Helicobacter Pylori 2019 Review

A recent review (SE Crowe. NEJM 2019; 1158-65) provides a succinct summary of current H pylori management.

A couple of key points:

  • It is essential to test for cure after treatment 1 month afterwards
  • If retreatment is needed, use an alternative regimen
  • In the discussion of treatment, Dr. Crowe does NOT emphasize quadruple therapy except in individuals with a clarithromycin resistance probability of >25% (based on geographic incidence rates) or prior macrolide use.  She notes that in some populations that clarithromycin-based triple therapy had similar effectiveness as bismuth-based quadruple-based therapy.  Table 2 lists the 7 ACG approved treatment regimens.
  • It is noted that U.S. clarithromycin-resistance is between 21-30%.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

It is Getting Harder to Treat H pylori -Here’s Why

In a recent study (A Savoldi et al. Gastroenterol 2018; 155: 1372-82, editorial pg 1287), the authors conducted a systematic review and meta-analysis to examine the prevalence of antibiotic resistance to Helicobacter pylori. The authors identified 178 studies with 66,142 H pylori isolates. Tables 2 & 3 provide comprehensive data.

Key points:

  • In the Americas region, primary resistance to clarithromycin, metronidazole, levofloxacin and amoxicillin was 10%, 23%, 15%, and 10% respectively.
  • In the European region, primary resistance to clarithromycin, metronidazole, levofloxacin and amoxicillin was 18%, 32%, 11%, and 0% respectively.

Antibiotic resistance is increasing: 

  • In the Americas region, resistance in 2006-2008 compared to 2012-201 for clarithromycin, & metronidazole: 11%–>20%, 26%–>29% respectively.
  • In the European region, resistance in 2006-2008 compared to 2012-201 for clarithromycin, & metronidazole: 28%–>28%, 38%–>46% respectively.
  • “The resistance rates to clarithromycin, metronidazole, and levofloxacin have increased over time in all WHO regions.”  Other regions with data in study included Eastern Mediterranean, Southeast Asia, and Western Pacific.
  • In the study, the authors also “describe a clear significant association between antibiotic resistance and treatment failure.”

In their discussion, the authors note that the incidence of gastric cancer is higher in areas with increased antibiotic resistance.  Though there has been a decline in gastric cancer, “based on our data, we can hypothesize that this trend in reduction is expected to revert soon because available treatment can no longer guarantee a satisfactory eradication rate.”

From editorial:

  • H pylori is not one of those bacteria in which resistance develops as an epidemic by horizonatal transfer of mobile genetic elements…Resistance in H pylori only occurs unevenly by mutations…Fortunately, resistance occurs “very seldomly for …amoxicillin and tetracycline.”
  • Treatment failure is “almost 7 times greater (6.97) when the strain is clarithromycin resistant and even greater (8.18) when the strain is levofloxacin resistant.” Resistance to metronidazole confers a lesser degree of treatment failure risk: OR 2.52.

My take: This study provides some sobering news about H pylori prevalence and how it is becoming more difficult to treat.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

Pooled Prevalence of resistance to clarithromycin (2006-2016). This is from Figure 2. Sections B & C (not shown) provide similar graphic info for metronidazole and levofloxacin

The Rise of Eosinophilic GI Diseases –Not Likely Connected to Helicobacter Pylori

A recent prospective case-control study (J Molina-Infante et al. Am J Gastroenterol 2018; 113: 972-9 -thanks to Ben Gold for this reference) examined the potential connection between Helicobacter pylori and eosinophilic GI diseases.  They examined 808 individuals (404 cases of eosinophilic esophagitis [EoE], 404 controls). Key findings:

  • H pylori prevalence was not different between cases and controls (37% vs. 40%, odds ratio 0.97).  The authors conclude that H pylori which has declined in prevalence globally is not inversely associated with EoE as had been suggested in some previous reports

In an associated editorial, (pg 941-4), the authors note that there has been a dramatic increase in atopic diseases over the past 30 years.  One hypothesis has suggested that these epidemiologic changes are related to a changing microbiome.  This in turn may be related to frequent antibiotic usage.  An example of the proliferation of antibiotics: “20-25% of Swedish adults receive an antibiotic prescription annually.”

While H pylori may be a biomarker associated with poor hygiene/less antimicrobial exposure, it does not appear to be directly related to EoE.  The authors indicate that until we have a better understanding, “in the meantime attention to healthier diets and minimizing antibiotic exposure may optimize public health in terms of atopic disease risk.”

My take: Since our genetics do not change quickly, the dramatic changes in disease frequency of conditions like EoE and Crohn’s disease must be influenced by environmental exposures.  How to lower the risk of these conditions remains uncertain.

Related blog posts:

Not a joke –WIFI hotspot at Sunshine Meadows, Banff National Park

How Helicobacter pylori Survives in the Stomach

A recent basic science study (P Morey et al. Gastroenterol 2018; 154: 1391-1404) explains one of the mechanisms whereby Helicobacter pylori survives in the stomach.

The researchers used MKN45 gastric epithelial cells and human gastric cells obtained from patients undergoing gastric resections and exposed them to H pylori strains. They did additional studies in infected mice.

This report has a number of cool figures demonstrating that H pylori blocks the assembly of interferon and other cytokines.  Infected gastric cells were depleted of cholesterol which rendered them unable to respond properly to inflammatory signals from immune cells.  H pylori is able to decrease inflammation at sites of colonization while inducing inflammation in adjacent noninfected epithelium.  The authors note that patients with increased serum cholesterol (especially LDL) are at increased risk for severe H pylori gastritis.

