For patients who do not respond to an eradication regimen for Helicobacter pylori, susceptibility testing is not necessarily the next step, even for those presumed to be adherent to treatment, according to a new clinical practice update from the American Gastroenterological Association.
The update includes 12 best-practice statements, many of which involve steps to optimize selection of subsequent therapy (Gastroenterology 2021;160[5]:1831-1841). For several reasons, patients who fail an initial regimen should receive an empirical trial of an appropriately tailored second regimen instead of going directly to susceptibility testing.
A main driver of the update was evidence that the proportion of patients failing an eradication regimen for H. pylori is increasing. In addition to the best- practice statements, the document provides an algorithm to guide a systematic approach for increasing the likelihood of successful treatment.
The goal is to “optimize the selection of subsequent therapy so that fewer attempts are needed for successful eradication,” said Shailja C. Shah, MD, of the gastroenterology section at the VA San Diego Healthcare System, and lead author of the update. Dr. Shah said steps to reduce the risk for another treatment failure come after verifying the patient has been adherent to treatment and received adequate suppression of gastric acid.
The practical reason for shifting away from reliance on susceptibility testing in the new update involves the challenges of testing, such as the many chances for delays and errors in the process. Interpreting and applying in vitro results to clinical practice is not necessarily straightforward, she said.
“To this end, susceptibility testing has not been demonstrated as a superior tool for guiding selection of more effective therapy in patients with refractory H. pylori,” Dr. Shah said. In the update, the authors note that therapies selected on the basis of previous exposure to antibiotics are as effective as selecting on the basis of susceptibility testing.
Resistance is the usual cause of refractory H. pylori infection, but the recommendations call for improving the likelihood of eradication not only by avoiding regimens likely to fail but by addressing common reasons for nonadherence. Clinicians now are advised to alert patients to potential side effects of medications and educate them about the rationale for adherence to dosing instruction.
Other best-practice statements outline the value of being familiar with local data regarding eradication success with specific regimens and considering the patient’s earlier exposure to the antibiotics under consideration. For example, recent exposure to macrolides or fluoroquinolones provides a rationale for considering alternative drug classes. The authors suggest levofloxacin- or rifabutin-based triple therapies as an alternative when bismuth quadruple therapy is ineffective.
Clinicians should not overlook the importance of adequate dosing of antibiotics, such as metronidazole or amoxicillin, or proton pump inhibitors, as factors to avoid treatment failure, according to other statements in the update. One issue for PPIs specifically is that most are metabolized by the cytochrome P450 2C19 (CYP2C19) isoenzyme, which can be a source of inadequate acid suppression in genetically rapid metabolizers.
When there is concern about inadequate acid suppression, the update recommends approaches such as using a PPI not metabolized by CYP2C19, twice-daily PPI dosing or switching to a potassium-competitive acid blocker.
In patients who have failed a seven-day regimen, subsequent regimens of 10 to 14 days should be considered, according to the update.
William D. Chey, MD, a professor of gastroenterology and nutrition sciences at the University of Michigan Medical School, in Ann Arbor, reiterated the premise that susceptibility testing should not be considered an early strategy following failure of the first eradication regimen.
“We made a very similar recommendation in the ACG [American College of Gastroenterology] guidelines published in 2017,” said Dr. Chey, who led that effort. The concern was lack of evidence of practicality and cost-effectiveness.
Rather than moving quickly to susceptibility testing, “the key is to understand the reliable regimens” in refractory patients, according to Dr. Chey. Currently, he favors bismuth quadruple therapy and rifabutin triple therapy, but he noted recent evidence that vonoprazan triple therapy might be another effective option.
—Ted Bosworth
Dr. Chey reported financial relationships with several pharmaceutical companies that have products for treatment of gastroenterological diseases. Dr. Shah reported no relevant financial disclosures.
This article is from the July 2021 print issue.