new H Pylori treatment guidelines

 the American College of Gastroenterology (ACG) just published their new H Pylori treatment guidelines (see H pylori treatment JAMA2026 in dropbox, or doi:10.1001/jama.2026.0663)

Details:

-- the American College of Gastroenterology updated their previous guideline suggestions on H Pylori treatment based on the increasing resistance of H Pylori bacteria to the prior meds

-- these recommendations apply to patients at least 18yo who reside in North America

    -- the guidelines prioritized studies done in the US that assessed both treatment-naive and treatment-experienced patients

-- their concern is that H pylori is associated with the development of gastritis, peptic ulcers, and gastric cancer

-- they incorporated the use of rifabutin and the more potent gastric acid suppressant vonoprazan

    -- of the overall 11 recommendations, 5 were for treatment-naive patients (1 strong recommendation based on moderate quality of evidence (QOE)

    -- the remaining 4 conditional recommendations were based on either low or moderate QOE

    -- and 6 were for patients previously receiving treatment (all conditional recommendations were based on either low or very low QOE)

-- The guideline did not address diagnostic testing because the recommendations have not changed from prior guidelines

Recommendations:

-- For treatment-naive patients with H pylori infection, bismuth quadruple therapy (BQT) for 14 days is recommended as first-line treatment (strong recommendation; moderate quality of evidence [QOE]).

    -- when BQT is not an option, recommend rifabutin triple therapy (conditional recommendation; low QOE)

    -- or use a potassium-competitive acid blocker (PCAB; eg, vonoprazan) dual therapy (conditional recommendation; moderate QOE)

-- For treatment-naive patients with H pylori, empirical use of regimens containing clarithromycin are not recommended (though there are 2 that snuck into the list)

    --however, if no first-line treatment is available, PCAB triple therapy is suggested over proton pump inhibitor (PPI) triple therapy (conditional recommendation; moderate QOE).

-- For patients with persistent H pylori infection who received PPI triple therapy rather than BQT, BQT is suggested (conditional recommendation; low QOE).

-- For patients with persistent H pylori infection who have received BQT, rifabutin triple therapy is suggested

Commentary: 

-- H pylori infection is unbelievably common, affecting >50% of world's population, and is the most common chronic bacterial infection in the world

-- the above recommendations comment that it can cause" chronic gastritis, peptic ulcers, and gastric cancer"

    -- but there are many, many more bad effects to H Pylori than that, including increased diabetes risk (https://gmodestmedblogs.blogspot.com/2024/09/h-pylori-infection-increases-diabetes.html ); many dermatologic manifestations including chronic pruritus and urticaria (and i have had a couple of patients whose chronic pruritus and chronic urticaria for years resolved with H Pylori treatment (for more on the dermatologic associations, see hpylori and skin disease amjclinderm2002 in dropbox, or Wedi B and Kapp A. Am J Clin Dermatol 2002; 3(4): 273-282), increased risk of GI bleeding when taking NSAIDs or aspirin, increased risk of ITP, and MALT (gastic mucosa-associated lymphoid tissue lymphoma)

        -- there are a few studies showing that people with asymptomatic H Pylori infection then put on NSAIDs or low dose aspirin have a markedly increased risk of a GI bleed, including severe bleeds: https://gmodestmedblogs.blogspot.com/2015/05/h-pylori-and-nsaids-increased-gi.html

        -- there are also variants of H Pylori associated with worse outcomes (Cag-A  and VacA are more carcinogenic, the latter being associated with colon cancer). ??is the increased incidence of colon cancer at younger ages related in part to the VacA variant??

    -- however, gastric cancer is the biggest issue, with 80-90% of cases globally attributed to H pylori infection; H Pylori is now considered a carcinogen by the NIH: http://gmodestmedblogs.blogspot.com/2022/03/carcinogen-update-now-including-h-pylori.html  

-- though this article is about therapies for H pylori, it is important to point out that universal testing seems to be appropriate:

    -- it is, as noted above, the most common chronic bacterial infection in the world

    -- it can be completely asymptomatic, yet detection and treatment in many studies has found a decrease in subsequent gastric cancer incidence as well as many of the other associated conditions

    -- a few studies in the US have found that H Pylori incidence may be as high as 30+% of the population:

        -- a VA study found this high rate of H Pylori and confirmed that treating asymptomatic people led to decreased gastric cancer by 76%:  https://gmodestmedblogs.blogspot.com/2023/06/h-pylori-common-in-us-veterans.html. this blog cites other studies as well, including a NHANES study finding a 32.5% prevalence

    -- i have found many cases of H Pylori infection in Boston in patients who have never left the US, including a patient with steroid-resistant ITP who was on the docket to receiving a splenectomy when an article in the Lancet found that patients with asymptomatic ITP were often cured with H Pylori treatment; he received the treatment and (shockingly) had complete resolution of his ITP beginning within days of starting the H Pylori treatment (subsequent hematology guidelines have noted the relationship of H Pylori with ITP)

-- these guidelines were specifically for "outpatients aged 18 years or older with H Pylori infection, with recommendations prioritized for persons residing in North America"

    -- but, but, but there are a quite large number of people in the US who come from other countries, and, though the epidemiology of H Pylori has many knowledge gaps, it seems that people who have H pylori are infected as children and that treatment of H Pylori is associated with significant resistance to reinfection: http://pmc.ncbi.nlm.nih.gov/articles/PMC8133036/