Big Creek Greenway, Alpharetta

NASPGHAN Postgraduate Course 2017 (Part 2): Celiac, Fad Diets, and H pylori

Over the next 2 weeks or so, I am posting my notes/pictures from this year’s annual meeting.  This post reviews the 2nd module from the postgraduate course.

This blog entry has abbreviated/summarized these presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Here is a link to postgraduate course syllabus: NASPGHAN PG Syllabus – 2017

Celiac Disease Diagnosis: ESPGHAN vs. NASPGHAN Guidelines

Michelle Pietzak   Children’s Hospital of Los Angeles

This lecture started with a succinct history of celiac disease, including discussion of the banana diet and the observation that wheat deprivation during World War II was associated with improvement in children with celiac disease. The sequential diagnostic recommendations of ESPGAN and NASPGHAN were reviewed.

Key points:

  • ESPGHAN 2012 guidelines separated children in two groups: symptomatic and asymptomatic.  The guidelines indicated that symptomatic children with high titer serology (TTG IgA >10-fold ULN and positive EMA) could be diagnosed without an intestinal biopsy.
  • ACG 2013 Guidelines: TTG IgA preferred serologic test if over age 2 years,  TTG IgA along with deamidated gliadin (IgG and IgA) recommend if younger than 2 years. Even if negative serology, a biopsy was recommended if significant suspicion of diagnosis.
  • NASPGHAN, AGA, ACG all recommend small bowel biopsy to confirm this lifelong condition
  • The speaker did not critically discuss the Leonard et al study suggesting that 19% of individuals had persisting enteropathy on a gluten fee diet (see previous posts below)
  • Jimmy Fallon: “10% of the population is allergic to gluten and 90% are tired of hearing about it”

Related posts:

Fad Diets: The Good, the Bad, and the Just Plain Ugly

Mark Corkins      University of Tennessee Health Science Center

Key points:

  • Fad diets driven in part by obesity
  • Gluten-free diet is the most trendy, ~30% of U.S. adults are ‘limiting’ gluten, though most do not understand what gluten is.  “Wheat Belly” book by Dr. William Davis has been influential despite lack of data.
  • According to marketing report, 35% who consumer gluten limited diet have no reason for this, 26% for ‘healthier option,’, 19% for ‘digestive health,’, 13% for weight loss, 8% for gluten sensitivity
  • Recommends: choosemyplate.gov. These feeding guidelines have been developed by nutrition experts.

Update on H pylori

Nicola Jones    Hospital for Sick Children (Toronto)

  • Reviewed current recommendations based on ESPGHAN/NASPGHAN 2016 recommendations.
  • The speaker indicates that upper endoscopy is recommended for initial diagnosis of H pylori but testing is not recommended for functional abdominal pain.  The lecture did not address the issue that there can be an overlap in the presentations of these disorders.
  • Adherence is crucial for adequate eradication
  • Newer studies show improved eradication rates for quadruple therapy (bismuth-based) & in U.S. this is recommended as first-line treatment unless resistance patterns are known (which could allow for triple therapy)

 

Updated Pediatric Helicobacter Pylori Guidelines

Joint ESPGHAN/NASPGHAN guidelines (NL Jones et al. JPGN 2017; 64: 991-1003) have been published.  Overall, these guidelines cover a great deal of information.  It is interesting that these guidelines provide some conflicting advice with recommendations for adults.

  • Some recommendations:
    The authors recommend against diagnostic testing H pylori in children with functional abdominal pain
  • The authors recommend against using antibody-based tests from blood, urine, or saliva.
  • The authors recommend noninvasive testing for H pylori when investigating chronic immune thrombocytopenic purpura (ITP)
  • First line therapy recommendations if sensitivity is unknown: High-dose PPI-Amoxicillin-Metronidazole for 14 days OR Bismuth-based quadruple therapy (in children less than 8 years, quadruple therapy would be bismuth, PPI, amoxicillin and metronidazole; in older children it is recommended to substitute tetracycline for amoxicillin).  Specific dosing is given in this report (Table 3 and Table 4)
  • The authors recommend assessing for infection eradication at least 4 weeks after completion of therapy

My take: I favor quadruple therapy for most patients (see adult guidelines below) until sensitivities can be more easily obtained.  If you know of a reliable lab to obtain culture sensitivities, please let me know.

Related blog posts:

Adult Guidelines:

Other related posts

ACG Guideline for Helicobacter Pylori

Link: ACG Clinical Guideline: Treatment of Helicobacter pylori Infection

The American Journal of Gastroenterology , (10 January 2017) | doi:10.1038/ajg.2016.563

William D Chey, Grigorios I Leontiadis, Colin W Howden and Steven F Moss

Helicobacter pylori (H. pylori) infection is a common worldwide infection that is an important cause of peptic ulcer disease and gastric cancer. H. pylori may also have a role in uninvestigated and functional dyspepsia, ulcer risk in patients taking low-dose aspirin or starting therapy with a non-steroidal anti-inflammatory medication, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura. While choosing a treatment regimen for H. pylori, patients should be asked about previous antibiotic exposure and this information should be incorporated into the decision-making process. For first-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who reside in areas where clarithromycin resistance amongst H. pylori isolates is known to be low. Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole. When first-line therapy fails, a salvage regimen should avoid antibiotics that were previously used. If a patient received a first-line treatment containing clarithromycin, bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options. If a patient received first-line bismuth quadruple therapy, clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options. Details regarding the drugs, doses and durations of the recommended and suggested first-line and salvage regimens can be found in the guideline.

My take: Recent draft guidelines from our pediatric group, NASPGHAN, suggested that triple therapy, in addition to quadruple therapy, would still be considered a first-line approach.  When the NASPGHAN report is completed/published, it will be of interest to see whether this discrepancy persists.

Related blog posts:

screen-shot-2017-01-10-at-7-53-16-pm