Antimicrobial Stewardship for Helicobacter Pylori

Yesterday, this blog discussed what is needed to achieve high cure rates for H pylori. One of my microbiology colleagues informed me that until recently there have only been susceptibility standards for clarithromycin from the Clinical Laboratory Standards.  Now, the European Committee on Antimicrobial Susceptibility Testing has criteria for clarithromycin, tetracycline, amoxicillin, levofloxacin, metronidazole, and rifampin. Given the difficulty culturing H pylori, his view is that stool testing is the most promising avenue for susceptibility testing because we now have the genes that determine resistance delineated for all of these drugs.

A related issue is antimicrobial stewardship: DY Graham. J-M Liou. Clin Gastroenterol Hepatol 2022; 20: 973-983. Open Access: Primer for Development of Guidelines for Helicobacter pylori Therapy Using Antimicrobial Stewardship

Key points:

  • “Therapies that fail to achieve at least a 90% cure rate should be abandoned as unacceptable”
  • “Antibiotics in the access group have lower resistance potential … They should be widely available and affordable. Amoxicillin, tetracycline, and metronidazole are classified as the access group. In contrast, clarithromycin and levofloxacin have higher resistance potential and are classified as the watch group. They should be prioritized as key targets of stewardship program and monitoring”
  • “Therapies that contain antibiotics which do not contribute to outcome should be eliminated”
  • The “full antisecretory activity of PPIs requires 3–4 days. This makes the actual duration of effective therapy shorter than the days it is administered…However, pharmaceutical companies often have chosen to shorten the recommended duration of therapy to obtain a marketing advantage at the expense of reduced effectiveness”
  • “Currently most H pylori infections receive empiric therapy, and the clinician does not know or even have access to treatment guidance based on local or regional antimicrobial susceptibility patterns…few hospitals or clinics offer susceptibility testing”
  • Even without susceptibility testing, clinicians could achieve much better results if test of cure data were carefully collected and analyzed
  • “Metronidazole-containing bismuth quadruple therapy is unique in that it appears that metronidazole resistance can be partially or completely overcome by increasing the dose and duration of therapy…metronidazole resistance as assessed in vitro does not correlate well with its effectiveness in vivo, especially when used as a component of a triple or quadruple therapy”

H pylori is difficult to eradicate:

  • Location: “the organisms reside within the highly acid stomach, which is physically outside of the body and thus poorly accessible to blood-borne antibiotics and the immune system”
  • Inoculum effect: “H pylori is also typically present in vast numbers, resulting in an inoculum effect … the inoculum effect is largely responsible for the failure of dual therapy with PPIs clarithromycin, metronidazole, or levofloxacin, as their effectiveness is undermined by emergence of resistance during therapy”
  • Biofilm and intracellular: “A proportion of H pylori attach to the surface of gastric cells, leading to a biofilm phenomenon, and some are present intracellular by requiring the use of antibiotics capable of penetrating into cells”
  • Dormant state: “H pylori can become dormant in part because they can replicate only when the pH is approximately 6…this results in a persister effect”

My take: The lack of action on H pylori susceptibility despite the current tools is a bad look for the GI community. Would this still be the case if the treatment were relegated to our infectious disease colleagues? Antibiotic stewardship is coming for H pylori -children and adults with this infection should have higher cure rates and easier treatment regimens.

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