Expires: March 16, 2023
Robin Patel, M.D.
Chair, Division of Clinical Core Laboratory Services
Professor of Laboratory Medicine and Pathology
Mayo Clinic, Rochester, Minnesota
Contact us: firstname.lastname@example.org.
Transcript and References
Hi, I’m Bobbi Pritt, Director of the Clinical Parasitology Lab and Vice Chair of Education in the Department of Laboratory Medicine and Pathology at Mayo Clinic. In this month’s “Hot Topic,” my colleague, Dr. Robin Patel, will discuss the diagnosis of Helicobacter pylori infection in an era of antimicrobial resistance. I hope you enjoy this month’s Hot Topic, and I want to personally thank you for allowing Mayo Clinic the opportunity to be a partner in your patient’s health care.
Helicobacter pylori: Bacteriology
Helicobacter pylori is a slender, curved urease-producing Gram-negative bacillus that is found in the mucosa of the stomach. It grows slowly in culture, requiring microaerophilic conditions. Helicobacter pylori is classified by the World Health Organization as a group one carcinogen due to its association with gastric carcinoma.
Helicobacter pylori: Clinical Presentation
The clinical presentation of Helicobacter pylori infection is varied, with many harboring this bacterium being asymptomatic. The microorganism is, however, associated with gastric and duodenal peptic ulcer disease, nonulcer dyspepsia, gastric carcinoma and gastric mucosa-associated lymphoid tissue lymphoma, also known as MALT lyphoma, MALToma or marginal zone B-cell lymphoma of MALT type.
Helicobacter pylori: Indications for Testing1
Testing for Helicobacter pylori is recommended in patients with peptic ulcer disease, gastric cancer, or gastric mucosa–associated lymphoid tissue lymphoma. Other recommended indications for testing include dyspepsia, prolonged use of nonsteroidal anti-inflammatory drugs or aspirin, unexplained iron-deficiency anemia, and immune thrombocytopenia.
Helicobacter pylori: Treatment2
Helicobacter pylori is typically treated with combinations of antibiotics along with a proton pump inhibitor. Detailed treatment guidance is beyond the scope of this Hot Topic. According to the guideline from the American College of Gastroenterology, an “…initial course of eradication therapy … generally offers the greatest likelihood of treatment success. Thus, careful attention to the selection of the most appropriate first-line eradication therapy for an individual patient is essential.” The guideline further states that, “The main determinants of successful Helicobacter pylori eradication are the choice of regimen, the patient’s adherence to a multi-drug regimen with frequent side effects, and the [susceptibility] of the Helicobacter pylori strain to the combination of antibiotics administered.”
Antimicrobial resistance in Helicobacter pylori is a rising challenge.
Susceptibility of 413 Helicobacter pylori Isolates, Mayo Clinic Laboratories3
Resistance can occur to any of the antibiotics used to treat Helicobacter pylori.
We reported on the susceptibility of 413 Helicobacter pylori isolates tested at Mayo Clinic Laboratories to amoxicillin, ciprofloxacin, clarithromycin, metronidazole and tetracycline. The rate of clarithromycin resistance was 70%.
Genetic Mechanisms of Clarithromycin Resistance, 111 Helicobacter pylori Isolates, Mayo Clinic Laboratories3
111 Helicobacter pylori isolates underwent 23S ribosomal RNA gene sequencing to define mutations associated with clarithromycin resistance. Overall, there was concordance between phenotypic susceptibility and genotypic results in 106, or 95% of the isolates. Of the 111 isolates, 23 were susceptible and 88 resistant to clarithromycin by phenotypic susceptibility testing. An A2143G mutation was found in 70 resistant isolates, an A2142G mutation in 12, and an A2142C mutation in 3. There was discordance between phenotypic susceptibility and genotypic results in 5 of the 111 isolates, with 3 having a resistant phenotype but a wild-type sequence, and 2 having a susceptible phenotype but an A2143G mutation.
Helicobacter pylori: Diagnosis
Non-invasive and invasive tests are available to diagnose Helicobacter pylori infection.
Non-invasive tests include stool PCR or antigen tests and a breath test where radiolabeled urea is ingested, and radiolabeled carbon dioxide (CO2) is measured in exhaled breath.
Serologic testing for Helicobacter pylori is no longer recommended.
Invasive tests involve endoscopy with biopsy. Biopsy material can be directly tested with a rapid urease test stained to examine for microorganisms consistent with Helicobacter pylori, and/or cultured to recover an isolate of Helicobacter pylori, which is then subjected to amoxicillin, levofloxacin, clarithromycin, metronidazole and tetracycline susceptibility testing.
Traditionally, the only way to define antimicrobial susceptibility has been by endoscopically collecting a biopsy for culture. Today, however, stool can be tested by a PCR assay that detects Helicobacter pylori and defines susceptibility based on interrogating the three 23S ribosomal RNA gene mutations most commonly associated with clarithromycin resistance—that is A2143G, A2142G, and A2142C. Isolates can also be tested with this PCR assay.
This slide shows a gastric biopsy demonstrating Helicobacter pylori by immunostaining and H&E staining.
Culture and Susceptibility Testing
This slide illustrates Helicobacter pylori culture and susceptibility testing. On the left, an agar plate growing Helicobacter pylori is shown. The images on the right show agar dilution antimicrobial susceptibility testing of Helicobacter pylori, including a growth control plate on the top, and a plate containing clarithromycin on the bottom.
Helicobacter pylori Diagnostic Algorithm
A proposed diagnostic algorithm for Helicobacter pylori is shown. For patients suspected of having Helicobacter pylori infection, endoscopy with biopsy is recommended if they are 60 years or older, or if there is a family history of proximal gastrointestinal cancer, previous malignancy of the esophagus or stomach, unexplained iron-deficiency anemia, a palpable mass or lymphadenopathy, melena, dysphagia, hematemesis, anemia, gastrointestinal bleeding, odynophagia, persistent vomiting or unintentional weight loss. Histology (with or without rapid urease testing) should be performed on the biopsy material with consideration given to performing Helicobacter pylori culture and susceptibility. If positive, the patient should be treated for Helicobacter pylori infection. Consideration should be given to performing Helicobacter pylori PCR with clarithromycin resistance prediction on stool to predict clarithromycin susceptibility or resistance if culture and susceptibility testing is not done on the biopsy material.
If the patient does not qualify for endoscopy, the preferred test is Helicobacter pylori PCR with clarithromycin resistance prediction performed on stool, with alternative tests being stool antigen testing, or, for those age 3 to 59 years, a Helicobacter pylori breath test. If either a stool antigen or a breath test is positive, consideration should be given to performing Helicobacter pylori PCR with clarithromycin resistance prediction on stool.
If the stool PCR assay is positive and predicts the absence of clarithromycin resistance, a clarithromycin-containing treatment regimen may be used. Conversely, if the stool PCR assay predicts clarithromycin resistance, a non-clarithromycin-containing treatment regimen should be used, with consideration given to endoscopy with biopsy for culture, and antimicrobial susceptibility testing to define the ideal treatment regimen.
In summary, antimicrobial resistance in Helicobacter pylori is rising. Therefore, consideration should be given to assessing for Helicobacter pylori antimicrobial susceptibility in patients testing positive for Helicobacter pylori. Stool PCR with prediction of clarithromycin susceptibility provides an option in this regard, as does endoscopy with biopsy for culture and susceptibility testing.
- Crowe S. Helicobacter pylori infection. N Engl J Med 2019 March;380:1158-65
- Chey W, Leontiadis G, Howden C, Moss S. ACG clinical guideline: Treatment of Helicobacter pylori infection. Am J Gastroenterol 2017 Feb; 112:212–238
- Chen D, Cunningham S, Nicolynn C, et al: Phenotypic and molecular antimicrobial susceptibility of Helicobacter pylori. Antimicrob Agents Chemother 2017 Apr;61:e02530-16