Antimicrobial resistance is the most common cause of treatment-refractory Helicobacter pylori infection, but before switching antibiotics, clinicians should screen for factors such as treatment nonadherence or inadequate suppression of gastric acid, according to a clinical practice update from the American Gastroenterological Association.
Dr. Shailja C. Shah
“Inadequate acid suppression is associated with H. pylori eradication failure. The use of high-dose and more potent PPIs, PPIs not metabolized by CYP2C19, or potassium-competitive acid blockers, if available, should be considered in cases of refractory H. pylori infection,” wrote Shailja C. Shah, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tenn., and coauthors Prasad G. Iyer, MD, and Steven F. Moss, MD. . Their report is in Gastroenterology.
H. pylori infection is the most common cause of gastric cancer. Although eradication is widely recommended, it can be challenging because of strain diversity, rising antimicrobial resistance, a dearth of recent head-to-head clinical trials, and sparse epidemiologic and sensitivity data, the experts noted. For this reason, before selecting an eradication regimen, it is vital to thoroughly review a patient’s history of antibiotics – for example, any prior macrolide or fluoroquinolone exposure should preclude the use of clarithromycin- or levofloxacin-based regimens “given the high likelihood of resistance,” the experts wrote. They also advised that clinicians should avoid levofloxacin unless the H. pylori strain is known to be sensitive to it or if population rates of levofloxacin resistance rates are known to be less than 15%. However, amoxicillin, tetracycline, and rifabutin resistance are rare, and these agents “can be considered for subsequent therapies in refractory H. pylori infection.”
A longer antimicrobial regimen (such as 14 vs. 7 days) is more likely to eradicate H. pylori. If first-line bismuth quadruple therapy (such as a PPI plus bismuth, metronidazole, and tetracycline) fails, then second-line options include another bismuth-containing quadruple-agent regimen, or triple therapy with rifabutin or levofloxacin plus high-dose dual PPI therapy and amoxicillin. If patient history contains “penicillin allergy” but does not list anaphylaxis, then penicillin allergy testing can help determine if amoxicillin-based regimens are an option. The authors also note that, when used, amoxicillin should be dosed at 2 g/day in divided doses three to four times per day in order to avoid low trough levels because this might be associated with H. pylori eradication failure. For metronidazole, regardless of in vitro resistance, eradication is more likely if patients receive 1.5-2 g/day, in divided doses, with concomitant bismuth.
Treatment nonadherence contributes to refractory H. pylori infection and may be caused by the complexity of the treatment regimen, high pill burden, and side effects. To improve adherence, the experts advised counseling patients on the rationale for the treatment regimen, the dosing instructions, the importance of completing the full course of therapy, and providing anticipatory guidance regarding common side effects. If a patient adheres to second-line treatment and it still fails, then susceptibility testing is advised before starting another regimen. Depending on the results, options may include levofloxacin-based quadruple therapy, another round of bismuth-based quadruple therapy, a PPI plus amoxicillin and rifabutin, or high-dose PPI therapy plus high-dose amoxicillin (2-3 g/day divided across three to four doses).
Other considerations include how to approach patients and caregivers, particularly the elderly and other vulnerable patients, with shared decision-making to help them weigh the potential benefits of continuing to try to eradicate H. pylori against the risk of possible adverse effects and the “inconvenience of repeated exposure to antibiotics and high-dose acid suppression,” the experts wrote. They also advised tracking rates of eradication success and relevant demographic and clinical data, including patients’ antibiotic history. Publicly sharing aggregated, deidentified results can help other local clinicians select eradication regimens. Finally, the use of probiotics and other adjunctive therapies “should be considered experimental” since these have no clear benefit for treating refractory H. pylori infection.
Dr. Shah was funded by an AGA Research Scholar Award and a Veterans Affairs Career Development Award. She reported having no conflicts of interest. Dr. Iyer and Dr. Moss disclosed ties to Exact Sciences, Pentax Medical, Redhill Biopharma, Phathom, American Molecular Laboratories, and Takeda.