidelines 

Background: “The American College of Gastroenterology (ACG) recently published H pylori management guidelines6 with significant updates to the prior recommendations published in 2017.7 Importantly, the 2017 management guidelines relied heavily upon extrapolation from studies performed outside of North America. Since then, new data from US patients have become available that highlights the rising rates of resistance of commonly used antibiotics for treatment of H pylori.”

Key points:

  • Bismuth Quadruple Therapy Is First Line and Should Be Optimized” (see below). A 14-day course is recommended (except when using Pylera which is a 10 day treatment).
  • “3 new regimens have received US Food and Drug Administration (FDA) approval for H pylori therapy, each based on high levels of gastric acid inhibition. “
  • “The first is a combination tablet of rifabutin with amoxicillin and omeprazole (Talicia, RedHill Biopharma), given in daily doses of 150 mg, 3 g, and 120 mg, respectively. If the combination tablet is not available, generic equivalents can be substituted at similar doses (omeprazole 40 mg and amoxicillin 1 g each 3 times daily). Because the lowest available dose of generic rifabutin is only 150 mg, the best option is likely 150 mg twice daily”
  • “The second regimen is based on vonoprazan (Voquezna, Phathom Pharmaceuticals), the first potassium-competitive acid blocker (P-CAB) approved in the United States. substituting the P-CAB vonoprazan for lansoprazole in clarithromycin triple therapy produced higher eradication rates (81% compared with 69%). Similar statistically high rates (77%) were achieved with a dual vonoprazan-amoxicillin combination in the same trial, leading to FDA approval of both the triple and dual regimens14
  • For “both rifabutin- and vonoprazan-containing regimens use amoxicillin and cannot be used in the confirmed penicillin-allergic patient. For patients with unproven penicillin allergy (approximately 10% of the US population), allergy testing is recommended”
  • Use Clarithromycin or Levofloxacin Only If Antimicrobial Susceptibility Is Confirmed
  • “The majority of practitioners continue to use clarithromycin-based triple therapy and have not followed the 2017 ACG H pylori guidelines …It is striking that clarithromycin-PPI triple therapy still dominates the US market, comprising greater than 80% of all treatments in 2016 to 2019.11 Notably, in approximately half of the cases where clarithromycin-PPI triple therapy failed, exactly the same prescription was given a second time.11 Thus, a massive implementation gap exists.”

My take:

  1. While this article focuses on adult guidelines, there are similar issues in pediatrics. There is an even greater need for research involving children with H pylori. As vonoprazan appears to improve eradication rates, more guidance is needed regarding drug regimens with vonoprazan in kids.
  2. I frequently see patients who have received empiric clarithromycin-based therapy. Based on this article, I should be less surprised that this is so commonplace.

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.

QI Project: Increasing H Pylori Eradication

KR Arellanos et al (Senior Author S Bonilla). JPGN Reports. 2026;7:19–27. Standardizing a protocol for Helicobacter pylori gastric biopsy culture: From implementation to sustained practice

Background: “The availability of antibiotic susceptibility data is essential for understanding local and regional resistance patterns and for informing future guidelines on optimal treatment regimens for children.” This quality improvement project report documents how “using a standardized checklist, in combination with educational initiatives for staff physicians and collaborative efforts with endoscopy and laboratory teams, were effective strategies to increase the use of gastric biopsy culture as a diagnostic tool for H. pylori infection and, to a lesser extent, to improve culture yield in patients with positive histology.”

Key steps:

  1. Standardized checklist for biopsy collection used by nurses
  2. Standardized transport protocol
  3. Prompt refridgeration/transportation
  4. Using a single lab for testing (Mayo clinic)

Key findings:

  • There was a consistent increase in culture positivity for H pylori and this was associated with improved eradication rates
  • Overall, antimicrobial resistance was highest for metronidazole (27.5%) and clarithromycin (18.7%), and lower for rifampin (12.2%), levofloxacin (10.1%), and amoxicillin (4.3%). Only one isolate showed resistance to tetracycline

Discussion: “Among the various interventions implemented during the QI project, the one that appears to have contributed most significantly to the dramatic improvement in culture yield among patients with H. pylori-positive histology was the consolidation of specimen processing to a single specialty laboratory [Mayo clinic].” Specific logistics included using a simple sterile container with saline-moistened tissue for collection and sending samples to specialty lab on the same day as collection.

My take: During this project, there was improved use of gastric culture and in culture yield. This resulted in meaningful improvement for patients. However, without clinical leadership to implement these changes, there will continue to be suboptimal eradication rates at other centers.

Related blog posts:

Probiotics in Addition to Standard Therapy Associated with Improved Eradication of H pylori

DC Deza et al. AJG 2025. 120:p 2644-2659Probiotics Prescribed With Helicobacter pylori Eradication Therapy in Europe: Usage Pattern, Effectiveness, and Safety. Results From the European Registry on Helicobacter pylori Management (Hp-EuReg) Thanks to Ben Gold for this reference.

Methods: Prospective European registry with 36,699 treatments were recorded, where 8,233 (22%) were prescribed with probiotics. The analysis of the effectiveness of probiotics was restricted to those receiving first-line therapy.

Key findings:

  • Overall, the eradication rate was 90.6% with probiotics and 86.1% without probiotics.
  • With quadruple therapy, the eradication rate was 93.1% with probiotics and 89.3% without probiotics

Discussion Points:

  • “The prevalence of H pylori infection remains close to 45% in the European population”
  • The population receiving probiotics may have been expected to have a higher risk of eradication failure (eg. antibiotic resistance and more prior treatments) and/or higher expectations of adverse effects
  • This was NOT a randomized study which limits a more definitive conclusion on the effectiveness of adding a probiotic

My take: In highly-motivated families, probiotics may be worthwhile as part of an H pylori eradication regimen. This could, of course, necessitate changes in nomenclature. Would quadruple therapy with probiotics be called 5-drug (quintuple) treatment?

Related blog posts:

H pylori:

Probiotics:

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: