By Carol A. Kemper, MD, FACP

Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center

Dr. Kemper reports no financial relationships relevant to this field of study.

SOURCE: Siddique O, et al. Helicobacter pylori infection: An update for the internist in the age of increasing global antibiotic resistance. Am J Med 2018;131:473-479.

Like every other infection, Helicobacter pylori (HP) is increasingly drug resistant. Estimated failure rates are 5-10%, even after receipt of two different antimicrobial regimens. Failures most often are due to resistance to clarithromycin (which may be as high as 30% in some countries and in some parts of the United States) and levofloxacin (which also may be approaching resistance rates of 30% in some parts of the United States). Physicians need to keep pace with the consequences of this development and newer recommendations. Although the prevalence of HP seems to be decreasing in the United States, at least in higher socioeconomic strata, HP remains a problem for lower-income groups, travelers to developing countries, and the rest of the world. The prevalence of HP is believed to be > 50% in some parts of the world, especially in Central Asia, Central America, and Eastern Europe.

There are multiple barriers to appropriate testing and treatment. The first barrier is the promotion of testing for HP in patients at risk. HP screening is indicated for anyone with recurring epigastric discomfort, chronic use of nonsteroidal anti-inflammatory drugs, unexplained iron deficiency anemia, and ITP. Any of the “alarm symptoms,” such as recurrent vomiting, weight loss, and dysphagia, especially with a family history of gastric cancer, should prompt endoscopy with biopsy and examination for HP.

The second barrier is the type and timing of testing. Tests for active infection include stool antigen testing and the urea breath test (both ≥ 95% sensitive, ≥ 95% specific). But these tests must be performed more than four weeks after the use of any bismuth-containing product or antibiotic, and all proton pump inhibitors (PPI) must be stopped for more than two weeks. Serologic testing is not recommended, as it may remain positive for many years after successful eradication and is associated with a higher false-positive rate.

When selecting a first-line regimen, the patient should be queried about antibiotic use in the past one to two years. Prior treatment with macrolides or levofloxacin may increase the risk of resistance, and a regimen without the respective agent should be selected. In contrast, resistance to amoxicillin, tetracycline, and metronidazole is uncommon (< 2%).

Patients should be counseled that strict adherence to the regimen is necessary. Missed doses may increase the risk of developing resistance during treatment, especially with clarithromycin. Completion of the entire regimen is important to successful eradication. In those who fail a first-line regimen, consider whether the patient is allergic to penicillin and whether clarithromycin or levofloxacin was used in the first regimen. There are two or three options depending on the answers to these questions. For example, for patients who fail a first-line regimen containing clarithromycin, a regimen without clarithromycin should be selected (e.g., amoxicillin, levofloxacin, PPI × 14 days). The management of patients who have failed two regimens is not straightforward. Endoscopy with biopsy and culture for susceptibility testing is recommended, although the organism does not always grow well in culture, and susceptibility testing is not widely available. Empiric treatment with a nonclarithromycin-based regimen (e.g., rifabutin, amoxicillin, PPI × 10 days) in those previously treated with clarithromycin can be attempted. A levofloxacin-containing regimen can be used in those not previously treated with fluoroquinolones. Increasing the dose of the PPI, or using newer, more potent PPIs, may be helpful. Finally, confirming eradication four weeks or more following completion of treatment is mandatory.