    -- these guidelines are based on antibiotic resistance patterns in the US (which do vary from area to area)

    -- the issue for many of my patients is that many are from the Cape Verdean islands where H Pylori and gastric cancer are prevalent; there has been testing done there that shows no H Pylori resistance to amoxicillin and clindamycin. i have used the old triple therapy of PPI/amoxicillin/clarithromycin with very high success rates

    -- and, as known in several studies (including an upcoming blog on the long-term effect of antibiotics on the gut microbiome, up to 8 years), there are many individuals in the US who have not taken antibiotics at all. so, they should also be susceptible to the old triple therapy

-- these recommendations strongly support their BQT recommendations as the first-line treatment for patients who are treatment-naive. this brings up a few issues:

    -- BQT does involve taking the bismuth 4x/day, which may well lead to medication nonadherence (several older studies have found that once-a-day meds have the best adherence, with decreasing adherence tracking with increased dosing and the lowest with four-times-a-day

    -- this also involves taking metronidazole, which a few years ago was felt to add adverse effects (GI, etc) without much benefit, perhaps related the very high metronidazole resistance rate (a 2022 study in the US found metronidazole resistance in 69% of patients vs 22% resistant to clarithromycin: https://gmodestmedblogs.blogspot.com/2022/11/h-pylori-resistance-patterns-in-us.html

        -- in a Rhode Island study, if patients had at least one other antibiotic to which the H Pylori was sensitive, they had exceptionally high cure rates. This suggests that metronidazole may not really provide any clinical effectiveness if the other antibiotics work. This finding of little metronidazole benefit has been found in other studies using other methods of assessing metronidazole resistance: see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905086/ and http://gmodestmedblogs.blogspot.com/2022/11/h-pylori-resistance-patterns-in-us.html .

            -- and all of the recommended H Pylori regimens above other than the BQT do not include metronidazole

    -- this, and other recommendations above minimize the use of clarithromycin, since H pylori bacteria are increasingly resistant to the (overused) macrolide antibiotics. a study done years ago found that sequential H Pylori therapy works very well even if there is documented clarithromycin resistance by using sequential therapy, which is a bit more complex, employing one week of PPI plus amoxicillin 1 gram twice a day followed by clarithromycin 500mg plus metronidazole 500mg plus PPI twice a day. this therapy may have a higher cure rates than the BQT therapy: https://gmodestmedblogs.blogspot.com/2016/10/h-pylori-regimens-stratified-by.html

        -- sequential therapy works even with documented clarithromycin resistance, with 89% of clarithromycin-resistant strains responding vs 29% responding with standard therapy 

            -- the posited mechanism for resistance is that H pylori had developed efflux channels for clarithromycin that rapidly removes the drug from the bacteria; amoxacillin (as a penicillin) alters the structure of the cell membrane, prevents this effective clarithromycin efflux, and thereby decreases the resistance. (see Ann Intern Med 2007; 146:555-563, and http://gmodestmedblogs.blogspot.com/2013/11/h-pylori-therapy-sequential-vs-standard.html and https://gmodestmedblogs.blogspot.com/2023/01/h-pylori-antimicrobial-resistance-in.html)

    -- the above recommendations consistently promote a full 14 day course of antibiotics (appropriate, based on many studies) and waiting 4 weeks after H Pylori treatment (appropriate, to assess the test-of-cure lab tests (some people were doing 2 weeks in the US/Europe was in the 4-week camp). this recommendation is based on "expert opinion", and includes test-of-cure testing by urea breath test, fecal antigen test or biopsy-based testing

    -- the guidelines do support the welcome addition of rifabutin to the effective meds (though important to assess drug-drug interactions): https://gmodestmedblogs.blogspot.com/2022/06/h-pylori-rifabutin-based-therapy.html.  this rifabutin study used triple therapy with amoxicillin 3g, omeprazole 120mg and rifabutin 150mg (all divided into q8h dosing), though another study found that the results of double therapy were non-inferior to triple therapy: https://www.gastrojournal.org/article/S0016-5085(22)00609-6/fulltext

so, though the new recommendations for H Pylori treatment do suffer (in my opinion) from several concerns noted above, i think it is important to have them widely published to reinforce the importance of H Pylori again, the most common chronic bacterial infection in the world:

-- H pylori is a clear carcinogen associated with gastric cancer and, more rarely, MALT lymphoma, and it seems with colon cancer if the VacA variant of H Pylori

-- it has a slew of other associated illnesses, several of them quite severe

-- these associations are true whether the person has symptomatic or asymptomatic H Pylori infections, including in people taking aspirin or NSAIDs

-- therefore, the only way to prevent or treat these problems is by doing universal testing, including in the US given the data on the pretty high prevalence of H Pylori here

-- we do have an array of successful treatments that all require 14 days of therapy, though the one chosen can well be based on known resistance patterns in different communities, or if patients are from countries with known resistance patterns

    -- clarithromycin is in fact a very strong anti-H Pylori antibiotic but does have significant resistance in many areas. but, of note, there are regimens (sequential therapy) that work well with known clarithromycin resistance

-- and there is a pretty simple stool antigen test to detect H Pylori

geoff

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