Approach Considerations
Selected 2021 American Gastroenterological Association (AGA) best practices
Antibiotic resistance is typically the cause of refractory H pylori infection (ie, persistent infection following attempted eradication therapy). [12] Try to ascertain potential contributing causes, such as inadequate adherence to therapy and insufficient gastric suppression.
Thoroughly review prior antibiotic exposures. [12] In the setting of any history of treatment with macrolides or fluoroquinolones, avoid clarithromycin- or levofloxacin-based regimens, respectively, owing to the greater possibility of resistance. However, consider amoxicillin, tetracycline, and rifabutin as subsequent therapies in refractory H pylori infection as resistance to these antibiotics is rare.
Adjunct therapies, including probiotics, have been proposed, but they are considered experimental as their benefits remain unproven for treating refractory H pylori infection. [12]
2020 World Society of Emergency Surgery (WSES) guidelines
Perforated and bleeding peptic ulcer clinical practice guidelines were released in January 2020 by the WSES. Indications for antimicrobial therapy and for H pylori testing in patients with bleeding peptic ulcer are as follows [16] :
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Empirical antimicrobial therapy not recommended
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H pylori testing in all patients
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If positive for H pylori, eradication therapy recommended
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First-line eradication therapy: Standard triple therapy (ie, amoxicillin, clarithromycin, proton-pump inhibitor [PPI])
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First-line therapy if high clarithromycin resistance detected: Ten-day sequential therapy with four drugs (ie, amoxicillin, clarithromycin, metronidazole, PPI)
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Second-line therapy if first-line failed: Ten-day levofloxacin-amoxicillin triple therapy
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Start standard triple therapy after 72-96 hours of intravenous PPI, for 14-day duration
Medical Care
Only treat patients who have a positive test result for H pylori infection. The optimal timing of H pylori eradication in asymptomatic persons is during the period when the mucosal damage remains nonatrophic. [1]
Carefully educate patients regarding the importance of completing the prescription and about the potential adverse effects of the medications. [1, 12] Importantly, consider possible antibiotic resistance when selecting the treatment regimen. Note that surgery is not required for patients with H pylori infection, but it may be considered in patients with severe complications, such as cancer.
The US Food and Drug Administration has approved several regimens, which are accepted internationally, for the treatment of H pylori infection in patients with peptic ulcer disease, both gastric and duodenal. These regimens are also known as triple therapies and have reported cure rates from 85% to 90%. Unfortunately, with the increasing rise in antimicrobial resistance, there has been an associated increase in the failure rate of standard triple therapy for H pylori infection. [17] Thus eradication regimens should be based on the best locally effective regimen, optimally with the use of individual susceptibility testing or community antibiotic susceptibility, or data regarding antibiotic use and clinical outcomes. [1, 18]
It is recommended that the outcome of eradication therapy (test for cure) always be evaluated, with noninvasive means preferred. [1]
Macrolide resistance in patients with H pylori infection is an important problem. Although the molecular mechanisms of nitroimidazole resistance are very complex and still unclear, resistance has been shown to be due to a single point mutation (usually in the RDXA gene, although other genes may also be involved, eg, FRDXA) in 1 of 4 positions of the bacterial 23S rDNA. Such mutations also determine cross-resistance to other macrolides.
2021 American Gastroenterological Association (AGA) recommendations
As noted earlier, the American Gastroenterological Association (AGA) advises that in the setting of any history of treatment with macrolides or fluoroquinolones, avoid clarithromycin- or levofloxacin-based regimens, respectively, because of the higher risk of resistance. [12] Consider amoxicillin, tetracycline, and rifabutin as subsequent therapies in refractory H pylori infection as resistance to these antibiotics is rare.
The AGA advises that if first-line therapy with bismuth quadruple therapy is ineffective, clinicians and patients should jointly decide on the selection of second-line options between (a) levofloxacin- or rifabutin-based triple-therapy regimens with a high-dose dual proton pump inhibitor (PPI) and amoxicillin, and (b) an alternative bismuth-containing quadruple therapy. [12]
When using metronidazole-containing regimens, consider adequate dosing of metronidazole (1.5–2 g daily in divided doses) with concomitant bismuth therapy to improve success of eradication therapy.
