Transitioning of Helicobacter pylori Therapy from Trial and Error to Antimicrobial Stewardship

Abstract

Helicobacter pylori is the only major infection for which antimicrobial therapy is not designed using the principles of antimicrobial stewardship. Traditionally, antimicrobial therapy is a susceptibility-based therapy, achieves high cure rates, and includes surveillance programs to regularly provide updated data regarding resistance, outcomes, and treatment guidelines. Current H. pylori therapies identified by trial-and-error, and treatment recommendations and guidelines are based on comparisons among regimens that rarely take into account the prevalence or effect of resistance. The majority of patients currently treated achieve suboptimal results. A paradigm shift is required to abandon current approaches and embrace antimicrobial stewardship, and therefore reliably achieve high cure rates; develop, propagate, and update best practice guidelines; and provide surveillance of local or regional susceptibility/resistance patterns. These also require timely updates to clinicians regarding the current status of resistance, antimicrobial effectiveness, and ways to prevent antimicrobial misuse to extend the useful life of currently available antibiotics. Here, we discuss the differences among current approaches to H. pylori therapy and antimicrobial stewardship and identify what is required to achieve the transition. Conceptually, the differences are significant, and the transition will likely need to be both abrupt and complete. Recommendations for therapy during the transition period are given.

Primer for Development of Guidelines for Helicobacter pylori Therapy Using Antimicrobial Stewardship

“…The primary approach to development of management guidelines for H pylori therapy has been based on comparisons of differences between therapies (ie, a "better than" approach) with little regard for the absolute cure rates obtained. 4 In contrast, the principles of antimicrobial stewardship judge therapies primarily on their ability to reliably achieve prespecified cure rates. Antimicrobial stewardship is often a new concept to gastroenterologists, who are most familiar with treatment of diseases in which curative therapies are not available, treatment response is moderate, and placebo responses to therapy are common.…”

“…Fundamentally, antimicrobial stewardship can be considered as a coherent set of actions that (1) promote using antibiotics responsibly, (2) are designed to improve and measure appropriate use of antimicrobial agents and promote selection of optimal drug regimes, and (3) promote using antimicrobials in ways that ensure sustainable access to effective therapy for all that need them. 2,4 Here, we attempt of provide a primer to assist in what will likely prove to be a difficult transition to guidelines based on the principles of antimicrobial stewardship.…”

Classification system forHelicobacter pyloritherapies: Compared and contrasted to traditional infectious disease therapy

“…The treatment parameters such as doses, dosing intervals, and duration of therapy were not identified experimentally by formal optimization but rather were arbitrary or reflected marketing decisions rather than being evidence based. 3 overcome resistance as assessed in vitro. 5,6 Proof that metronidazole was required for effectiveness was examined by testing the effectiveness of the regimen without metronidazole which resulted in a marked drop in effectiveness.…”

“…Helicobacter pylori therapies did not follow the general paradigm of development describe above as most were developed by trial and error. The treatment parameters such as doses, dosing intervals, and duration of therapy were not identified experimentally by formal optimization but rather were arbitrary or reflected marketing decisions rather than being evidence based 3 . Most H. pylori therapies are prescribed empirically without the benefit of updated knowledge of local or regional susceptibility testing.…”

“…Type D therapies include at least one antimicrobial that do not contribute to cure of the infection and thus likely contribute to global antimicrobial resistance. Examples of Type D therapies are regimens containing three antimicrobials such as amoxicillin plus metronidazole and clarithromycin such as concomitant therapy or vonoprazan amoxicillin clarithromycin therapy which are responsible for 10's of thousands of kilograms of excess antimicrobial use per million treatments 3,4 …”