If there is no history of anaphylaxis, consider penicillin allergy testing in patients who have been labeled as having this allergy to delist penicillin as an allergy and potentially enable its use. Use amoxicillin at a daily dose of at least 2 g divided three or four times per day to avoid low trough levels.
Because inadequate acid suppression is associated with H pylori eradication failure, consider using high-dose and more potent PPIs, PPIs not metabolized by CYP2C19, or potassium-competitive acid blockers, if available, in patients with refractory H pylori infection.
Higher eradication success is achieved with longer treatment durations relative to those of shorter durations (eg, 14 days vs 7 days). Thus, as appropriate, choose longer treatment durations for treating refractory H pylori infection.
Shared decision making regarding ongoing attempts to eradicate H pylori may be appropriate in some settings. Carefully evaluate the potential benefits of H pylori eradication against potential adverse effects and the inconvenience of repeated antibiotic exposure and high-dose acid suppression, particularly in vulnerable populations (eg, elderly).
In the setting of two failed therapies with confirmed patient adherence, consider H pylori susceptibility testing to guide the selection of subsequent regimens.
It is essential to collect local data on H pylori eradication success rates for each regimen, as well as patient demographic and clinical factors (including prior non-H pylori antibiotic exposure). Make aggregated data publicly available to guide local selection of H pylori eradication therapy.
Other considerations
An emerging and increasing problem in many Western countries is the fact that some H pylori strains in children are resistant to the antibiotic clarithromycin. [19] The causes are not known.
All the eradication treatments have a high incidence of certain adverse effects (eg, nausea, metallic taste). If skin rash, vomiting, or diarrhea occurs, discontinue the treatment.
The links between H pylori and nonulcer dyspepsia are debated; however, some patients with nonulcer dyspepsia benefit from eradication. Indeed, H pylori eradication is the first-line and preferred treatment for H pylori -infected dyspeptic individuals. [1] Patients with symptoms have a higher eradication rate than patients with nonulcer dyspepsia disease. Eradication of H pylori in patients without peptic ulcer disease has resolved the dyspepsia in a few cases. If successful H pylori eradication does not resolve dyspeptic symptoms, patients should be considered to have "functional dyspepsia." [1]
Diet and activity
No dietary restrictions are usually needed, and no limitations of physical activity are needed if patients do not have complications.
Posttreatment monitoring
Consider performing a urea breath test (UBT) 4-12 weeks after the end of treatment. An esophagogastroduodenoscopy (EGD) with biopsy and a urease test also may be useful, but, importantly, remember that this test does have a significant rate of false-negative results.
Prevention
Searching and screening for H pylori gastritis depends on the epidemiologic setting and is appropriate at an age before the onset of atrophic gastritis and intestinal metaplasia. [1]
Note that the risk of gastric cancer is increased in patients who have an H pylori infection and whose first-degree relatives have a history of gastric cancer, even if they are asymptomatic. Thus, eradicating H pylori reduces the risk of gastric cancer; the risk reduction relies on the presence, severity, and extent of atrophic damage at the time of eradication. [1]
Persons emigrating from geographic areas with a high incidence of gastric cancer have an increased risk.
Consider any patient with precancerous lesions of the stomach (ie, intestinal metaplasia) for treatment of H pylori infection.
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Helicobacter Pylori Infection. This image shows an antral gland of the stomach with a large Giemsa-stained colony of Helicobacter pylori in the lumen (arrow) at 250X power. Courtesy of Pantaleo Bufo, University of Foggia, Italy.
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Helicobacter Pylori Infection. A lamina propria of the stomach is shown with two mast cells overlapping each other. Note the upper part reveals the degranulating process with the release of granules of inflammation mediators (Giemsa staining, 250X). Courtesy of Pantaleo Bufo, University of Foggia, Italy.
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Helicobacter Pylori Infection. A transverse section of the gastric lamina propria is shown. In the lower part, an antral gland of the stomach is present with some Helicobacter pylori in the lumen (red-blue arrow). In the upper part, a mast cell (yellow arrow) is present (Giemsa staining, 250X). Courtesy of Pantaleo Bufo, University of Foggia, Italy.
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Helicobacter Pylori Infection. An antral gland of the stomach is shown with a large colony of Helicobacter pylori in the lumen (Giemsa staining, 425X). Courtesy of Pantaleo Bufo, University of Foggia, Italy.
